Targeted radiotherapy of pigmented melanoma with 131I-5-IPN
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 131I-N-(2-(diethylamino)ethyl)-5-(iodo-131I)picolinamide (131I-5-IPN)...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-12-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0983-0 |
| _version_ | 1819265498195427328 |
|---|---|
| author | Xiaodong Xu Lujie Yuan Yongkang Gai Qingyao Liu Lianglan Yin Yaqun Jiang Yichun Wang Yongxue Zhang Xiaoli Lan |
| author_facet | Xiaodong Xu Lujie Yuan Yongkang Gai Qingyao Liu Lianglan Yin Yaqun Jiang Yichun Wang Yongxue Zhang Xiaoli Lan |
| author_sort | Xiaodong Xu |
| collection | DOAJ |
| description | 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 131I-N-(2-(diethylamino)ethyl)-5-(iodo-131I)picolinamide (131I-5-IPN) and evaluate its therapeutic ability and toxicity as a radioiodinated melanin-targeting therapeutic agent. Methods The trimethylstannyl precursor was synthesized and labeled with 131I to obtain 131I-5-IPN. The pharmacokinetics of 131I-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 [131I]NaI; group D and E received one or two dose of 18.5 MBq 131I-5-IPN, respectively. TRNT efficacy was evaluated through tumor volume measurement and biology study. The toxic effects of 131I-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 131I-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 of 131I-5-IPN showed lasting high tumor uptake in pigmented B16F10 models for 72 h. TRNT with 131I-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. 131I-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 synthesized 131I-5-IPN, which presents long-time retention in melanotic melanoma. TRNT with 131I-5-IPN has the potential to be a safe and effective strategy for management of pigmented melanoma. |
| first_indexed | 2024-12-23T20:46:20Z |
| format | Article |
| id | doaj.art-28fff99dd5554f84a56d913c9d023454 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-23T20:46:20Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-28fff99dd5554f84a56d913c9d0234542022-12-21T17:31:47ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-12-0137111310.1186/s13046-018-0983-0Targeted radiotherapy of pigmented melanoma with 131I-5-IPNXiaodong Xu0Lujie Yuan1Yongkang Gai2Qingyao Liu3Lianglan Yin4Yaqun Jiang5Yichun Wang6Yongxue Zhang7Xiaoli Lan8Department of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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 131I-N-(2-(diethylamino)ethyl)-5-(iodo-131I)picolinamide (131I-5-IPN) and evaluate its therapeutic ability and toxicity as a radioiodinated melanin-targeting therapeutic agent. Methods The trimethylstannyl precursor was synthesized and labeled with 131I to obtain 131I-5-IPN. The pharmacokinetics of 131I-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 [131I]NaI; group D and E received one or two dose of 18.5 MBq 131I-5-IPN, respectively. TRNT efficacy was evaluated through tumor volume measurement and biology study. The toxic effects of 131I-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 131I-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 of 131I-5-IPN showed lasting high tumor uptake in pigmented B16F10 models for 72 h. TRNT with 131I-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. 131I-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 synthesized 131I-5-IPN, which presents long-time retention in melanotic melanoma. TRNT with 131I-5-IPN has the potential to be a safe and effective strategy for management of pigmented melanoma.http://link.springer.com/article/10.1186/s13046-018-0983-0MelanomaMelaninTargeted radionuclide therapyPicolinamide |
| spellingShingle | Xiaodong Xu Lujie Yuan Yongkang Gai Qingyao Liu Lianglan Yin Yaqun Jiang Yichun Wang Yongxue Zhang Xiaoli Lan Targeted radiotherapy of pigmented melanoma with 131I-5-IPN Journal of Experimental & Clinical Cancer Research Melanoma Melanin Targeted radionuclide therapy Picolinamide |
| title | Targeted radiotherapy of pigmented melanoma with 131I-5-IPN |
| title_full | Targeted radiotherapy of pigmented melanoma with 131I-5-IPN |
| title_fullStr | Targeted radiotherapy of pigmented melanoma with 131I-5-IPN |
| title_full_unstemmed | Targeted radiotherapy of pigmented melanoma with 131I-5-IPN |
| title_short | Targeted radiotherapy of pigmented melanoma with 131I-5-IPN |
| title_sort | targeted radiotherapy of pigmented melanoma with 131i 5 ipn |
| topic | Melanoma Melanin Targeted radionuclide therapy Picolinamide |
| url | http://link.springer.com/article/10.1186/s13046-018-0983-0 |
| work_keys_str_mv | AT xiaodongxu targetedradiotherapyofpigmentedmelanomawith131i5ipn AT lujieyuan targetedradiotherapyofpigmentedmelanomawith131i5ipn AT yongkanggai targetedradiotherapyofpigmentedmelanomawith131i5ipn AT qingyaoliu targetedradiotherapyofpigmentedmelanomawith131i5ipn AT lianglanyin targetedradiotherapyofpigmentedmelanomawith131i5ipn AT yaqunjiang targetedradiotherapyofpigmentedmelanomawith131i5ipn AT yichunwang targetedradiotherapyofpigmentedmelanomawith131i5ipn AT yongxuezhang targetedradiotherapyofpigmentedmelanomawith131i5ipn AT xiaolilan targetedradiotherapyofpigmentedmelanomawith131i5ipn |