The management of prostate cancer has posed challenges for clinicians in determining optimal treatment strategies. Over the years, various radiopharmaceuticals have been utilized for both the diagnosis and treatment of the prostate cancer. Recent advancements in prostate specific membrane antigen (PSMA) based imaging have enabled the early and precise detection of local recurrence, lymph nodes or distant metastases, resulting a paradigm shift, which significantly influenced clinical decision making. Moreover, PSMA targeted treatments, as a part of theranostic approach, have introduced novel treatment options for patients with castration resistant metastatic prostate cancer, who were previously limited to palliative treatment alternatives. The clinical integration of PSMA based imaging and treatment has led to the commencement of collaborative studies across multiple disciplines including radiation oncology. Radiopharmaceuticals led by PSMA have the potential to facilitate accurate treatment decision making through earlier and more precise lesion detection, as well as improve patient outcomes when combined with radiotherapy. We aimed to review the role of radiopharmaceuticals in diagnosis and treatment of prostate cancer, focusing on their utility in guiding radiotherapy and the potential benefits of combining these radiopharmaceuticals with radiotherapy.

68Ga-DOTA-FAPI-04 is a new positron imaging agent, and its application in bone metastasis has been limited. The purpose of this retrospective study was to compare the diagnostic ability of 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT to detect bone metastases in patients with different types of cancer.

A total of 293 patients with pathologically confirmed primary malignancies were examined with 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT within one week. Using pathological examination or follow-up CT or MRI scan as the gold standard, the diagnostic efficacy of the two methods in differentiating bone metastases was compared (p < 0.05, with statistical significance). The maximum standard uptake value (SUVmax) of the two methods for different types of bone metastasis was further compared. The SUVmax was used to compare the differences between the two methods in detecting bone metastases in different tumor types and different sites.

A total of 48 patients were diagnosed with bone metastasis, and 245 patients without bone metastasis. There were 376 bone metastases and 243 benign bone lesions. 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT detected 376 and 228 metastases, respectively. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) and accuracy of 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT were 100.0 % vs 60.6 %, 93.8 % vs 99.2 %, 96.2 % vs 99.2 %, 100.0 % vs 62.0 % and 97.6 % vs 75.8 %, respectively. Compared with 18F-FDG, 68Ga-DOTA-FAPI-04 uptake was significantly increased in both benign bone lesions and metastases (p = 0.001). The uptake of 68Ga-DOTA-FAPI-04 for osteoblastic metastasis was also significantly higher than that of 18F-FDG (p < 0.001). In bone metastasis of lung cancer and gastric cancer, 68Ga-DOTA-FAPI-04 uptake was higher than that of 18F-FDG PET/CT (p < 0.05). Using SUVmax = 4.1 and SUVmax = 6.2 as the cutoff value by 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT, it was possible to predict the occurrence of metastases (AUC = 0.817,95 % CI: 0.791-0.923 vs AUC =0.751,95%CI:0.626-0.875).

68Ga-DOTA-FAPI-04 as a novel imaging agent, can detect more bone metastases and has a higher tracer uptake level than 18F-FDG. Especially for lung and gastric cancer, 68Ga-DOTA-FAPI-04 PET/CT may be a more reliable means to detect bone metastases.

To assess the prognostic value of Fluorine 18-labeled fluorodeoxyglucose [18F]FDG, gallium 68-labeled fibroblast-activation protein inhibitor-04 [68Ga]Ga-FAPI-04, 11C-acetate in hepatocellular carcinoma (HCC) and evaluate the potential usefulness and advantages of different combinations for accurate diagnosis.

Thirty-six patients with suspected hepatic masses were prospectively enrolled from May 2021 to September 2022 and underwent [18F]FDG, [68Ga]Ga-FAPI-04, and 11C-acetate PET/CT scans before surgery. PET/CT results and histopathologic examinations were independently interpreted by two radiologists and pathologists, respectively. Kaplan-Meier overall survival curves were calculated and the sensitivity among [18F]FDG, 11C-acetate, [68Ga]Ga-FAPI-04, and different combinations were compared.

Of the 36 included patients (mean age, 59 years ± 10 (standard deviation)), 29 were diagnosed with HCC, four with non-HCC malignant tumors, and three with benign tumors. Patients with HCC lesions negative for 11C-acetate or [68Ga]Ga-FAPI-04 exhibited poorer overall survival. Out of 36 patients, 44 HCC lesions were detected. The dual-tracer [68Ga]Ga-FAPI-04/11C-acetate exhibited the highest sensitivity (39 of 44 lesions (88.6%)) among all schemes. HCC lesions with higher histological grade and microvascular invasion (MVI) showed higher maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of [18F]FDG, but no evidence of significant differences was found in [68Ga]Ga-FAPI-04 and 11C-acetate PET/CT. Higher expression of fibroblast activation protein (FAP) showed higher uptake of [68Ga]Ga-FAPI-04 and [18F]FDG.

[68Ga]Ga-FAPI-04 and 11C-acetate PET/CT exhibited good predictive value for HCC patients, with their combination showing the highest sensitivity for HCC detection, suggesting potential for improved diagnostic protocols.

Question What are the prognostic and diagnostic values of PET/CT tracers, including [18F]FDG, [68Ga]FAPI-04, and 11C-acetate? Findings Hepatocellular carcinoma, with differing findings across [18F]FDG, [68Ga]GaFAPI-04, and 11C-acetate PET/CT, showed varied prognoses; [68Ga]GaFAPI-04 and 11C-acetate combined offered the highest detection sensitivity. Clinical relevance Evaluating the prognostic value and diagnostic efficacy of different tracer combinations in patients with hepatocellular carcinoma helps to guide the optimal selection of tracers in clinical practice.

Fibroblasts activated protein (FAP) appears to be a promising target for tumor theranostics. However, the development of radioiodinated probes for FAP has been slow. In this study, a progressive abumin-driven strategy was adopted to improve the FAP-targeted delivery of radioiodinated probes for tumor theranostics. A series of FAP-targeted probes (namely [131I]IPB-FAPI, [131I]IPB-FAPI-A1, [131I]IPB-FAPI-A3, [131I]FSDD3I) were synthesized by incorporating an albumin-binding moiety (4-(p-iodophenyl)butyric acid, 4-IPBA) labeled with radioiodine. The specificity and binding characteristics of the radiotracers to FAP and human serum albumin (HSA) were confirmed. SPECT imaging results showed that the [131I]FSDD3I had more prominent tumor retention property and superior target-to-nontarget ratio, which were consistent with the biodistribution results. As expected, the FAP-targeted therapy with 11.1 MBq [131I]FSDD3I significantly inhibited tumor growth. In conclusion, this proof-of-concept study employed a progressive design strategy to enhance pharmacokinetics of radioiodinated FAP-targeted probes. Among these radioiodinated FAPI probes, 131I-labeled FSDD3I ([131I]FSDD3I) emerged as a standout candidate with superior competitive advantages for application in radioiodine-guided internal irradiation therapy.

To compare the diagnostic value of [18F]ALF-NOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) and 18F-fluorodeoxyglucose (FDG) PET/CT in gastric cancer.

