镥-PSMA-617单光子发射计算机断层扫描/计算机断层扫描剂量学和放射生物学模型表明，随着连续周期的进行，肿瘤与肾脏的剂量比在降低。

Lu-PSMA-617 Single-Photon Emission Computed Tomography/Computed Tomography Dosimetry and Radiobiological Models Demonstrate Decreasing Tumor-to-Kidney Dose Ratio With Successive Cycles.

作者信息

Fitzpatrick Kellen J, Mikell Justin K, Roseland Molly E, Niedbala Jeremy, Suresh Krithika, Peterson Avery B, Viglianti Benjamin L, Wong Ka Kit, Frey Kirk A, Dewaraja Yuni K

机构信息

Departments of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, Wayne State University, Detroit, Michigan.

Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.

出版信息

Int J Radiat Oncol Biol Phys. 2025 Jun 27. doi: 10.1016/j.ijrobp.2025.06.3869.

DOI:10.1016/j.ijrobp.2025.06.3869

PMID:40582602

Abstract

PURPOSE

Dosimetry studies following Lu-PSMA-617 radioligand therapy (RLT) for metastatic castration-resistant prostate cancer have focused primarily on absorbed dose (AD). Biologically effective dose (BED) and equieffective dose in 2 Gray fractions (EQD2) further account for dose delivery rate, tissue repair rate, and radiosensitivity. Our aims were to investigate cycle-to-cycle changes in tumor and organ AD, BED, and EQD2 and tumor-to-kidney dose ratio (TKR) for the given dose metric.

METHODS AND MATERIALS

Serial single-photon emission computed tomography/computed tomography imaging was performed after cycle 1 or cycles 1 and 2 of Lu-PSMA-617 RLT. BED and EQD2 were calculated using 2 sets of tumor radiobiological parameters: α/β = 3 Gy, T = 0.27 hours, proposed for prostate cancer, and α/β = 10 Gy, T = 1.5 hours, commonly used for other tumor types. Kidney parameters were α/β = 2.6 Gy and T = 2.8 hours. TKR was compared for patients with imaging after cycles 1 and 2. The relationship between cycle 1 whole-body tumor volume (WBTV) dose metrics and change in prostate-specific antigen (PSA) level was also investigated.

RESULTS

Ninety-one tumors were segmented in 20 patients with cycle 1 imaging; 10 also received imaging after cycle 2. Median (range) cycle 1 ADs were 17.7 (0.5-155.9) Gy to the tumor and 2.6 (0.5-10.0) Gy to the kidney. Tumor AD decreased from cycle 1 to 2, whereas organ AD remained constant. Median TKR decreased from 6.6 to 3.1 while TKR (α/β = 10 Gy) decreased from 9.0 to 4.3. For tumors receiving higher AD, the decrease in TKR with cycle was up to 30% greater when calculated with radiobiological models than with AD. Furthermore, a significant association between early PSA response and cycle 1 WBTV dose metrics was demonstrated (Spearman ρ = 0.63, P = .005).

CONCLUSIONS

A strong dose-response relationship was seen between cycle 1 WBTV dose metrics and a decrease in PSA. Radiobiological models can substantially impact the TKR and the cycle-to-cycle change in TKR and should be considered when investigating novel Lu-PSMA-617 RLT dosing schemas.

摘要

目的

对于转移性去势抵抗性前列腺癌，¹⁷⁷Lu-PSMA-617放射性配体疗法（RLT）后的剂量学研究主要集中在吸收剂量（AD）上。生物有效剂量（BED）和2 Gy分次等效剂量（EQD2）进一步考虑了剂量传递率、组织修复率和放射敏感性。我们的目的是研究给定剂量指标下肿瘤和器官的AD、BED和EQD2以及肿瘤与肾脏剂量比（TKR）在周期之间的变化。

方法和材料

在¹⁷⁷Lu-PSMA-617 RLT的第1周期或第1和第2周期后进行系列单光子发射计算机断层扫描/计算机断层扫描成像。使用两组肿瘤放射生物学参数计算BED和EQD2：α/β = 3 Gy，T = 0.27小时，为前列腺癌提出；α/β = 10 Gy，T = 1.5小时，常用于其他肿瘤类型。肾脏参数为α/β = 2.6 Gy和T = 2.8小时。比较第1和第2周期后成像患者的TKR。还研究了第1周期全身肿瘤体积（WBTV）剂量指标与前列腺特异性抗原（PSA）水平变化之间的关系。

结果

在20例进行第1周期成像的患者中分割出91个肿瘤；其中10例在第2周期后也接受了成像。第1周期肿瘤的中位（范围）AD为17.7（0.5 - 155.9）Gy，肾脏为2.6（0.5 - 10.0）Gy。肿瘤AD从第1周期到第2周期下降，而器官AD保持不变。中位TKR从6.6降至3.1，而TKR（α/β = 10 Gy）从9.0降至4.3。对于接受较高AD的肿瘤，与AD计算相比，使用放射生物学模型计算时，TKR随周期的下降幅度高达30%。此外，还证明了早期PSA反应与第1周期WBTV剂量指标之间存在显著关联（Spearman ρ = 0.63，P = .005）。