Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy.
Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy.
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DOI：
10.1007/s00259-014-2713-y
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发表时间：
2014-07
影响因子：
9.1
通讯作者：
Haberkorn, Uwe
中科院分区：
文献类型：
--
作者：
Zechmann, Christian M.;Afshar-Oromieh, Ali;Armor, Tom;Stubbs, James B.;Mier, Walter;Hadaschik, Boris;Joyal, John;Kopka, Klaus;Debus, Juergen;Babich, John W.;Haberkorn, Uwe
关键词：
由于前列腺特异性膜抗原（PSMA）在前列腺癌（PCa）中经常过表达，一些PSMA靶向分子正在开发中，以检测和治疗转移性去势抵抗性前列腺癌（mCRPC）。我们研究了PSMA小分子抑制剂((S)-2-(3-(S)-1-羧基-5-（3-（4-[124I]碘苯基）脲基）戊二酸的组织动力学；MIP-1095)使用PET/CT评估131I-MIP-1095在mCRPC男性患者中的潜在治疗用途的辐射剂量。我们还报告了前28例连续患者在同情使用方案下使用单周期131I-MIP-1095治疗的初步安全性和有效性。16例已知前列腺癌患者在静脉注射124I-MIP-1095（平均活性：67.4 MBq）后进行PET/CT成像。每位患者在注射后1、4、24、48和72小时使用PET/CT扫描多达5次。在每个时间点定义肿瘤病变和正常器官的兴趣体积，然后使用OLINDA/EXM软件计算剂量。28名mCRPC患者接受单周期131I-MIP-1095治疗（平均活度：4.8 GBq，范围2至7.2 GBq），并随访安全性和有效性。基线和随访检查包括全血细胞计数、肝肾功能检查和血清PSA测定。I-124-MIP-1095 PET/CT图像显示良好的肿瘤摄取，肝脏、近端肠和注射后几小时内肾脏也有中度摄取。仅在唾液腺和泪腺中观察到高摄取值。I-131-MIP-1095的剂量学估计显示，唾液腺（3.8 mSv/MBq）、肝脏（1.7 mSv/MBq）和肾脏（1.4 mSv/MBq）的吸收剂量最高。红骨髓的吸收剂量为0.37 mSv/MBq。60.7%接受治疗的男性的PSA值下降了50%。在患有骨痛的男性中，84.6%的人疼痛完全或中度减轻。血液学毒性轻微。在接受治疗的男性中，25%的人有短暂的轻微到中度口干。未观察到对肾功能的不良影响。基于psma靶向小分子124I-MIP-1095治疗的生物分布和剂量计算，与真正的类似物131I-MIP-1095能够以前所未有的剂量靶向肿瘤治疗肿瘤病变。受累淋巴结和骨转移暴露于估计吸收剂量超过300戈瑞。本文的在线版本（doi:10.1007/s00259-014-2713-y）包含补充资料，仅供授权用户使用。
Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[124I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of 131I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of 131I-MIP-1095. Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of 124I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of 131I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA. I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed. Based on the biodistribution and dose calculations of the PSMA-targeted small molecule 124I-MIP-1095 therapy with the authentic analog 131I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy. The online version of this article (doi:10.1007/s00259-014-2713-y) contains supplementary material, which is available to authorized users.
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影响因子：
8.8
作者：
Bourke, L.;Kirkbride, P.;Hooper, R.;Rosario, A. J.;Chico, T. J. A.;Rosario, D. J.
通讯作者：
Rosario, D. J.
影响因子：
45.3
作者：
Milowsky, MI;Nanus, DM;Bander, NH
通讯作者：
Bander, NH
影响因子：
11.5
作者：
Vallabhajosula, S;Goldsmith, SJ;Bander, NH
通讯作者：
Bander, NH
影响因子：
6.4
作者：
Mhawech-Fauceglia, P.;Zhang, S.;Penetrante, R.
通讯作者：
Penetrante, R.
影响因子：
6.6
作者：
Litwin, MS;Pasta, DJ;Carroll, PR
通讯作者：
Carroll, PR