This single-center retrospective analysis included 65 patients with gastric cancer who received both [18F]FDG and [18F]ALF-NOTA-FAPI-04 PET/CT for initial staging or restaging. Histopathological manifestations, typical imaging manifestations, follow-up imaging, and comprehensive clinical assessment were used as reference criteria. The uptakes of [18F]FDG and [18F]ALF-NOTA-FAPI-04 PET were compared using the Wilcoxon signed-rank test. McNemar's test was employed to compare the diagnostic performance of the two imaging techniques.

A total of 65 patients were included (26 male and 39 female; mean age, 54.03 ± 10.41 years), Among them, 10 were newly diagnosed, 46 underwent radical gastrectomy, and 9 received only chemotherapy prior to the study. Compared with [18F]FDG PET/CT, [18F]ALF-NOTA-FAPI-04 PET/CT showed higher sensitivity in primary or recurrent tumors (100% vs. 64.52%, p < 0.001)), lymph node metastases (88.89% vs. 38.89%, p = 0.006), distant metastases (91.18% vs. 50%, p < 0.001). From the semi-quantitative evaluation, the Maximum standardized uptake value (SUVmax) and target-to-background ratio of [18F]ALF-NOTA-FAPI-04 PET/CT were significantly higher than that of [18F]FDG PET/CT in primary or recurrent tumors, lymph node metastases, and distant metastases (all p < 0.001).

Our study results indicate that [18F]ALF-NOTA-FAPI-04 PET/CT outperforms [18F]FDG PET/CT in the detection of primary or recurrent tumors, lymph node metastasis, and distant metastasis in gastric cancer.

Question Early diagnosis and precise staging of gastric cancer are crucial for patient prognosis; however, current imaging techniques still face significant limitations. Findings [18F]ALF-NOTA-FAPI-04 PET/CT demonstrated significantly higher sensitivity than [18F]FDG PET/CT in detecting primary or recurrent tumors and metastases in patients with gastric cancer. Clinical relevance [18F]ALF-NOTA-FAPI-04 PET/CT is an advanced imaging diagnostic technique that significantly enhances the diagnostic accuracy for gastric cancer and its metastatic lesions. This technology provides robust support for clinical decision-making, thereby improving the management of patients with gastric cancer.

Accurate diagnosis and staging of lung cancer are critical for optimal clinical management. Fibroblast activation protein inhibitor (FAPI) imaging has emerged as a promising modality with superior detection capabilities for lung cancer. We hypothesized that [1⁸F]FAPI-42 PET/CT would enhance diagnosis, TNM staging, and influence oncologic management in patients with suspected or confirmed lung cancer.

In this retrospective study, 155 patients with clinically suspected or confirmed lung cancer underwent both conventional imaging and [1⁸F]FAPI-42 PET/CT scans within a one-week interval, without any intervening treatment. Lesions were visually assessed and categorized to evaluate the diagnostic capability of [18F]FAPI-42 PET/CT. Tracer activity was quantified using maximum standardized uptake values (SUVmax) and tumor-to-background ratios. TNM staging was independently determined by a board-certified radiologist or nuclear medicine physician using both imaging modalities, and discrepancies were assessed. Changes in TNM staging were documented and evaluated for their impact on clinical management.

Of the 155 patients, 99 were evaluated for primary lesion diagnosis and staging. Pathological examination confirmed malignant tumors in 87 patients and benign tumors in 12. The diagnostic sensitivity and positive predictive value of [18F]FAPI-42 PET/CT for detecting primary lung tumors were 96.77% and 92.78%, respectively. Malignant lesions exhibited significantly higher SUVmax compared to benign lesions (5.2 vs. 1.5, P = 0.0002), with an area under the ROC curve of 0.87. In total, 1,556 malignant lesions were identified among patients with lung cancer, and [18F]FAPI-42 PET/CT demonstrated a diagnostic accuracy of 95.50%. However, its sensitivity for detecting adrenal metastases was lower at 33.33%, with a specificity of 100% and an accuracy of 53.85%. The use of [18F]FAPI-42 PET/CT resulted in changes in TNM staging for 46% of patients, leading to upstaging in 58 patients and downstaging in 5. These staging adjustments directly impacted clinical management in 34 patients, prompting modifications in treatment plans.

[18F]FAPI-42 PET/CT is a promising modality for lung cancer diagnosis and staging, demonstrating high sensitivity and specificity. Its use significantly altered TNM staging in nearly half of the patients, directly impacting oncologic management and treatment planning. However, its limited sensitivity for detecting adrenal metastases underscores the need for additional imaging techniques.

The role of fibroblast activation protein inhibitor (FAPI) PET CT scan is not well documented in papillary thyroid cancer (PTC) patients. Patients with radioiodine refractory PTC and high thyroglobulin levels need PET/CT scan which is generally done by 18F FDG. In the current study, the diagnostic performance of 68Ga FAPI and FDG PET/CT scans were compared head to head in patients with radioiodine refractory PTC.Fourteen patients with negative whole body Iodine scans and high thyroglobulin levels underwent whole body PET scans with, respectively, 120-310 and 145-370 MBq 68Ga FAPI-46 and 18F FDG. SUVmax of the back ground in the blood pool and liver and the hottest, largest and average neck, mediastinum, lung and bone lesions were calculated and compared.Ten patients had at least one active (SUVmax>blood pool) lesion similarly in two scans. The liver and blood pool SUVmax values were 1.25(0.2) and 1.7(0.2) in FAPI and 2.65(0.2) and 2.0(0.2) in FDG PET images, respectively. The difference was significant (p=0.001). Standard SUV of the hottest lesion to liver was above 3 in all FAPI scans but in half of FDG scans. Target lesion number and intensity were similar between two PET studies but in a patient out of 5 pulmonary metastatic patients, pulmonary nodules were negative (SUVmax=0.9) in FDG while positive (SUVmax= 3.8) in FAPI images (i.e. 20% patient upstaged).FAPI accumulates in the recurrent and metastatic lesions of patients with Iodine refractory PTC at least as well as FDG with particular privileges as lower injected activity and lower back ground.

To evaluate the diagnostic accuracy and clinical impact of fibroblast activation protein (FAP)-targeted PET/CT imaging in primary and metastatic breast cancer and compare the results with those of standard-of-care imaging (SCI) and [18F]FDG PET/CT.

We prospectively analyzed patients with diagnosed or suspected breast cancer who underwent concomitant FAP-targeted PET/CT (radiotracers including either [68Ga]Ga-FAPI-46 or [18F]FAPI-42) and [18F]FDG PET/CT scans from June 2020 to January 2024 at two medical centers. Breast ultrasound (US) imaging was performed in all treatment-naïve patients as SCI. The SUVmax, tumor-to-background ratio (TBR), lesion detection rate, and tumor-node-metastasis (TNM) classifications between FAP-targeted and [18F]FDG PET/CT were evaluated and compared.

