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Tamizh Selvan G, Venkatachalam P. Potentials of cytokinesis blocked micronucleus assay in radiation triage and biological dosimetry. J Genet Eng Biotechnol 2024; 22:100409. [PMID: 39674629 PMCID: PMC11381789 DOI: 10.1016/j.jgeb.2024.100409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/04/2024] [Accepted: 08/06/2024] [Indexed: 09/11/2024]
Abstract
The measurement of micronucleus (MN) in the cytokinesis-block arrested binucleated cells has been extensively used as a biomarker in many radiation biology applications in specific biodosimetry. Following radiation casualties, medical management of exposed individuals begins with triage and biological dosimetry. The cytokinesis blocked micronucleus (CBMN) assay is the alternate for the gold standard dicentric chromosome assay in radiation dose assessment. In recent years, the CBMN assay has become well-validated and emerged as a method of choice for evaluating occupational and accidental exposures scenario. It is feasible due to its cost-effective, simple, and rapid dose assessment rather than a conventional chromosome aberration assay. PubMed search tool was used with keywords of MN, biodosimetry, radiotherapy and restricted to human samples. Since Fenech and Morely developed the assay, it has undergone many technical and technological reforms as a biomarker of various applications. In this review, we have abridged recent developments of the CBMN assay in radiation triage and biodosimetry, focusing on (a) the influence of variables on dose estimation, (b) the importance of baseline frequency and reported dose-response coefficient values among different laboratories, (c) inter-laboratory comparison and (d) its limitations and means to overcome them.
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Affiliation(s)
- G Tamizh Selvan
- Central Research Laboratory, K.S. Hegde Medical Academy, NITTE (Deemed to be University), Deralakatte, Mangalore, Karnataka, India.
| | - P Venkatachalam
- Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India
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Vinnikov V, Belyakov O. Clinical Applications of Biological Dosimetry in Patients Exposed to Low Dose Radiation Due to Radiological, Imaging or Nuclear Medicine Procedures. Semin Nucl Med 2021; 52:114-139. [PMID: 34879905 DOI: 10.1053/j.semnuclmed.2021.11.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Radiation dosimetric biomarkers have found applications beyond radiation protection area and now are actively introduced into clinical practice. Cytogenetic assays appeared to be a valuable tool for individualized quantifying radiation effects in patients, with high capability for assessing genotoxicity of various medical exposure modalities and providing meaningful radiation dose estimates for prognoses of radiation-related cancer risk. This review summarized current data on the use of biological dosimetry methods in patients undergoing various medical irradiations to low doses. The highlighted topics include basic aspects of biological dosimetry and its limitations in the range of low radiation doses, and main patterns of in vivo induction of radiation biomarkers in clinical exposure scenarios, occurring in X-ray diagnostics, computed tomography, interventional radiology, low dose radiotherapy, and nuclear medicine (internally administered 131I and other radiopharmaceuticals). Additionally, several specific issues, examined by biodosimetry techniques, are analysed, such as contrast media effect, radiation response in pediatric patients, impact of magnetic resonance imaging, evaluation of radioprotectors, detection of patients' abnormal intrinsic radiosensitivity and dose estimation in persons involved in medical radiation incidents. A prognosis of possible directions for further improvements in this area includes the automation of cytogenetic analysis, introduction of molecular biodosimeters and development of multiparametric biodosimetry platforms. A potential approach to the advanced biodosimetry of internal exposure and/or low dose external irradiation is suggested; this can be a multiparametric platform based on the combination of the γ-H2AX foci, dicentric, and translocation assays, each applied in the optimum postexposure time range, with the amalgamation of the dose estimates. The study revealed the necessity of further research, which might clarify medical radiation safety concerns for patients via using stringent biodosimetry methodology.
