Copper homeostasis imbalance and cuproptosis: Emerging targets and strategies for gastrointestinal tumor therapy

Table 3 Positron emission tomography and multimodal imaging strategies for copper-based theragnostics

Imaging strategy	Representative platform	Main therapeutic mechanism	Evidence status/limitation	Ref.
64Cu-PET + phototherapy	64Cu-labeled porphyrin-lipid nanoparticles	PET tracking of tumor uptake and photochemical ablation	Useful for biodistribution monitoring; cuproptosis relevance is indirect
64Cu-PET + chemotherapy	CCR2-targeted Cu@CuOx nanoparticles loaded with gemcitabine	PET imaging and drug delivery in PDAC	Tumor-targeted strategy; clinical validation required	[279]
64Cu-PET + chemo/radiotherapy	Albumin-binding camptothecin nanoprodrug	Tumor retention, PET imaging, chemotherapy and radiotherapy	Strong theragnostic design; mainly proof-of-concept	[280]
64Cu-PET targeted therapy	64Cu-labeled immunoliposomes	EGFR-targeted PET imaging and therapy	Applicable to receptor-high tumors; tumor selectivity is key	[281]
PET-guided BNCT	64Cu-chelated boron neutron capture therapy platform	PET tracking of boron agent accumulation	Supports treatment planning; not primarily cuproptosis-based	[282]
UCL/CT/MRI-guided therapy	Upconversion nanoplatforms encapsulating CuS	Radiotherapy and PTT	Multimodal imaging enables guidance, but platform complexity is high	[283]
Four-modal imaging	CuS and rare-earth nanoparticle-loaded zeolitic imidazolate composites	Imaging-guided chemoradiotherapy	Broad imaging capacity; translational reproducibility uncertain
MRI-guided X-ray PDT	Copper-cysteine nanoparticles	Deep-tumor PDT under X-ray irradiation	Suitable for deep lesions; mechanism is mainly ROS-based	[284]
Fluorescence/MRI-guided CDT	CuS/Gd2O3based nanoprobes	Thermally enhanced CDT	Useful dual-modal design; cuproptosis specificity remains to be proven	[285]
Multiparametric MRI response monitoring	CuS@GOD nanoparticles	Starvation therapy, ROS generation, treatment response assessment	Imaging mainly monitors response rather than directly proving cuproptosis	[286]

PET: Positron emission tomography; CCR2: C-C motif chemokine receptor 2; PDAC: Pancreatic ductal adenocarcinoma; EGFR: Epidermal growth factor receptor; BNCT: Boron neutron capture therapy; UCL: University College London; CT: Computed tomography; MRI: Magnetic resonance imaging; PTT: Photothermal therapy; PDT: Photodynamic therapy; ROS: Reactive oxygen species; CDT: Chemodynamic therapy.