Sixty-one female patients (median age, 52 y; range, 28-82 y) were included. Among them, 23 patients underwent evaluation for a definitive diagnosis of suspected breast lesions, 15 underwent initial staging, and 23 were evaluated for the detection of recurrence. The sensitivities of breast US, [18F]FDG, and FAP-targeted PET/CT for detecting primary breast tumors were 82%, 79%, and 100%, respectively. Regarding the diagnosis of recurrent/metastatic lesions, the lesion-based detection rate of FAP-targeted PET/CT was significantly higher than that of [18F]FDG, which included local and regional recurrence, neck lymph node (LN), abdomen LN, bone, and liver metastases. Compared with [18F]FDG PET/CT, FAP-targeted PET/CT altered thirteen patients' TNM staging/restaging (13/59, 22%) and nine patients' clinical management (9/59, 15%). Compared to SCI, FAPI changed fourteen patients' TNM staging/re-staging (14/59, 24%) and eleven patients' therapeutic regimens(11/59, 19%). There was no significant association between FAPI-derived SUVmax and receptor status/histologic type in both primary and metastatic lesions.

FAP-targeted PET/CT was superior to [18F]FDG in diagnosing primary and metastatic breast cancer, with higher radiotracer uptake and TBR, especially in the detection of primary/recurrent tumors, abdominal LN metastases, liver, and bone metastases. FAP-targeted PET/CT is superior to [18F]FDG and SCI in TNM staging and may improve tumor staging, recurrence detection, and implementation of necessary treatment modifications.

This pilot study compared the diagnostic performances of DSC-MRI and FAPI PET in differentiating tumor progression (TP) and treatment-related change (TRC) in isocitrate dehydrogenase (IDH) wild-type glioblastoma during follow-up.

IDH wild-type glioblastoma patients who underwent DSC-MRI and FAPI PET were analyzed retrospectively. TP and TRC lesions were confirmed through radiological and clinical follow-up, with a median follow-up period of 8 months (2-12 months). The differences in DSC-MRI (CBVmax, CBVmean, and rCBVmean) and FAPI PET (SUVmax, SUVmean, and TBR SUVmean) parameters between TP and TRC were compared. ROC curve analyses were performed to assess the diagnostic performance. DeLong's test evaluated the differences in AUCs.

Twelve patients (6 men and 6 women, aged 33-70) with IDH wild-type glioblastoma were enrolled. Totally 18 lesions (8 TRC and 10 TP) were detected. All DSC-MRI and FAPI PET parameters were significantly higher in the TP than in the TRC. CBVmean showed the highest diagnostic performance among all parameters. However, the DeLong test revealed no significant difference in diagnostic performance between DSC-MRI and FAPI PET parameters.

Although the CBVmean has excellent diagnostic performance in differentiating TP from TRC, FAPI PET parameters were statistically found to have similar diagnostic performance. FAPI PET may be an alternative modality for patients with IDH wild-type glioblastoma who are unable to undergo DSC-MRI. However, further prospective large cohort studies and clinical validation are necessary.

Liver fibrosis is a chronic fibrosing hepatic disorder following recurrent injury, characterized by the excessive accumulation of extracellular matrix. Early detection has a great clinical impact because 80-90% of hepatocellular carcinomas are known to develop in fibrotic or cirrhotic (end-stage fibrotic) livers. PET imaging with FAP ligands exhibited highly promising results in recent years to visualize fibrosis in various organs due to the crucial role of activated fibroblasts in fibrosing processes. However, still little is known about the efficacy of FAP imaging in liver fibrosis. Thus, we sought to investigate the potential of FAPI-PET in a cohort of oncological and non-oncological patients.

199 patients who underwent FAPI-PET/CT at the University Hospital of Heidelberg between July 2017 and July 2020 were retrospectively analyzed. The tracer uptake of the liver was analyzed and correlated with radiological and clinical parameters.

We observed a weak but significant negative correlation between the hepatic FAPI uptake and CT density (r = - 0.273, P < 0.001***). A positive correlation was observed between hepatic FAPI uptake and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) (r = 0.183, P = 0.009**), an established surrogate for liver fibrosis. The liver SUV (standardized uptake value) mean and SUVmax of FAPI showed significant differences between groups of patients with low (< 0.5), middle (0.5-1.0) and higher (> 1.0) levels of APRI (both P < 0.001***).

These preliminary observational results suggest that FAPI-PET may be a viable non-invasive method to asses liver fibrosis.

The aim of this study was to, evaluate the diagnostic accuracy of [⁶⁸Ga]Ga-FAPI-46 positron emission tomography (PET)/computed tomography (CT) in high-risk prostate cancer (PC) compared to [¹⁸F]PSMA / [⁶⁸Ga]Ga- PSMA- and [¹⁸F]FDG- PET/CT as well as multiparametric magnetic resonance imaging (MRI).

Ten patients with high-risk PC (PSA > 20 ng/mL, Gleason score > 7, or > T2c) underwent PET/CT imaging using [⁶⁸Ga]Ga-FAPI-46, [¹⁸F]F-/[⁶⁸Ga]Ga-PSMA and [¹⁸F]FDG before radical prostatectomy (RP). The maximum standardized uptake values (SUVmax) were measured for the entire prostate and individual prostate sextants. Diagnostic accuracy was assessed per patient and per segment by correlating imaging findings with final histopathologic results. Immunohistochemical analysis of PSMA and FAP expression was performed on the index tumor lesion.

Histopathologic analysis confirmed pT2c and pT3 prostate adenocarcinoma in 4 (40%) and 6 (60%) patients, respectively. One patient (10%) had regional lymph node metastasis (pN1). The International Society of Urological Pathology (ISUP) grade groups (GGs) were 2 (60%), 3 (20%), and 5 (20%). Overall, 46 of 60 prostate sextants were histologically positive for PC. While PSMA expression was detected in all patients, FAP expression was observed in 5 of 9 cases (55.5%). Per-patient and per-segment analyses demonstrated that [⁶⁸Ga]Ga-FAPI-46 and [¹⁸F]F-/[⁶⁸Ga]Ga-PSMA had comparable diagnostic accuracy and outperformed [¹⁸F]FDG. The mean (SD) SUVmax of the entire prostate was highest for PSMA PET/CT at 13.1 (7), followed by FAPI at 7.6 (5.5) and FDG at 5.4 (3.5) (p = 0.015). Among patients in the FAPI subgroup, those with ISUP GG 3-5 exhibited greater FAP expression and radiotracer uptake compared to ISUP GG 2 cases. In the two high-grade patients, [⁶⁸Ga]Ga-FAPI-46 demonstrated greater tumor uptake than [¹⁸F]PSMA / [⁶⁸Ga]Ga-PSMA PET/CT. Notably, MRI demonstrated higher diagnostic accuracy and superior local staging compared to all radiotracers evaluated.

FAP expression was detected in a subset of high-risk PC patients, particularly in those with higher-grade disease. This proof-of-concept study may suggest a role for [⁶⁸Ga]Ga-FAPI-46 PET/CT in primary PC with low PSMA avidity, but further research is warranted to define its clinical application.