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Affiliation(s)
- Volodymyr Vinnikov
- International Atomic Energy Agency (IAEA), Vienna, Austria; Grigoriev Institute for Medical Radiology and Oncology (GIMRO), Kharkiv, Ukraine.
| | - Oleg Belyakov
- International Atomic Energy Agency (IAEA), Vienna, Austria
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Giussani A, Lopez MA, Romm H, Testa A, Ainsbury EA, Degteva M, Della Monaca S, Etherington G, Fattibene P, Güclu I, Jaworska A, Lloyd DC, Malátová I, McComish S, Melo D, Osko J, Rojo A, Roch-Lefevre S, Roy L, Shishkina E, Sotnik N, Tolmachev SY, Wieser A, Woda C, Youngman M. Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2020; 59:357-387. [PMID: 32372284 PMCID: PMC7369133 DOI: 10.1007/s00411-020-00845-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 04/15/2020] [Indexed: 05/17/2023]
Abstract
This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel. Based on real-case scenarios, dose estimates obtained from bioassay data as well as with biological and/or EPR dosimetry are compared and critically discussed. In most of the scenarios presented, concomitant external exposures were responsible for the greater portion of the received dose. As no assay is available which can discriminate between radiation of different types and different LETs on the basis of the type of damage induced, it is not possible to infer from these studies specific conclusions valid for incorporated radionuclides alone. The biological dosimetry assays and EPR techniques proved to be most applicable in cases when the radionuclides are almost homogeneously distributed in the body. No compelling evidence was obtained in other cases of extremely inhomogeneous distribution. Retrospective dosimetry needs to be optimized and further developed in order to be able to deal with real exposure cases, where a mixture of both external and internal exposures will be encountered most of the times.
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Affiliation(s)
- A Giussani
- BfS-Bundesamt für Strahlenschutz, Ingolstädter Landstr. 1, 85764, Oberschleißheim, Germany.
| | - M A Lopez
- CIEMAT - Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Av.da Complutense 40, 28040, Madrid, Spain
| | - H Romm
- BfS-Bundesamt für Strahlenschutz, Ingolstädter Landstr. 1, 85764, Oberschleißheim, Germany
| | - A Testa
- ENEA Casaccia Research Center, Via Anguillarese 301, Santa Maria di Galeria, 00123, Rome, Italy
| | - E A Ainsbury
- Public Health England - Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, OX11 0RQ, Oxon, UK
| | - M Degteva
- Urals Research Center for Radiation Medicine (URCRM), Vorovskt str. 68A, Chelyabinsk, 454141, Russia
| | - S Della Monaca
- Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - G Etherington
- Public Health England - Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, OX11 0RQ, Oxon, UK
| | - P Fattibene
- Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - I Güclu
- Cekmece Nuclear Research and Training Center Radiobiology Unit Yarımburgaz, Turkish Atomic Energy Authority, Istanbul, Turkey
| | - A Jaworska
- DSA-Norwegian Radiation and Nuclear Safety Authority, Skøyen, P. O. Box 329, 0213, Oslo, Norway
| | - D C Lloyd
- Public Health England - Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, OX11 0RQ, Oxon, UK
| | - I Malátová
- SURO-National Radiation Protection Institute, Bartoskova 28, 14000, Prague, Czech Republic
| | - S McComish
- US Transuranium and Uranium Registries, Washington State University, Richland, WA, USA
| | - D Melo
- Melohill Technology, 1 Research Court, Rockville, MD, 20850, USA
| | - J Osko
- National Centre for Nuclear Research, A. Soltana 7, 05400, Otwock, Poland
| | - A Rojo
- ARN-Nuclear Regulatory Authority of Argentina, Av. del Libertador 8250, Buenos Aires, Argentina
| | - S Roch-Lefevre
- Institut de Radioprotection et de Sûreté Nucléaire, IRSN, Pôle Santé et Environnement, Direction de la Santé, Fontenay-aux-Roses, France
| | - L Roy
- Institut de Radioprotection et de Sûreté Nucléaire, IRSN, Pôle Santé et Environnement, Direction de la Santé, Fontenay-aux-Roses, France
| | - E Shishkina
- Urals Research Center for Radiation Medicine (URCRM), Vorovskt str. 68A, Chelyabinsk, 454141, Russia
- Chelyabinsk State University (ChelSU), 129, Bratiev Kashirinih Street, Chelyabinsk, 454001, Russia
