Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York;
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
J Nucl Med. 2023 Nov;64(11):1779-1787. doi: 10.2967/jnumed.123.265763. Epub 2023 Aug 31.
A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUV). After a second cycle of [Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUV as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm The median lesion-absorbed dose (AD) from the first cycle of [Lu]Lu-PSMA-617 RPT (AD) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUV and SPECT SUV ( = 0.005), 0.74 ( = 0.046) between the baseline PET SUV and the lesion AD, and -0.81 ( = 0.022) between the lesion AD and the percent change in PET SUV (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUV (baseline to post) was -0.88 ( = 0.007). Two cycles of [Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.
一项单机构前瞻性临床试验旨在证明联合 [Lu]Lu-PSMA-617 放射性药物治疗 (RPT) 和立体定向体部放射治疗 (SBRT) 治疗寡转移性去势敏感前列腺癌的可行性。6 名 9 处前列腺特异性膜抗原 (PSMA) 阳性寡转移灶的患者接受了 2 个周期的 [Lu]Lu-PSMA-617 RPT 治疗，随后进行 SBRT。在第一次静脉注射 [Lu]Lu-PSMA-617（7.46 ± 0.15GBq）后，患者在 3.2 ± 0.5、23.9 ± 0.4 和 87.4 ± 0.12.0 h 时进行 SPECT/CT。使用来自内部体模实验的校准因子（11.7 计数/秒/MBq）和恢复系数进行基于体素的剂量测定。在基线 PSMA PET/CT（50%SUV）上对病变进行分段。在第二个周期的 [Lu]Lu-PSMA-617（44 ± 3 d；7.50 ± 0.10 GBq）和临时 PSMA PET/CT 扫描后，所有 PSMA 阳性寡转移灶均接受 SBRT（27 Gy 分 3 次），随后进行 PSMA PET/CT 后处理。RPT 和 SBRT 体素剂量图按比例缩放（α/β=3Gy；修复半衰期，1.5h），以计算生物有效剂量（BED）。所有患者均无并发症完成联合治疗。未观察到 3+级毒性。PSMA PET 测量的病变 SUV 中位数为 16.8（四分位距 [IQR]，11.6）（基线）、6.2（IQR，2.7）（中期）和 2.9（IQR，1.4）（后）。PET 衍生的病变体积为 0.4-1.7 cm。从第一周期的 [Lu]Lu-PSMA-617 RPT（AD）获得的病变吸收剂量（AD）中位数为 27.7 Gy（范围，8.3-58.2 Gy；对应于 3.7 Gy/GBq，范围，1.1-7.7 Gy/GBq），而 SBRT 的病变 AD 中位数为 28.1 Gy（范围，26.7-28.8 Gy）。Spearman 秩相关系数 ρ 为 0.90，基线病变 PET SUV 与 SPECT SUV（ = 0.005），0.74（ = 0.046）之间为基线 PET SUV 与病变 AD，-0.81（ = 0.022）之间为病变 AD 与 PET SUV 的百分比变化（基线至中期）。RPT 和 SBRT 的病变 BED 中位数为 159 Gy（范围，124-219 Gy）。RPT 和 SBRT 的 BED 与 PET SUV 的百分比变化（从基线到后期）之间的 ρ 为-0.88（ = 0.007）。两个周期的 [Lu]Lu-PSMA-617 RPT 对 RPT 和 SBRT 的最大 BED 贡献约为 40%。寡转移性去势敏感前列腺癌患者接受 [Lu]Lu-PSMA-617 RPT 联合 SBRT 的病变部位剂量测定是可行的。联合 RPT 和 SBRT 可能是一种有效的方法，可以最大限度地将有意义的剂量输送给寡转移病灶，同时解决潜在的微小病灶储库，并限制正常组织的剂量暴露。