Fibroblast activation protein (FAP) has emerged as one of the most promising theranostic targets. FT-FAPI, a potential FAP-targeted probe with enhanced tumor-targeting ability using an organotrifluoroborate linker, was verified for the biological effect in cell and animal experiments in previous work. However, the differences in pharmacokinetic profiles, biodistribution and dosimetry of FT-FAPI under multiple nuclides labeling in animals and humans is unclear. In this study, we sought to explore the discrepancies in the performance of FT-FAPI after labeling with different radioisotopes and to compare 68Ga-FT-FAPI with 68Ga-FAPI-04 in healthy volunteers.

Preparation and quality control of 18F-/68Ga-/177Lu-FT-FAPI injections were conducted. Biodistribution studies were performed in mice and pharmacokinetic analysis were performed using blood samples. 18F-FT-FAPI and 68Ga-FT-FAPI were initially tested in normal volunteers, respectively. Further, 68Ga-FT-FAPI was scanned at multiple time points for 1 h dynamic, 2 h and 3 h static imaging, and compared with 68Ga-FAPI-04 to clarify the distribution patterns and excretion parameters. Radiation dosimetry was estimated based on the uptake of the probes in organs of mice or humans, respectively.

18F-/68Ga-/177Lu-FT-FAPI showed high safety and tolerability in mice or humans. The pharmacokinetic characteristics of FT-FAPI in mice and humans best fit a two-compartment model. In mice, the results of biodistribution showed that the clearance half-life (T1/2β) of FT-FAPI varied with different labeled radionuclides, with 68Ga-FT-FAPI having the shortest T1/2β of 26.1 min. In HT-1080-FAP tumor-bearing mice, 177Lu-FT-FAPI showed higher tumor uptake and longer retention time than 177Lu-FAPI-04, which implies a higher radiation dose in the tumor. In healthy volunteers, both 18F-FAPI-04 and 68Ga-FT-FAPI were metabolized by the kidneys and excreted through the urinary system. The uptake of 68Ga-FT-FAPI in most normal tissues was similar to that of 68Ga-FAPI-04, being higher only in the sublingual gland, thyroid gland and pancreas. 68Ga-FT-FAPI had similar T1/2β (75.0 min vs. 77.2 min) and a slightly higher effective dose (ED) (12.4 ± 1.51 µSv·MBq-1 vs. 9.99 ± 1.85 µSv·MBq-1) compared to 68Ga-FAPI-04. Compared to 68Ga-FT-FAPI, 18F-FT-FAPI has slightly higher liver and bone uptake, especially in the delayed time points.

The pharmacokinetics of FT-FPAI varies depending on the labeled nuclide. Compared to 177Lu-FAPI-04, 177Lu-FT-FAPI showed higher tumor uptake and longer retention time. In healthy volunteers, 68Ga-FT-FAPI had lower renal uptake and higher sublingual gland, thyroid gland and pancreas uptake at 1 h p.i. than that of 68Ga-FAPI-04, with no significant differences in other organs. Further optimization will be conducted for the radiolabeling process of 18F-FT-FAPI to evaluate its diagnostic efficacy.

FAPI-PET/CT has become a promising tool for cancer diagnosis. However, the pharmacokinetic properties of FAPI tracers need optimization. Here, we developed a novel FAPI tracer, [18F]AlF-NOTA-SP2A-FAPT, for cancer imaging. NOTA-SP2A-FAPT was successfully synthesized and radiolabeled with a high radiochemical purity. [18F]AlF-NOTA-SP2A-FAPT displayed satisfying stability, hydrophilicity, and affinity to FAP, as well as specific uptake in A549-FAP cells. Micro-PET/CT showed that [18F]AlF-NOTA-SP2A-FAPT is rapidly excreted through the renal system. [18F]AlF-NOTA-SP2A-FAPT exhibited high tumor uptake and excellent retention, showing better tumor delineation compared to [18F]FDG and [18F]AlF-NOTA-FAPI-42. Pilot clinical studies of [18F]AlF-NOTA-SP2A-FAPT and head-to-head comparison with [18F]FDG were performed on 13 cancer patients. Compared to [18F]FDG, [18F]AlF-NOTA-SP2A-FAPT had higher uptake in primary tumor and lymph node metastases as well as favorable distribution and good tumor retention. In conclusion, [18F]AlF-NOTA-SP2A-FAPT demonstrated high tumor accumulation, as well as improved pharmacokinetic properties. [18F]AlF-NOTA-SP2A-FAPT could emerge as a promising alternative to the currently established FAPI tracers.

Central nervous system (CNS) tumors are quite rare but cause significant morbidity and mortality. Positron Emission Tomography (PET) is a widely utilized imaging modality within the field of nuclear medicine. CNS tumor diagnostics are an essential tool in the diagnosis and treatment of patients with glioma, offering valuable insights into tumor characteristics, treatment response and outcomes. A variety of different tracers are used in PET imaging of brain tumors including 18F-labeled fluorodeoxyglucose ([18F]FDG), markers showing amino acid metabolism, angiogenesis or inflammatory processes. In this article we describe possibility of use different tracers in different clinical scenario of CNS tumors.

Kimura's disease is a rare, chronic inflammatory disorder characterized by subcutaneous nodules, eosinophilia, and elevated serum IgE levels. It commonly affects young Asian males and typically presents in the head and neck region. Diagnosis is confirmed via histopathological examination, while treatment options include corticosteroids, surgery, and radiotherapy. [18F]AlF-NOTA-FAPI-04 PET/CT demonstrated superior imaging, with clearer background and higher target-to-background ratio, highlighting lesions with higher SUV values and greater specificity for fibroblast activity. Compared to 18F-FDG PET/CT, which is limited by nonspecific uptake in inflammatory tissues, [18F]AlF-NOTA-FAPI-04 PET/CT offers superior sensitivity and specificity in visualizing fibroblast activation. These advantages not only improve diagnostic accuracy in Kimura's disease but may also have broader implications for other eosinophilic or inflammatory disorders sharing similar clinical features. This technique improves diagnostic accuracy, facilitates treatment planning, and may guide the development of future treatment.

Fibroblast activation protein (FAP) is a type II transmembrane serine protease that is highly expressed in cancer-associated fibroblasts (CAFs) but absent in quiescent fibroblasts. Its overexpression is associated with poor prognosis in various cancers and contributes to treatment resistance. In recent years, radiolabeled FAP inhibitors (FAPI) for PET imaging have shown promising clinical value across a range of cancers. Gastrointestinal (GI) malignancies, which often exhibit a desmoplastic reaction with a high density of FAP-expressing CAFs, are particularly well-suited for FAPI PET. Given the limitations of [18F]FDG PET in GI cancers, such as low sensitivity in certain histological subtypes and high physiological background uptake, FAPI PET is expected to serve as a complementary method, potentially enhancing both diagnostic accuracy and treatment guidance. This review provides a comprehensive comparison of the clinical applications of FAPI PET and [18F]FDG PET in various GI cancers, including their value in diagnosis, staging, and treatment guidance. Additionally, this review summarizes studies on the expanding role of FAPI PET, including its use in assessing treatment response and predicting prognosis, aiming to provide insights into its potential contribution to the improved management of GI malignancies.