| | - N Sotnik
- Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region, 456780, Russia
| | - S Y Tolmachev
- US Transuranium and Uranium Registries, Washington State University, Richland, WA, USA
| | - A Wieser
- Institute of Radiation Medicine, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
| | - C Woda
- Institute of Radiation Medicine, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
| | - M Youngman
- Public Health England - Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, OX11 0RQ, Oxon, UK
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Meenakshi C, Venkatraman B. Correlation between cytogenetic biomarkers obtained from DC and CBMN assays caused by low dose radon exposure in smokers. Int J Radiat Biol 2019; 95:1268-1275. [DOI: 10.1080/09553002.2019.1625494] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- C. Meenakshi
- Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, India
| | - B. Venkatraman
- Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, India
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Perumal V, Sekaran TSG, Raavi V, Basheerudeen SAS, Kanagaraj K, Chowdhury AR, Paul SFD. Radiation signature on exposed cells: Relevance in dose estimation. World J Radiol 2015; 7:266-278. [PMID: 26435777 PMCID: PMC4585950 DOI: 10.4329/wjr.v7.i9.266] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 07/03/2015] [Accepted: 08/03/2015] [Indexed: 02/06/2023] Open
Abstract
The radiation is considered as a double edged sword, as its beneficial and detrimental effects have been demonstrated. The potential benefits are being exploited to its maximum by adopting safe handling of radionuclide stipulated by the regulatory agencies. While the occupational workers are monitored by personnel monitoring devices, for general publics, it is not a regular practice. However, it can be achieved by using biomarkers with a potential for the radiation triage and medical management. An ideal biomarker to adopt in those situations should be rapid, specific, sensitive, reproducible, and able to categorize the nature of exposure and could provide a reliable dose estimation irrespective of the time of the exposures. Since cytogenetic markers shown to have many advantages relatively than other markers, the origins of various chromosomal abnormalities induced by ionizing radiations along with dose-response curves generated in the laboratory are presented. Current status of the gold standard dicentric chromosome assay, micronucleus assay, translocation measurement by fluorescence in-situ hybridization and an emerging protein marker the γ-H2AX assay are discussed with our laboratory data. With the wide choice of methods, an appropriate assay can be employed based on the net.
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Muikku M, Huikari J, Korpela H, Lindholm C, Paile W, Parviainen T. Occupational exposure to 131I-a case study. HEALTH PHYSICS 2014; 107:351-355. [PMID: 25162426 DOI: 10.1097/hp.0000000000000147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
In a laboratory in a company manufacturing radiopharmaceuticals, a laboratory technician was contaminated with I. The employee was preparing I capsules for thyroid carcinoma treatment. The employee was wearing two pairs of protective gloves and, when changing gloves, noticed a rupture in the right inner glove but no visible rupture in the outer glove. Only 3-4 h later, routine monitoring revealed heavy contamination of the back of the right hand. Immediate actions to decontaminate the hand were taken on-site. Stable iodine was not administered. On the next day, besides persisting heavy contamination of the hand, I was also detected in the thyroid gland. Based on original measurements on-site and later follow-up at STUK, including surface contamination measurements and whole body counting, the original I activity on the hand was estimated at 12 MBq and the superficial skin dose at 33 Gy, affecting a skin area of about 10 cm. The thyroid dose was estimated at 430 mGy. Eleven days after the incident, the skin was dry and slightly desquamated. After 15 d, the skin was intact with no desquamation left. No further signs of skin damage have occurred. Cytogenetic analysis of circulating lymphocytes indicated a slight elevation of chromosomal aberrations.
