1. Targeted radiotherapy of pigmented melanoma with 131 I-5-IPN.
- Author
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Xu X, Yuan L, Gai Y, Liu Q, Yin L, Jiang Y, Wang Y, Zhang Y, and Lan X
- Subjects
- Amides administration & dosage, Amides chemistry, Animals, Humans, Male, Melanoma pathology, Melanoma, Amelanotic radiotherapy, Melanoma, Experimental pathology, Melanoma, Experimental radiotherapy, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Picolinic Acids chemistry, Radiation Dosage, Random Allocation, Skin Neoplasms radiotherapy, Iodine Radioisotopes administration & dosage, Melanoma radiotherapy, Picolinic Acids administration & dosage, Radiopharmaceuticals administration & dosage
- Abstract
Purpose: There has been no satisfactory treatment for advanced melanoma until now. Targeted radionuclide therapy (TRNT) may be a promising option for this heretofore lethal disease. Our goal in this study was to synthesize
131 I-N-(2-(diethylamino)ethyl)-5-(iodo-131I)picolinamide (131 I-5-IPN) and evaluate its therapeutic ability and toxicity as a radioiodinated melanin-targeting therapeutic agent., Methods: The trimethylstannyl precursor was synthesized and labeled with131 I to obtain131 I-5-IPN. The pharmacokinetics of131 I-5-IPN was evaluated through SPECT imaging, and its biodistribution was assessed in B16F10 tumor models and in A375 human-to-mouse xenografts. For TRNT, B16F10 melanoma-bearing mice were randomly allocated to receive one of five treatments (n = 10 per group): group A (the control group) received 0.1 mL saline; group B was treated with an equimolar dose of unlabeled precursor; group C received 18.5 MBq of [131 I]NaI; group D and E received one or two dose of 18.5 MBq131 I-5-IPN, respectively. TRNT efficacy was evaluated through tumor volume measurement and biology study. The toxic effects of131 I-5-IPN on vital organs were assessed with laboratory tests and histopathological examination. The radiation absorbed dose to vital organs was estimated based on biodistribution data., Results:131 I-5-IPN was successfully prepared with a good radiochemistry yield (55% ± 5%, n = 5), and it exhibited a high uptake ratio in melanin-positive B16F10 cells which indicating high specificity. SPECT imaging and biodistribution of131 I-5-IPN showed lasting high tumor uptake in pigmented B16F10 models for 72 h. TRNT with131 I-5-IPN led to a significant anti-tumor effect and Groups D and E displayed an extended median survival compared to groups A, B, and C. The highest absorbed dose to a vital organ was 0.25 mSv/MBq to the liver; no obvious injury to the liver or kidneys was observed during treatment.131 I-5-IPN treatment was associated with reduction of expression of proliferating cell nuclear antigen (PCNA) and Ki67 and cell cycle blockage in G2/M phase in tumor tissues. Decreased vascular endothelial growth factor and CD31 expression, implying reduced tumor growth, was noted after TRNT., Conclusion: We successfully synthesized131 I-5-IPN, which presents long-time retention in melanotic melanoma. TRNT with131 I-5-IPN has the potential to be a safe and effective strategy for management of pigmented melanoma.- Published
- 2018
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