A 77-year-old woman who had colon cancer surgery 2 years ago underwent 68Ga-DOTA-FAPI-04 PET/CT imaging. The scan revealed nodules in liver segment II and pancreas tail, both demonstrating intense FAPI uptake. Postoperative pathology confirmed that the liver tumor was consistent with metastatic colorectal cancer, whereas the pancreatic tail nodule consisted of interlobular fibrous tissue hyperplasia with collagenous degeneration.

Nuclear medicine has evolved from a diagnostic-oriented speciality toward theranostics. Radionuclide therapy has become a booming business with newer radiopharmaceuticals and indications. Although the specialty of nuclear medicine seems scintillating, several challenges might limit sustained and long-term success. Some of the challenges and issues requiring clarification include radiopharmaceutical cost and supply, cost-benefit analysis, reimbursement, training, workforce, collaboration with the radiopharmaceutical industry, national and international nuclear medicine, and applied specialities. This review discusses these challenges and possible solutions to avoid speed breakers in theranostics.

The purpose of the current study was to compare the diagnostic performances of radiolabeled FAPI and 18F-FDG PET/CT for the detection of lymph node (LN) metastasis in head and neck cancer (HNC) patients.

The PubMed, Cochrane database, and EMBASE database, from the earliest available date of indexing through December 31, 2024, were searched for studies comparing diagnostic performances of radiolabeled FAPI and 18F-FDG PET/CT for the detection of metastatic LN in HNC patients. We estimated pooled sensitivities and specificities across studies.

Across 8 studies (14 results), the pooled sensitivity of FAPI PET/CT was 0.89 and the pooled specificity was 0.93. The pooled sensitivity of 18F-FDG PET/CT was 0.91 and the pooled specificity was 0.50. On patient-based analysis, the estimated sensitivity and specificity of FAPI were 0.96 and 0.96, and those of 18F-FDG were 0.95 and 0.34, respectively. On lesion-based analysis, the estimated sensitivity and specificity of FAPI were 0.84 and 0.94, and those of 18F-FDG were 0.86 and 0.78, respectively. On neck side-based analysis, the estimated sensitivity and specificity of FAPI were 0.88 and 0.79, and those of 18F-FDG were 0.91 and 0.29, respectively.

Radiolabeled FAPI showed a good diagnostic performance for the detection of metastatic LN in HNC patients. Also, 18F-FDG PET/CT revealed low specificity for LN staging in HNC patients. Future large multicenter research with more patients would be necessary to provide a more comprehensive overview of the usefulness of radiolabeled FAPI for LN staging in HNC patients.

This prospective study examined whether 18F-AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 (denoted as 18F-FAPI-04) positron emission tomography/computed tomography (PET/CT) can detect the development and severity of radiation esophagitis (RE) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) treated with concurrent chemoradiotherapy.

From June 2021 to March 2022, images were collected from LA-ESCC patients who underwent 18F-FAPI-04 PET/CT examinations before and during radiotherapy. The development of RE was evaluated weekly according to Radiation Therapy Oncology Group criterion. The target-to-background ratio in blood (TBRblood) was analyzed at each time point and correlated with the onset and severity of RE. Factors that predicted RE were identified by multivariate logistic analyses.

Thirty patients were evaluated. Significantly higher TBRblood (during radiotherapy, P = 0.003) and change in TBRblood compared with pre-RT (ΔTBRblood, P = 0.002) were observed in patients with RE than patients without RE. Those with grade 3 RE had a significantly higher TBRblood (during radiotherapy, P = 0.003) and ΔTBRblood (P = 0.003) compared with those with RE < grade 3. On multivariate analysis, ΔTBRblood was identified as a significant detection of any grade RE (P = 0.021) and grade 3 RE (P = 0.038).

The ΔTBRblood on 18F-FAPI-04 PET/CT may be effective at identifying patients with RE, especially grade 3 RE.

Advancements in novel peptides significantly affect cancer diagnosis by targeting cancer-specific markers, thereby improving imaging modalities, such as positron emission tomography combined with computed tomography (PET/CT) for more accurate tumor detection. This systematic review and meta-analysis aimed to assess the diagnostic accuracy of [18F] Fluorodeoxyglucose (FDG) and 68Ga-fibroblast activation protein inhibitor (FAPI- 46) PET/CT for early cancer detection.

A comprehensive search was conducted in Scopus, MEDLINE, Web of Science, and Embase databases up to March 28, 2024, using MeSH keywords. Titles and abstracts were screened to identify studies on hybrid [68Ga] FAPI- 46 and [18F] FDG, followed by a detailed full-text evaluation. Only cohort or cross-sectional studies published in English, focusing on the clinical diagnosis of cancer patients, were included, while reviews, case reports, conference proceedings, and abstracts were excluded. Random-effects meta-analysis was used for the estimation of pooled specificity and sensitivity with 95% confidence intervals (CIs). In addition, the heterogeneity was assessed across studies and subgroup meta-analyses for the detection rate via Stata.

Among the 615 retrieved studies, nine articles were incorporated in the present systematic review, with five (n = 144 patients) eligible for meta-analysis. For [68Ga] FAPI- 46, the pooled sensitivity and specificity compared with immunohistopathology were 0.96 (95% CI 0.84, 0.99) and 0.92 (95% CI 0.53, 0.99), respectively, with a positive likelihood ratio (LR +) of 4.41 (95% CI 1.64, 11.79) and a negative likelihood ratio (LR -) of 3.07 (95% CI 1.01, 9.37). For [18F] FDG, pooled sensitivity and specificity compared with immunohistopathology were 0.73 (95% CI 0.34, 0.93) and 0.83 (95% CI 0.57, 0.95), with an LR + of 12.73 (95% CI 1.43, 113.45) and an LR - of 0.32 (95% CI 0.11, 0.17). The pooled odds ratio for the detection rate on a per-lesion basis was 1.73 (95% CI 0.99, 3.02) for [68Ga] FAPI- 46 compared with [18F] FDG. The pooled weighted mean differences in the standardized uptake value (SUVmax) for primary tumor uptake and the tumor-to-background ratio (TBR) in [68Ga] FAPI- 46 vs. 18F-FDG were 4.40 (95% CI - 0.7, 9.5) and 6.18 (95% CI 1.74, 10.61), respectively. Moderate to high heterogeneity was noted because of the variations in patient selection, interpretation criteria, and scanning procedures.

This study revealed that [68Ga] FAPI- 46 outperforms [18F] FDG in cancer diagnosis, with higher sensitivity (0.96 vs. 0.73) and specificity (0.92 vs. 0.83). [Ga] FAPI- 46 improved tumor detection with higher SUVmax and TBR. While FDG had a higher LR +, its lower LR - highlighted more false negatives. Accordingly, [68Ga] FAPI- 46 exhibited superior accuracy and reliability than FDG in cancer diagnosis.

PROSPERO CRD 42023472270.