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Affiliation(s)
- Maarit Muikku
- *STUK-Radiation and Nuclear Safety Authority, P.O. Box 14, FIN-00881, Helsinki, Finland
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Loke KSH, Padhy AK, Ng DCE, Goh ASW, Divgi C. Dosimetric considerations in radioimmunotherapy and systemic radionuclide therapies: a review. World J Nucl Med 2012; 10:122-38. [PMID: 22144871 PMCID: PMC3227338 DOI: 10.4103/1450-1147.89780] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Radiopharmaceutical therapy, once touted as the “magic bullet” in radiation oncology, is increasingly being used in the treatment of a variety of malignancies; albeit in later disease stages. With ever-increasing public and medical awareness of radiation effects, radiation dosimetry is becoming more important. Dosimetry allows administration of the maximum tolerated radiation dose to the tumor/organ to be treated but limiting radiation to critical organs. Traditional tumor dosimetry involved acquiring pretherapy planar scans and plasma estimates with a diagnostic dose of intended radiopharmaceuticals. New advancements in single photon emission computed tomography and positron emission tomography systems allow semi-quantitative measurements of radiation dosimetry thus allowing treatments tailored to each individual patient.
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Affiliation(s)
- Kelvin S H Loke
- Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore
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Oger E, Lavenu A, Bellissant E, Garin E, Polard E. Meta-analysis of interstitial pneumonia in studies evaluating iodine-131-labeled lipiodol for hepatocellular carcinoma using exact likelihood approach. Pharmacoepidemiol Drug Saf 2011; 20:956-63. [PMID: 21748824 DOI: 10.1002/pds.2177] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2010] [Revised: 04/18/2011] [Accepted: 04/21/2011] [Indexed: 12/18/2022]
Abstract
PURPOSE Iodine-131-labeled lipiodol is currently licensed for unresectable hepatocellular carcinoma with portal thrombosis. It is thought to be well tolerated. Cases of interstitial pneumonia have been reported, but their frequency (≈2%) has not been well estimated. Quantifying adverse drug event frequency requires an appropriate statistical approach because standard methods are biased. METHODS To estimate the frequency of interstitial pneumonia in patients with hepatocellular carcinoma receiving iodine-131-labeled lipiodol, we conducted a systematic review of English articles using MEDLINE and EMBASE. All types of articles were considered except case reports. Primary outcome measure was symptomatic interstitial pneumonia based on investigators' judgment. All pooled analyses were based on a random effects meta-analysis model using an exact likelihood approach based on the binomial within-study distribution. RESULTS Ten studies, including 142 patients, used low activity per dose, ranging from 0.3 to 1.1 GBq. No respiratory adverse event was noticed in these studies. Eighteen studies, including 542 patients, evaluated higher activity per dose, around 2.2 GBq; 24 cases of interstitial pneumonia were reported in these studies. Estimated frequency of interstitial pneumonia was 1.6% (95%CI, 0.4-6.4%) after one high dose and 4.1% (95%CI, 1.0-16.0%) after two or more high doses. CONCLUSIONS The frequency of interstitial pneumonia appears higher and more precise than previously estimated. The risk appears to be related to the number of injections and the dose level per injection. Generalized linear mixed models using the exact binomial within-study distribution initially described to summarize data on diagnostic evaluation could be relevant for drug-related adverse reaction frequency assessment.
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Affiliation(s)
- Emmanuel Oger
- Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Clinical Pharmacology Department, Rennes University Hospital, Rennes, France.
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Vral A, Fenech M, Thierens H. The micronucleus assay as a biological dosimeter of in vivo ionising radiation exposure. Mutagenesis 2011; 26:11-7. [PMID: 21164177 DOI: 10.1093/mutage/geq078] [Citation(s) in RCA: 168] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Biological dosimetry, based on the analysis of micronuclei (MN) in the cytokinesis-block micronucleus (CBMN) assay can be used as an alternative method for scoring dicentric chromosomes in the field of radiation protection. Biological dosimetry or Biodosimetry, is mainly performed, in addition to physical dosimetry, with the aim of individual dose assessment. Many studies have shown that the number of radiation-induced MN is strongly correlated with dose and quality of radiation. The CBMN assay has become, in the last years, a thoroughly validated and standardised technique to evaluate in vivo radiation exposure of occupational, medical and accidentally exposed individuals. Compared to the gold standard, the dicentric assay, the CBMN assay has the important advantage of allowing economical, easy and quick analysis. The main disadvantage of the CBMN assay is related to the variable micronucleus (MN) background frequency, by which only in vivo exposures in excess of 0.2-0.3 Gy X-rays can be detected. In the last years, several improvements have been achieved, with the ultimate goals (i) of further increasing the sensitivity of the CBMN assay for low-dose detection by combining the assay with a fluorescence in situ hybridisation centromere staining technique, (ii) of increasing the specificity of the test for radiation by scoring nucleoplasmic bridges in binucleated cells and (iii) of making the assay optimally suitable for rapid automated analysis of a large number of samples, viz. in case of a large-scale radiation accident. The development of a combined automated MN-centromere scoring procedure remains a challenge for the future, as it will allow systematic biomonitoring of radiation workers exposed to low-dose radiation.
