Lee Hwan
University of Pennsylvania Perelman School of Medicine, Department of Radiology, Philadelphia, United States.
Mol Imaging Radionucl Ther. 2022 Feb 2;31(1):1-6. doi: 10.4274/mirt.galenos.2021.63308.
Radionuclide therapy targeting prostate-specific membrane antigen (PSMA) with alpha-emitting Ac-PSMA-617 has shown clinical efficacy even in cases of failed therapy with beta-emitting Lu-PSMA-617. We investigated the efficacy of Ac-PSMA-617 relative to Lu-PSMA-617 using subcellular dosimetry.
A 3-dimensional model of prostate cancer was constructed. For each decay, the absorbed and equivalent radiation dose to the cell nuclei was calculated. The relative efficacy per administered activity was calculated by taking into account the differences in residence time and tumor uptake.
As the tumor size increased, the absorbed dose from Ac-PSMA-617 increased linearly (R2: 0.99) and reached an asymptote near the maximum alpha range (85 µm), whereas the absorbed dose from Lu-PSMA-617 continued to increase linearly (R2: 0.99). The equivalent dose per decay was 2,320, 2,900, and 823-fold higher in favor of Ac-PSMA-617 compared to Lu-PSMA-617 in a single cell, 100 µm-radius micrometastasis, and macroscopic tumor, respectively. Per administered activity, the relative efficacy of Ac-PSMA-617 compared to Lu-PSMA-617 in respective tumor sizes was at least 3,480, 4,350, and 1,230-fold higher, and possibly 11,800, 14,900, and 4,200-fold higher considering differences in tumor uptake.
At commonly administered 1,000-fold lower activity of Ac-PSMA-617 relative to Lu-PSMA-617, the equivalent radiation dose deposited by Ac-PSMA-617 is higher in measurable disease and much higher in microscopic disease compared to Lu-PSMA-617.
靶向前列腺特异性膜抗原（PSMA）的放射性核素疗法使用发射α粒子的Ac-PSMA-617，即便在发射β粒子的Lu-PSMA-617治疗失败的病例中也已显示出临床疗效。我们使用亚细胞剂量测定法研究了Ac-PSMA-617相对于Lu-PSMA-617的疗效。
构建了前列腺癌的三维模型。对于每次衰变，计算细胞核的吸收辐射剂量和当量辐射剂量。通过考虑停留时间和肿瘤摄取的差异，计算每给药活度的相对疗效。
随着肿瘤大小增加，Ac-PSMA-617的吸收剂量呈线性增加（R2：0.99），并在接近最大α粒子射程（85μm）处达到渐近线，而Lu-PSMA-617的吸收剂量继续呈线性增加（R2：0.99）。在单细胞、半径100μm的微转移灶和肉眼可见肿瘤中，与Lu-PSMA-617相比，每次衰变的当量剂量有利于Ac-PSMA-617，分别高出2320倍、2900倍和823倍。就每给药活度而言，在各自肿瘤大小中，Ac-PSMA-617相对于Lu-PSMA-617的相对疗效至少高出3480倍、4350倍和1230倍，考虑到肿瘤摄取差异，可能高出11800倍、14900倍和4200倍。
相对于Lu-PSMA-617，Ac-PSMA-617的给药活度通常低1000倍，在可测量疾病中，Ac-PSMA-617沉积的当量辐射剂量高于Lu-PSMA-617，在微小疾病中则远高于Lu-PSMA-617。