Sensitive detection of small metastatic lesions, which is highly dependent on lesion visualization, is crucial for staging lung cancer. We investigated the potential benefit of HYPER Iterative for improving the visualization of small metastatic lesions of lung cancer on early 18F-labeled fibroblast activation protein inhibitor (FAPI) PET/CT. Methods: A total of 19 patients with lung cancer underwent a 60-min [18F]F-FAPI-42 dynamic total-body uEXPLORER PET/CT scan. PET images with a 5-min acquisition time were extracted at 10, 30 min, and 60 min after tracer injection. Ordered-subset expectation maximization (OSEM) and HYPER Iterative were used for image reconstruction. SUVmax, tumor-to-liver ratio, tumor-to-blood ratio, and tumor-to-adjacent-nontumor ratio were calculated and compared between the 2 reconstruction methods and at 10, 30, and 60 min after injection. Results: All HYPER and OSEM PET images were of high quality, with HYPER PET images showing superior clarity. Small positive lesions (maximum diameter, ≤1 cm) were depicted clearer on HYPER PET than on OSEM PET images at all time points, particularly at 10 min after injection, where 16.4% of lesions were poorly visualized on OSEM PET but clearly depicted on HYPER PET images. The tumor-to-liver ratio, tumor-to-blood ratio, and tumor-to-nontumor ratio at 10, 30, and 60 min after injection scan on HYPER PET images were significantly higher than those on OSEM images at corresponding time points (P ≥ 0.05 for all comparisons). SUVmax was more than 2-fold greater in large positive lesions (maximum diameter, >1.0 cm) than in small positive lesions (maximum diameter, ≤1 cm) on both OSEM and HYPER PET images at 10, 30, and 60 min after injection (P < 0.05 for all comparisons). The visualization of large positive lesions was not significantly affected by reconstruction methods or scan times. Conclusion: HYPER Iterative reconstruction enhanced the visualization of small metastatic lesions in lung cancer when compared with conventional OSEM, enabling effective early imaging using [18F]F-FAPI-42 uEXPLORER total-body PET/CT at 10 min after tracer injection.

Rejection, especially chronic rejection is a key factor influencing the prognosis of kidney transplantation patients. While 18F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT has been widely utilized for diagnosing various diseases, its diagnostic efficacy in kidney transplant rejection remains unexplored.

In this study, 24 kidney transplant recipients were prospectively enrolled and divided into a control cohort and a rejection cohort (KTR), which were further classified into acute rejection (AR), mixed rejection (MR), and chronic rejection (CR) subgroups. All patients underwent 18F-FAPI-04 PET/CT and 18F-FDG PET/CT scans, along with immunohistochemical FAP staining and Banff pathological scoring. The maximum and average standardized uptake values (SUVs) of the two imaging methods were calculated.

Compared with the control cohort, the KTR cohort showed significantly higher serum creatinine levels, lower estimated glomerular filtration rates, and lower hemoglobin levels. The SUVmax of 18F-FAPI-04 PET/CT in the allograft kidney cortex (AKC) and allograft kidney biopsy site (AKB) in the KTR cohort was significantly greater than that in the control cohort. The SUVmax of 18F-FDG PET/CT between the two cohorts was significantly different only in the AKC. For the KTR cohort, the SUVmax of 18F-FAPI-04 PET/CT in AKC and AKB was considerably greater than that of 18F-FDG PET/CT (5.5 vs. 2.8 and 3.6 vs. 2.5, respectively; both p < 0.01). In the CR cohort, the SUVmax of 18F-FAPI-04 PET/CT in the AKC, AKB, and allograft kidney medulla (AKM) was significantly greater (7.1, 5.3, and 3.2) than that of 18F-FDG PET/CT (2.5, 2.1 and 1.8) (p = 0.009, 0.009 and 0.016, respectively). The SUVmax of 18F-FAPI-04 PET/CT in AKB increased gradually in the AR, MR, and CR cohorts (2.8 vs. 3.6 vs. 5.3, p = 0.02). The above results were consistent with the SUVavg statistics. The number of FAP-positive stromal cells was different between the control and KTR groups and among the AR, MR, and CR subgroups.

18F-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in distinguishing kidney transplant rejection, especially chronic rejection.

Theranostics represents the state-of-the-art in precision oncology treatment, and is gaining momentum because of the potential to help improve outcomes for even late-stage cancer patients. Pairs of identical (or very similar) molecules are labeled with both diagnostic and therapeutic radionuclides, and used to both image and treat cancer. The FDA approval and commercialization of theranostics for neuroendocrine tumors and prostate cancer has spurred development of new theranostics as well as significant venture and pharma investment, such that both academic medical centers and companies are working to advance the field. One theranostic target of interest is the Fibroblast Activation Protein (FAP) because its expression in many different tumor types offers potential for a pan-cancer theranostic. In this Patent Spotlight, we present the first analysis of patents issued for FAP-targeting radiopharmaceuticals, providing perspective on current trends and challenges as well as future directions.

This prospective study aims to assess the feasibility of a one-stop imaging protocol using 68 Ga-FAPI-04/ 18 F-FDG dual-radiotracer with dual-low-activity for tumor imaging.

Forty patients underwent one-stop 68 Ga-FAPI-04 PET (PET FAPI ) and dual-radiotracer PET (PET DUAL ) using a total-body PET/CT scanner with a 194-cm axial field of view. After a half-dose (0.925 MBq/kg) 68 Ga-FAPI-04 PET/CT, an additional half-dose (1.85 MBq/kg) of 18 F-FDG was administered for a 60-minute dynamic acquisition. PET DUAL was reconstructed at 10-minute intervals (PET D0-10 , PET D10-20 , PET D20-30 , PET D30-40 , PET D40-50 , and PET D50-60 ). Data of lesion detectability, target-to-background ratios, tumor staging, and total radiation dose were analyzed. A target-to-liver ratio (TLR) ≥ 3 on PET FAPI was considered indicative of sufficient fibroblast activation protein expression.

PET D50-60 and PET FAPI showed similar performance in detecting primary tumors (42 vs 41, P  > 0.999). However, significantly more metastatic lesions were identified on PET D50-60 compared with PET FAPI (102 vs 60, P  < 0.001). PET FAPI demonstrated significantly higher TLR, target-to-blood-pool ratio, and target-to-normal-tissue ratio than PET DUAL ( P  < 0.05). Lesion detectability was similar across PET D10-20 , PET D20-30 , PET D30-40 , PET D40-50 , and PET D50-60 (all P 's > 0.05). Notably, PET D30-40 and PET D40-50 detected all lesions identified by PET D50-60 . PET D40-50 showed no significant differences in TLR, target-to-blood-pool ratio, and target-to-normal-tissue ratio compared with PET D50-60 ( P  > 0.05). Up to 94.9% of malignant primary lesions exhibited a TLR ≥ 3 on PET FAPI . The average effective dose was 9.85 ± 2.19 mSv, similar to that of a whole-body 18 F-FDG PET/CT.

This one-stop, dual-radiotracer, dual-low-activity imaging protocol combines the strengths of 68 Ga-FAPI-04 and 18 F-FDG, offering a shorter imaging duration and reduced radiation exposure.

Fibrosis is one of the key healing responses to injury, especially within the heart, where it helps to maintain structural integrity following acute insults such as myocardial infarction. However, if it becomes dysregulated, then fibrosis can become maladaptive, leading to adverse remodelling, impaired cardiac function and heart failure. Fibroblast activation protein is exclusively expressed by activated fibroblasts, the key effector cells of fibrogenesis, and has a unique extracellular domain that is an ideal ligand for novel molecular imaging probes. Fibroblast activation protein inhibitor (FAPI) radiotracers have been developed for positron emission tomography (PET) imaging, demonstrating high selectivity for activated fibroblasts across a range of different pathologies and disparate organ systems. In this review, we will summarise the role of fibroblast activation protein in cardiovascular disease and how FAPI radiotracers might improve the assessment and treatment of patients with cardiovascular diseases.