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Affiliation(s)
- Anne Vral
- Department of Basic Medical Sciences, Ghent University, De Pintelaan 185, 9000 Gent, Belgium.
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Dosimetric evaluation and therapeutic response to internal radiation therapy of hepatocarcinomas using iodine-131-labelled lipiodol. Nucl Med Commun 2008; 29:815-25. [DOI: 10.1097/mnm.0b013e32830439c6] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Garin E, Bourguet P. Intra-arterial Therapy of Liver Tumours. Clin Nucl Med 2008. [DOI: 10.1007/978-3-540-28026-2_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Song EY, Rizvi SMA, Qu CF, Raja C, Yuen J, Li Y, Morgenstern A, Apostolidis C, Allen BJ. The cytokinesis-block micronucleus assay as a biological dosimeter for targeted alpha therapy. Phys Med Biol 2007; 53:319-28. [PMID: 18184988 DOI: 10.1088/0031-9155/53/2/001] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Ionizing radiation causes structural chromosomal aberrations, a proportion of which give rise to chromosome fragments without spindle attachment organelles. When a cell divides, some of these fragments are excluded from the main daughter nuclei and form small nuclei within the cytoplasm. The cytokinesis-block micronucleus assay allows these micronuclei (MN) to be counted, providing an in situ biological dosimeter. In this study, we evaluated the micronucleus frequency in peripheral blood lymphocytes after in vitro incubation with the alpha conjugates (213)BiI(3) and (213)Bi-9.2.27 (AIC). Lymphocytes were inoculated in vitro AIC for 3 h. Further, we report the first MN measurements in melanoma patients after targeted alpha therapy (TAT) with (213)Bi-9.2.27. Patients were injected with 260-360 MBq of AIC, and blood samples taken at 3 h, 2 weeks and 4 weeks post-treatment. Absorbed dose (MIRD) and effective total body dose (PED) were calculated. The MN frequency in lymphocytes was similar for equal in vitro incubation activities of (213)BiI(3) and (213)Bi-9.2.27 (P=0.5), indicating that there is no selective targeting of lymphocytes by the alpha conjugates. After inoculation with 10-1200 kBq mL-1 of AIC, there was a substantial activity-related increase in MN. The number of MN in the blood of treated patients peaked at 3 h post-TAT, slowly returning to baseline levels by 4 weeks. The mean photon equivalent dose (PED) is 0.43 Gy (SD 0.15) and the mean MIRD calculated absorbed dose is 0.11 Gy (SD 0.03), giving an RBE=4+/-0.4 for this study.
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Affiliation(s)
- Emma Y Song
- Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah, Australia
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Gunvén P. Liver Embolizations in Oncology. A Review. Part II. Arterial Radioembolizations, Portal Venous Embolizations, Experimental Arterial Embolization Procedures. Med Oncol 2007; 24:287-96. [PMID: 17873303 DOI: 10.1007/s12032-007-0040-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2007] [Revised: 11/30/1999] [Accepted: 05/20/2007] [Indexed: 01/17/2023]
Abstract
Arterial embolization of the liver may temporarily retard the growth of its primary and secondary tumors which are both mainly nourished arterially. Addition of radioisotopes, mostly (131)I or (90)Y, results in radioembolizations which predominantly act by radiation and less by ischemia. They may therefore be utilized in the absence of portal venous flow when conventional embolization is hazardous. (131)I-oily radioembolization seems to prolong short-term survival in such patients with unresectable hepatocellular cancers, and to improve the prognosis after resection of hepatocellular cancer. The procedure does however not palliate better than "cold" chemoembolization in patients with preserved portal flow, except for having milder side effects. Embolization with (90)Y-coupled microspheres may shrink primary and secondary liver tumors but has so far unproven effects on survival. Embolization of portal venous branches gives compensatory hypertrophy of the non-embolized liver and can increase the volume of the future remnant liver before resection. This diminishes the risk for postoperative liver failure after extensive resection and/or in the presence of chronic liver disease, and permits wider surgical indications. Tumor growth may however be accelerated, and the hypertrophy is inhibited by severe liver parenchymal disease in which situation the method would be most needed. Experimental use of liver arterial embolizations includes combined arterial and portal embolizations, i.e. "chemical hepatectomy," arterial embolizations before external radiotherapy, administration of boron for neutron capture therapy, immunoembolizations, and future gene therapy.
