Evaluation of cytological radiation damage to lymphocytes after I-131 metaiodobenzylguanidine therapy by the cytokinesis
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ORIGINAL ARTICLE
Evaluation of cytological radiation damage to lymphocytes after I-131 metaiodobenzylguanidine therapy by the cytokinesis-blocked micronucleus assay Naoto Watanabe1 • Kunihiko Yokoyama2 • Seigo Kinuya3 • Hisao Tonami1
Received: 1 March 2016 / Accepted: 27 June 2016 Ó The Japanese Society of Nuclear Medicine 2016
Abstract Objective The purpose of this study was to evaluate the degree of cytological radiation damage to lymphocytes occurring after I-131 metaiodobenzylguanidine (MIBG) therapy as determined by the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by I-131 in vivo should result in augmentation of the number of cells with micronuclei. Methods We studied 15 patients with pheochromocytoma (14/15) or ganglioneuroma (1/15), who were treated initially with 7.4 GBq of I-131-MIBG. Isolated lymphocytes collected from patients 10 days after the therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. Serial blood samples were obtained periodically only from two patients for 2 years after therapy. Micronucleus number of micronuclei per 500 binucleated cells was scored by visual inspection. As controls, lymphocytes from the same patients before the therapy were also studied. In an in vitro study, lymphocytes from eight normal volunteers were exposed to doses varying from 0.5 to 2 Gy and studied with the same method. Results The mean number (mean ± SD) of micronuclei after treatment was significantly increased (p \ 0.001) as
& Naoto Watanabe [email protected] 1
Department of Radiology, Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku, Ishikawa 920-0293, Japan
2
Department of Nuclear Medicine, Public Central Hospital of Matto Ishikawa, Kuramitsu 3-8, Hakusan, Ishikawa 924-0865, Japan
3
Department of Nuclear Medicine, Kanazawa University, Takaramachi 13-1, Kanazawa, Ishikawa 920-8641, Japan
compared to control subjects (49.4 ± 8.2 vs. 11.3 ± 6.4). Internal radiation absorbed doses estimated for the 15 patients were 1.6 ± 0.3 Gy in this external irradiation study. The frequency of micronuclei post-administration of I-131-MIBG gradually decreased to near baseline (i.e., pretherapy) levels by 2 years. Conclusions The relatively low frequency of lymphocyte micronuclei induced by I-131-MIBG in vivo and reversal of the increasing frequency of lymphocyte micronuclei after therapy suggest that the short-term non-stochastic damage induced by this therapy with 7.4 GBq of I-131MIBG in pheochromocytoma or ganglioneuroma patients is limited and reversible. Keywords Micronucleus assay MIBG therapy Radiotoxicity Lymphocyte
Introduction Pheochromocytomas are rare neoplasms that constitute only about 0.1 % of the causes of hypertension. These tumors derive importance from their sometimes dramatic clinical presentation resulting from secreted neurohormones, and by often being treated by surgical excision. Included in the category of pheochromocytomas are the paraganglioma tumors, having similar clinical profil
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