[18F]FDG PET/CT is the most widely used PET radiopharmaceutical in oncology, but it is not exempt of diagnostic limitations. FAPI have emerged as a great tool in the management of several different solid tumours in which [18F]FDG is not able to provide enough information. The aim of this work was to evaluate the available evidence on diagnostic and therapeutic applications of PET/CT with FAPI radiopharmaceuticals. We underwent a non-systematic review focusing in the utility of FAPI radiopharmaceuticals in PET/CT diagnosis and in the treatment of several malignancies. FAPI radiopharmaceuticals present characteristics that can potentially overcome some known diagnostic limitations of [18F]FDG. FAPI radiopharmaceuticals present a high target-to-background ratio (TBR) in many solid tumours such as oesophageal cancer, gastric cancer, pancreatic cancer, hepatic cancer, colorectal cancer, breast cancer, ovarian, cervical cancer, and head and neck cancer. Available evidence suggests the high TBR improves sensitivity and specificity compared to [18F]FDG, especially for the detection of lymphadenopathies and peritoneal metastases, and may improve patient management and radiation treatment planning. Moreover, it is important to underline the potential theranostic application of FAPI radiopharmaceuticals.

This study aimed to compare the diagnostic efficacy of [ 68 Ga]Ga-DOTA.SA.FAPi and [ 18 F]F-FDG PET/CT for detecting primary and metastatic lesions in sarcoma patients.

The analysis included both patient-based and lesion-based comparisons of PET/CT scans in individuals with histologically confirmed sarcoma.

A total of 23 sarcoma patients (mean age 43.0 ± 16.5 years; range: 21-76 years) underwent both [ 18 F]F-FDG and [ 68 Ga]Ga-DOTA.SA.FAPi PET/CT scans. Histological distribution included 30% synovial sarcoma, 13% liposarcoma, and 21.7% leiomyosarcoma, with 70% of patients presenting with distant metastases. Detection rates for primary tumors were similar between [ 68 Ga]Ga-DOTA.SA.FAPi and [ 18 F]F-FDG PET/CT (85.7% vs 100%, P  = 0.149). Lymph node detection rates were also comparable (80% vs 100%, P  = 0.146). Lesion-based analysis revealed that [ 68 Ga]Ga-DOTA.SA.FAPi detected 220 lesions (83% efficiency) compared with 249 lesions (94% efficiency) for [ 18 F]F-FDG ( P  < 0.0001). Notably, [ 68 Ga]Ga-DOTA.SA.FAPi demonstrated superior detection of liver (54 vs 38 lesions, P  < 0.0001) and bone metastases (125 vs 102 lesions, P  < 0.0001).

Our study shows that although [ 18 F]F-FDG PET/CT offers superior overall lesion detection efficiency, [ 68 Ga]Ga-DOTA.SA.FAPi PET/CT excels in identifying specific metastatic sites, particularly in bone and liver. These findings highlight the complementary roles of both imaging modalities in sarcoma evaluation.

Since fibroblast activation protein (FAP), one predominant biomarker of cancer associated fibroblasts (CAFs), is highly expressed in the tumor stroma of various epidermal-derived cancers, targeting FAP for tumor diagnosis and treatment has shown substantial potentials in both preclinical and clinical studies. However, in preclinical settings, tumor-bearing mice exhibit relatively low absolute FAP expression levels, leading to challenges in acquiring high-quality PET images using radiolabeled FAP ligands (FAPIs) with low molar activity, because of which a saturation effect in imaging is prone to happen. Moreover, how exactly the molar dose of FAPI administered to a mouse influences the targeted PET imaging and radiotherapy remains unclear now. Therefore, this study aims to investigate the impacts of the molar dose of the administered FAPI on FAP-targeted PET imaging and radiotherapy in mouse syngeneic tumor models.

[68Ga]Ga-FAPI-04 with various molar doses of FAPI-04 was administered to wild-type 4T1 tumor-bearing mice, followed by static PET imaging. Sigmoidal curves were generated to analyze the correlation between the standard uptake value (SUV) and the administered molar doses of FAPI-04. Similarly, [177Lu]Lu-DOTAGA.(SA.FAPi)2 with a consistent dose of radioactivity but containing different moles of DOTAGA.(SA.FAPi)2 were injected into 4T1 tumor-bearing mice to assess the therapeutic effect. [68Ga]Ga-FAPI-04 was also applied to different tumor models for PET/CT imaging.

A gradient blocking effect was observed with increasing FAPI molar dose in [68Ga]Ga-FAPI-04 PET imaging and [177Lu]Lu-DOTAGA.(SA.FAPi)2 treatment, with various imaging and therapeutic outcomes. [68Ga]Ga-FAPI-04 PET exhibit potentials to characterize murine derived FAP expression with low molar dose of administered FAPI-04 using various tumor models.

The molar dose of FAPI in [68Ga]Ga/[177Lu]Lu-FAPI had a substantial impact on FAP-targeted imaging and therapy in mouse syngeneic tumor models. To acquire enhanced reliability and reproducibility in preclinical situation, it is critical to carefully consider the molar dose of the radiotracer when applying radiolabeled FAP ligands to FAP-targeted imaging and radiotherapy.

PET/CT targeting fibroblast activation protein α (FAP) in cancer-associated fibroblasts shows promise in theranostics. Here, we report the case of a 31-year-old woman with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer who presented with rising CA15-3 for further diagnostic workup. Whereas [ 18 F]FDG PET/CT was unremarkable, novel [ 68 Ga]RTX-1363 PET/CT revealed intense tracer accumulation in thoracoabdominal lymph nodes and both ovaries. Follow-up imaging confirmed tumor progression, and diagnostic laparoscopy verified metastatic disease in the ovaries with high FAP expression in the tumor stroma. This case underscores the superior sensitivity of [ 68 Ga]RTX-1363 PET/CT over [ 18 F]FDG PET/CT, enhancing breast cancer diagnostic and therapeutic strategies.

Background/Objectives: Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [68Ga]Ga-DATA5m.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. Methods: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [68Ga]Ga-DATA5m.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. Results: Cardiac uptake of [68Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, n = 7 vs. SHAM: 1.1 ± 0.2%ID/g, n = 5; p = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, n = 4 vs. SHAM: 0.8 ± 0.0%ID/g, n = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, n = 6; p = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. Conclusions: This study demonstrated the efficacy of [68Ga]Ga-DATA5m.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients.

Molecular imaging-guided techniques increase precision in surgical procedure and reduce postinterventional morbidity. Fibroblast activation protein (FAP) ligands may contribute to the superior preoperative assessment compared with conventional radionuclides due to its higher sensitivity and tumor delineation in epithelial malignancies. Wide spectrum of currently available FAP ligands including diagnostic and therapeutic emitters allows a flexibility regarding the optimal choice for individual need. Moreover, newly introduced hybrid tracers with fluorescence-based FAP probes enrich this spectrum by providing intraoperative FAP-targeting without radiation exposure. Thus, the use of FAP ligands in interventional oncology has great promise in improving the efficiency of local-interventional surgery.

