@misc{oai:repo.qst.go.jp:00066581,
 author = {Jiang, Cuiping and Xie, Lin and Hanyu, Masayuki and Zhang, Yiding and Azuma, Rikako and Suzuki, Hisashi and Shimokawa, Takashi and Wakizaka, Hidekatsu and Zang, Shiming and Wang, Feng and Zhang, Ming-Rong and 謝 琳 and 破入 正行 and 張 一鼎 and 東 梨佳子 and 鈴木 寿 and 下川 卓志 and 脇坂 秀克 and 張 明栄},
 month = {Oct},
 note = {Purpose: Checkpoint blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) boosts anti-tumor T cell immunity and results in markedly clinical responses in diverse tumor types, including melanoma. Anti-CTLA4 monoclonal antibody (mAb) is the first immune checkpoint inhibitor approved by US Food and Drug Administration (FDA), but its in vivo action is still under investigation. Herein, to noninvasively track and quantify the distribution and action of anti-CTLA4 mAb, we developed 64Cu-anti-CTLA4 mAb ( [64Cu]1) as a novel radiotracer to investigate its pharmacokinetics in the whole bodies of mice. 
Method: [64Cu]1 was synthesized by labeling DOTA-anti-CTLA4 mAb with 64Cu. Biodistribution and small-animal PET scans were performed at 1 h, 24 h, 48 h, 72 h after [64Cu]1 injection into immunocompetent C57BL/6 mice bearing B16F10 melanoma.  
Result: [64Cu]1 carried through the blood (28.1 % ID/g) to heart (4.7 % ID/g), lung (6.2 % ID/g), and kidney (7.5 % ID/g) at 1 h after injection, followed by a rapid distribution throughout the whole body. Sustained high radioactivity accumulated in the liver from 1 h (18.3 % ID/g) to 48 h (13.9 % ID/g) after [64Cu]1 injection. The lowest radioactivity was found in the muscle (0.7 % ID/g) and brain (0.8 % ID/g). For the immune organs, [64Cu]1 achieved excellent penetration in gut-associated lymphoid tissue (GALT), reached the highest uptake at 1 h (7.7 % ID/g), 24 h (93.3 % ID/g, 48 h (44.6 % ID/g), higher uptake in spleen at 1 h (17.8 % ID/g), 24 h (17.4 % ID/g), 48 h (12.7 % ID/g), relatively constant uptake in thymus (1.5-2.4 % ID/g). In B16F10 tumors, high accumulation of anti-CTLA4 mAb was shown at 24 h (7.3 % ID/g) and retention at 48 h (5.4 % ID/g). At 72 h after injection,  [64Cu]1 was rem                                                                                                                                         oved by hepatobiliary and renal clearance, generating a low radioactivity in the liver (4.3 % ID/g), intestine (1.0 % ID/g) and kidney (3.9 % ID/g), with background radioactivity in the other organs (1.1-5.4 % ID/g).  The three-dimensional PET imaging confirmed the biodistribution pattern of [64Cu]1, supporting digital reconstruction and quantification of its pharmacokinetics in spleen, GALT, B16F10 tumors and other organs and tissue in a noninvasive and temporal-spatial pattern.
Conclusion: This study determined the pharmacokinetics of CTLA4 mAb in mice bearing melanoma, which would be helpful for facilitating the development of anti-CTLA4 mAb immunotherapy., Japan-China Nuclear Medicine Exchange Meeting},
 title = {Biodistribution and PET imaging study of 64Cu-anti-CTLA4 mAb in melanoma bearing mice},
 year = {2017}
}