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Affiliation(s)
- Peter Gunvén
- Department of Oncology, Radiumhemmet, Karolinska University Hospital at Solna, Stockholm 171 76, Sweden.
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Boucher E, Garin E, Guylligomarc'h A, Olivié D, Boudjema K, Raoul JL. Intra-arterial injection of iodine-131-labeled lipiodol for treatment of hepatocellular carcinoma. Radiother Oncol 2006; 82:76-82. [PMID: 17141900 DOI: 10.1016/j.radonc.2006.11.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2006] [Revised: 10/26/2006] [Accepted: 11/03/2006] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIM The therapeutic effect of intra-arterial injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma in palliative or adjuvant settings has been promising. We report, the results of an open study of this therapy in cirrhotic patients with small hepatocellular carcinoma. PATIENTS AND METHOD Forty patients with hepatocellular carcinoma were given intra-arterial injections of 131-iodine-labeled lipiodol. These injections were repeated if necessary every 3 months. Tumor response (WHO criteria) was determined on CT scans performed after each treatment and every 3 months during the follow-up. Side effects and the cause of death were recorded. Therapeutic response and survival were analyzed. RESULTS The median number of treatment was 2 (1-4). There was one complete response, 18 partial responses (47.5% response rate); 19 had stable disease and 2 progressions. Overall survival rates (+/-CI 95%) at 1, 2 and 3 years were: 90+/-4.7%, 60.3+/-8%, and 39+/-8.3%, respectively. Median survival was 27 months; 25 patients have died (4-56 months), 8 of tumor progression with a multifocal spread in the liver. Tolerance was good except for 2 patients who develop a fatal drug-related pulmonary insufficiency. CONCLUSION These data suggest that intra-arterial therapeutic injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma can provide high rate response and long survival for individuals not eligible for surgery or local treatment.
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Affiliation(s)
- Eveline Boucher
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
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Lambert B, Van de Wiele C. Treatment of hepatocellular carcinoma by means of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 2005; 32:980-9. [PMID: 16032439 DOI: 10.1007/s00259-005-1859-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Several techniques have been developed for radionuclide therapy of hepatocellular carcinoma (HCC). Medical literature databases (Pubmed, Medline) were screened for available literature and articles were critically analysed as to their scientific relevance. In a palliative setting, intra-arterial administration of 131I-Lipiodol yields responses in 17-92% of patients. According to a randomised study, 131I-Lipiodol was far better tolerated than classic chemo-embolisation. The additive value of a single 131I-Lipiodol administration following partial liver resection for HCC was evaluated and evidence is available that adjuvant radionuclide treatment reduces the recurrence rate. Data concerning the role of 131I-Lipiodol in bridging patient to liver transplantation are scarce but suggest a potential benefit in terms of reducing the drop-out rate while patients are listed for transplantation. 188Re- and 90Y-labelled conjugates are emerging and initial clinical data are promising. Treatment of HCC with 90Y-labelled microspheres is likely as efficacious as treatment with radiolabelled Lipiodol but pretreatment 99mTc-MAA scintigraphy is required in order to exclude patients with significant lung shunting. Several antibodies targeting antigens expressed on HCC have been radiolabelled, almost exclusively with 131I, and evaluated in a preclinical or clinical setting. The use of radiolabelled Lipiodol and microspheres allows for selective targeting of HCC with limited toxicity. Prospective, randomised controlled trials demonstrating that both treatment modalities may provide a survival benefit in a palliative setting are mandatory. In addition, future research should focus on the complementary role of radionuclide treatment in patients at risk for recurrent disease following partial liver resection or while awaiting liver transplantation.