Metastatic prostate cancer (mPCa) remains a significant cause of cancer-related mortality in men. Advances in molecular profiling have demonstrated that the androgen receptor (AR) axis, DNA damage repair pathways, and the PI3K/AKT/mTOR pathway are critical drivers of disease progression and therapeutic resistance. Despite the established benefits of hormone therapy, chemotherapy, and bone-targeting agents, mPCa commonly becomes treatment-resistant. Recent breakthroughs have highlighted the importance of identifying actionable genetic alterations, such as BRCA2 or ATM defects, that render tumors sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Parallel efforts have refined imaging-particularly prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography-to detect and localize metastatic lesions with high sensitivity, thereby guiding patient selection for PSMA-targeted radioligand therapies. Multi-omics innovations, including liquid biopsy technologies, enable the real-time tracking of emergent AR splice variants or reversion mutations, supporting adaptive therapy paradigms. Nonetheless, the complexity of mPCa necessitates combination strategies, such as pairing AR inhibition with PI3K/AKT blockade or PARP inhibitors, to inhibit tumor plasticity. Immuno-oncological approaches remain challenging for unselected patients; however, subsets with mismatch repair deficiency or neuroendocrine phenotypes may benefit from immune checkpoint blockade or targeted epigenetic interventions. We present these pivotal advances, and discuss how biomarker-guided integrative treatments can improve mPCa management.

Locoregional therapies (LRTs) play a considerable role in the management of hepatocellular carcinoma (HCC), especially for patients who are not suitable for radical resection or transplantation. In clinical practice, assessment of LRTs is mainly based on computed tomography and MR imaging, but functional and metabolic information is less accessible. This article reviews the use of various the standardized uptake value parameters based on PET and multiple radiotracers for managing HCC after treatment with different LRTs, as well as parts of preclinical research. It discusses the current use of PET in more detail, as well as its advantages, disadvantages, and prospects.

This study aims to systematically review and perform a meta-analysis to compare the diagnostic performance of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in gynaecological cancers.

A comprehensive search of PubMed/MEDLINE and EMBASE was conducted and updated to October 25, 2024, to identify clinical studies evaluating FAPI and [18F]FDG PET/CT or PET/MR in patients with gynaecological cancer. Quality was assessed using the QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies). Per-lesion pooled estimates of sensitivity, specificity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals.

Ten studies were included for qualitative assessment and five studies focusing on ovarian cancer were included in the meta-analysis. The detection rates of primary cervical cancer ranged from 96 to 100% for both radiopharmaceuticals. For the primary tumour in ovarian cancer, the pooled sensitivities of 68Ga-FAPI and [18F]FDG were 95% and 92%, and the pooled specificities were 81% for both radiopharmaceuticals. Nodal metastases detection was higher with 68Ga-FAPI compared with [18F]FDG in cervical cancer. Similarly, in ovarian cancer the estimated pooled sensitivities of 68Ga-FAPI and [18F]FDG were 97% and 88%, and the pooled specificities were 83% and 41%, respectively. At peritoneal metastases analysis in ovarian cancer, the pooled sensitivities of 68Ga-FAPI and [18F]FDG were 97% and 70%, and the pooled specificities were 93% and 88%, respectively. At the visual assessment of peritoneal cancer scores, such as peritoneal cancer index, 68Ga-FAPI detected a greater tumour burden compared with [18F]FDG. A comparative analysis of the PET semiquantitative parameters was also performed.

Despite limited literature data, radiopharmaceuticals based on FAPIs are a promising alternative to [18F]FDG for imaging gynaecological cancers, in particular for the detection of nodal metastases in cervical and ovarian cancers, as well as for detecting peritoneal metastases in ovarian cancers. Larger prospective studies are needed to confirm these results and promote the inclusion of FAPI radiopharmaceuticals in clinical practice.

Not applicable.

Fibroblast activation protein (FAP) is a serine protease selectively expressed in cancer-associated fibroblasts (CAFs), fibrotic tissues, and areas of active tissue remodeling, making it an attractive target for diagnostic imaging across a spectrum of disease. FAP inhibitors (FAPIs) labeled with PET tracers have rapidly advanced as a novel imaging modality with broad clinical applications that offers several advantages, including rapid tumor accumulation, low background uptake, and high tumor-to-background ratios. In oncology, FAPI PET has demonstrated excellent performance in visualizing a wide range of malignancies, including those with low glycolytic activity, such as pancreatic cancer, cholangiocarcinoma, and certain sarcomas. Its high sensitivity and specificity for the stromal component enables improved tumor delineation, staging, and response assessment. Additionally, the potential to guide theranostic approaches, where the same tracer can be labeled with therapeutic radionuclides, positions FAPI as a key player in precision oncology. Beyond oncology, FAPI PET has shown promise in imaging conditions characterized by fibrotic and inflammatory processes. In the cardiovascular field, FAPI PET imaging is being investigated for its ability to detect myocardial fibrosis and active cardiac remodeling, crucial in conditions like heart failure, post-myocardial infarction remodeling, and hypertrophic cardiomyopathy. This review highlights the expanding clinical applications of FAPI-based PET imaging across oncology, inflammation, and cardiovascular disease. While the current data are promising, further large-scale studies and multicenter trials are essential to validate these findings and establish standardized protocols. The versatility and broad applicability of FAPI PET underscore its potential as a transformative tool in precision medicine.

This study aimed to develop a radiomics model characterized by 68Ga-fibroblast activation protein inhibitors (FAPI) positron emission tomography (PET) imaging to predict microvascular invasion (MVI) of hepatocellular carcinoma (HCC). This study also investigated the impact of varying thresholds for maximum standardized uptake value (SUVmax) in semi-automatic delineation methods on the predictions of the model.

This retrospective study included 84 HCC patients who underwent 68Ga-FAPI PET and their MVI results were confirmed by histopathological examination. Volumes of interest (VOIs) for lesions were semi-automatically delineated with four thresholds of 30%, 40%, 50%, and 60% for SUVmax. Extracted shape features, first-, second- and higher-order features. Eight PET radiomics models for predicting MVI were constructed and tested.

In the testing set, the logistic regression (LR) model achieved the highest AUC values for three groups of 30%, 50%, and 60%, with values of 0.785, 0.896, and 0.859, respectively, while the random forest (RF) model in 40% group obtained the highest AUC value of 0.815. The LR model in 50% group and the extreme gradient boosting (XGBoost) model in 60% group achieved the highest accuracy, each at 87.5%. The highest sensitivity was observed in the support vector machine (SVM) model in 30% group, at 100%.

The 68Ga-FAPI PET radiomics model has high efficacy in predicting MVI in HCC, which is important for the development of HCC treatment plan and post-treatment evaluation. Different thresholds of SUVmax in semi-automatic delineation methods exert a degree of influence on performance of the radiomics model.