Targeted alpha therapy of mCRPC: Dosimetry estimate of (213)Bismuth-PSMA-617.
Targeted alpha therapy of mCRPC: Dosimetry estimate of (213)Bismuth-PSMA-617.
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DOI：
10.1007/s00259-017-3817-y
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发表时间：
2018-01
影响因子：
9.1
通讯作者：
Giesel FL
中科院分区：
文献类型：
--
作者：
Kratochwil C;Schmidt K;Afshar-Oromieh A;Bruchertseifer F;Rathke H;Morgenstern A;Haberkorn U;Giesel FL
PSMA-617是一种靶向前列腺特异性膜抗原（PSMA）的小分子。在这项工作中，我们估计的辐射剂量为这个配体标记的α-发射体213铋。三名患有转移性前列腺癌的患者在注射68 Ga-PSMA-617后0.1小时、1小时、2小时、3小时、4小时和5小时进行PET扫描。来源器官为肾脏、肝脏、脾脏、唾液腺、膀胱、红骨髓和代表性肿瘤病变。将成像核素68 Ga外推至213 Bi的半衰期。~（213）Bi的停留时间被转移到不稳定子体核素上。使用OLINDA进行剂量学计算。与225 Ac-PSMA-617的文献数据相比，对结果进行了讨论。假设α辐射的相对生物学效应为5，剂量测定估计值显示，唾液腺的平均等效剂量为8.1 Sv RBE 5/GBq，肾脏为8.1 Sv RBE 5/GBq，红骨髓为0.52 Sv RBE 5/GBq。肝脏（1.2 Sv RBE 5/GBq）、脾脏（1.4 Sv RBE 5/GBq）、膀胱（0.28 Sv RBE 5/GBq）和其他器官（0.26 Sv RBE 5/GBq）不具有剂量限制性。有效剂量为0.56 Sv RBE 5/GBq。肿瘤病变范围为3.2-9.0 SvRBE 5/GBq（中位数为7.6 SvRBE 5/GBq）。肾脏将累积治疗活性限制为3.7 GBq;红骨髓可能将最大单个分数限制为2 GBq。尽管结果令人鼓舞，但与225 Ac-PSMA-617相比，治疗指数较差。213 Bi-PSMA-617的剂量测定在传统上认为临床应用合理的范围内。然而，与225 Ac-PSMA-617相比，其具有更高的灌注依赖性脱靶辐射，并且PSMA-617在剂量限制性器官中的生物半衰期比213 Bi的物理半衰期更长，使得该核素成为前列腺癌的靶向α治疗的第二选择放射性标记。本文的在线版本（10.1007/s 00259 -017-3817-y）包含补充材料，可供授权用户使用。
PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter 213Bi. Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of 68Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide 68Ga was extrapolated to the half-life of 213Bi. The residence times of 213Bi were forwarded to the instable daughter nuclides. OLINDA was used for dosimetry calculation. Results are discussed in comparison to literature data for 225Ac-PSMA-617. Assuming a relative biological effectiveness of 5 for alpha radiation, the dosimetry estimate revealed equivalent doses of mean 8.1 Sv RBE5/GBq for salivary glands, 8.1 Sv RBE5/GBq for kidneys and 0.52 Sv RBE5/GBq for red marrow. Liver (1.2 Sv RBE5/GBq), spleen (1.4 Sv RBE5/GBq), bladder (0.28 Sv RBE5/GBq) and other organs (0.26 SvRBE5/GBq) were not dose-limiting. The effective dose is 0.56 Sv RBE5/GBq. Tumor lesions were in the range 3.2–9.0 SvRBE5/GBq (median 7.6 SvRBE5/GBq). Kidneys would limit the cumulative treatment activity to 3.7 GBq; red marrow might limit the maximum single fraction to 2 GBq. Despite promising results, the therapeutic index was inferior compared to 225Ac-PSMA-617. Dosimetry of 213Bi-PSMA-617 is in a range traditionally considered reasonable for clinical application. Nevertheless, compared to 225Ac-PSMA-617, it suffers from higher perfusion-dependent off-target radiation and a longer biological half-life of PSMA-617 in dose-limiting organs than the physical half-life of 213Bi, rendering this nuclide as a second choice radiolabel for targeted alpha therapy of prostate cancer. The online version of this article (10.1007/s00259-017-3817-y) contains supplementary material, which is available to authorized users.
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影响因子：
9.3
作者：
Kratochwil, Clemens;Giesel, Frederik L.;Haberkorn, Uwe
通讯作者：
Haberkorn, Uwe
影响因子：
20.3
作者：
Jurcic, JG;Larson, SM;Scheinberg, DA
通讯作者：
Scheinberg, DA
DOI：
10.1158/1078-0432.ccr-10-0382
发表时间：
2010-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Rosenblat TL;McDevitt MR;Mulford DA;Pandit-Taskar N;Divgi CR;Panageas KS;Heaney ML;Chanel S;Morgenstern A;Sgouros G;Larson SM;Scheinberg DA;Jurcic JG
通讯作者：
Jurcic JG
DOI：
10.1007/s00259-017-3657-9
发表时间：
2017-06
影响因子：
9.1
作者：
Sathekge M;Knoesen O;Meckel M;Modiselle M;Vorster M;Marx S
通讯作者：
Marx S
影响因子：
4.8
作者：
Li, Y;Tian, Z;Allen, BJ
通讯作者：
Allen, BJ