論文 - 詳細
| RRC ID | 52549 |
|---|---|
| 著者 | Zhu WJ, Kobayashi M, Yamada K, Nishi K, Takahashi K, Mizutani A, Nishii R, Flores LG 2nd, Shikano N, Kunishima M, Kawai K. |
| タイトル | Development of radioiodine labeled acetaminophen for specific, high-contrast imaging of malignant melanoma. |
| ジャーナル | Nucl Med Biol |
| Abstract |
INTRODUCTION:Due to its poor prognosis, specific imaging for early detection of malignant melanoma is strongly desired. Although radioiodine labeled 4-hydroxyphenylcysteamine, which we previously developed, has good affinity for tyrosinase, an enzyme in the melanin metabolic pathway, image contrast of the melanoma:organ ratios is not sufficiently high for detection of primary melanoma and metastases at early injection times. In this study, we developed radioiodine labeled acetaminophen (I-AP) for specific, high-contrast imaging of malignant melanoma. METHODS:Radioiodine-125-labeled AP (125I-AP) was prepared using the chloramine-T method under no carrier-added conditions. Accumulation of radioactivity and the mechanism were evaluated in vitro using B16 melanoma cells incubated with 125I-AP or 14C(U)-labeled AP (14C-AP) with and without l-tyrosine as a substrate of tyrosinase, phenylthiourea as an inhibitor of tyrosinase, and thymidine as an inhibitor of DNA polymerase. The biological distribution of radioactivity in B16 melanoma-bearing mice was evaluated to determine the accumulation of 125I-AP. The stability of 125I-AP over time was evaluated in mice. RESULTS:The labeling efficiency and radiochemical purity of 125I-AP were >80% and 95%, respectively. Accumulation of 125I-AP was higher than that of 14C-AP at 60 min of incubation in vitro. The affinity of 14C-AP for tyrosinase and DNA polymerase was higher than that of 125I-AP, whereas the Vmax of 125I-AP was higher than that of 14C-AP. 125I-AP showed the highest accumulation in the gall bladder, and clearance from the blood and kidney was rapid. Melanoma:muscle and melanoma:normal skin ratios of 125I-AP for imaging contrast were the highest at 15 min after injection, whereas the melanoma:blood and melanoma:bone ratios gradually increased over time. 125I-AP remained stable for 60 min after injection in mice. CONCLUSIONS:125I-AP has affinity for tyrosinase and high image contrast at early time points after injection. Therefore, 123I-AP imaging has great potential for specific, high-contrast detection of malignant melanoma. ADVANCES IN KNOWLEDGE: 123I-AP will provide specific, high-contrast imaging for malignant melanoma at early injection times. IMPLICATIONS FOR PATIENT CARE: 123I-AP has good potential for the diagnosis of malignant melanoma compared with 123I-labeled 4-hydroxyphenylcysteamine, which we previously developed. |
| 巻・号 | 59 |
| ページ | 16-21 |
| 公開日 | 2018-4-1 |
| DOI | 10.1016/j.nucmedbio.2017.12.008 |
| PII | S0969-8051(17)30231-7 |
| PMID | 29413752 |
| MeSH | Acetaminophen / chemistry* Acetaminophen / pharmacokinetics Animals Iodine Radioisotopes* Isotope Labeling Male Melanoma, Experimental / diagnostic imaging* Melanoma, Experimental / metabolism Mice Molecular Imaging / methods* Tissue Distribution |
| IF | 2.396 |
| 引用数 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | B16 melanoma(RCB1283) |