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Affiliation(s)
- Bieke Lambert
- Nuclear Medicine Division, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium
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Thierens HM, Monsieurs MA, Bacher K. Patient dosimetry in radionuclide therapy: the whys and the wherefores. Nucl Med Commun 2005; 26:593-9. [PMID: 15942479 DOI: 10.1097/01.mnm.0000167910.76718.ad] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The importance and methodology of contemporary patient dosimetry in well-established radionuclide therapies are reviewed. The different protocols used for radioiodine treatment of thyrotoxicosis are discussed. Special attention is paid to patient dosimetry in the largest safe dose approach for curative radioiodine therapy of thyroid remnants and metastases in the post-surgical treatment of differentiated thyroid cancer. Nowadays, meta-[131I]iodobenzylguanidine (131I-MIBG) therapy for neuroblastoma relies on bone marrow dose levels. Issues related to whole-body and tumour dosimetry in this type of radionuclide therapy, where, traditionally, dosimetry has played an important role, are discussed. A relatively large number of patients are treated with radiolabelled Lipiodol for hepatocellular carcinoma. Administered activities are restricted to 2.22 GBq (60 mCi) when using 131I-lipiodol because of the radioprotection measures to be taken. These radiation protection issues can be avoided by using 188Re labelled Lipiodol allowing further dose escalation. The follow-up of these patients also necessitates whole-body dosimetry. It is concluded that for treatment of malignant diseases reliable patient dosimetry is now a keystone of high quality radionuclide therapy. Where dosimetry of present medical applications focuses generally on the critical organs, in the near future accurate 3-dimensional tumour dosimetry also will become feasible by the introduction of the combined SPECT-CT and PET-CT imaging systems in the dosimetric methodology. This will allow treatment protocols based on tumour dose prescriptions as performed in external beam radiotherapy.
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Affiliation(s)
- Hubert M Thierens
- Department of Medical Physics and Radiation Protection, University of Ghent, Belgium.
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Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985; 38:1393-406. [PMID: 2990661 DOI: 10.1007/s00259-011-1812-2] [Citation(s) in RCA: 157] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A total of 850 patients with hepatocellular carcinoma seen during the last 8 years were analyzed retrospectively for survival in relation to treatment and disease stage. A new staging scheme based on tumor size, ascites, jaundice and serum albumin was used. Clearly, the prognosis depended on disease stage. The median survival of 229 patients who received no specific treatment was 1.6 months, 0.7 month for Stage III patients, 2.0 months for Stage II, and 8.3 months for Stage I. The median survival of Stage I patients who had hepatic resection (n = 115) was 25.6 months and Stage II patients with resection (n = 42) was 12.2 months. In patients who had a small cancer (less than or equal to 25% of liver area in size) the median survival was 29.0 months. Survival of the surgically treated patients, which represented a highly selected group, was better than that of medically treated patients of a comparable stage. Median survival of Stage I medically treated patients (n = 124) was 9.4 months, for Stage II (n = 290) 3.5 months, and for Stage III (n = 50) 1.6 months. Medical treatment prolonged survival in Stage II and III patients, but not in Stage I. Transcatheter arterial embolization gave a better survival compared with chemotherapy, whether intra-arterial bolus administration of mitomycin C, systemic mitomycin C, or oral/rectal tegafur, in Stage II. Among various chemotherapeutic modalities, intra-arterial bolus injection was superior to systemic chemotherapy in survival in Stage II. In Stage III, chemotherapy improved survival as compared with no specific treatment. The major causes of death were hepatic failure and gastrointestinal bleeding, probably due to the coexistent advanced cirrhosis. These results in survival are much improved over the past reports, and the differences are probably a result of earlier diagnosis and frequent hepatic resections.
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