Lutetium-177 [177Lu]-PSMA-617是一种靶向放射性配体，能结合到前列腺特异性膜抗原（PSMA）并向转移性前列腺癌输送放射线治疗。存在PSMA阴性/FDG阳性转移可排除患者接受该治疗的资格。生物学引导的放射治疗（BgRT）是一种利用肿瘤PET排放物指导外部束放射治疗模式。探讨了将BgRT和Lutetium-177 [177Lu]-PSMA-617联合用于PSMA阴性/FDG阳性转移性前列腺癌患者的可行性。回顾了所有因PSMA/FDG不一致而被排除于LuPSMA临床试验（ID：ANZCTR12615000912583）的患者。考虑的是一种假设的工作流程，其中PSMA阴性/FDG阳性的转移会接受BgRT治疗，而PSMA阳性的转移则接受Lutetium-177 [177Lu]-PSMA-617治疗。将PSMA阴性/FDG阳性肿瘤的总肿瘤体积（GTV）确定在FDG PET/CT扫描的CT组分上。如果（1）标准化SUV（nSUV），定义为GTV内最大SUV（SUVmax）与GTV向外扩展5毫米/10毫米/20毫米的平均SUV的比率大于预先设定的nSUV阈值，并且（2）扩展范围内无PET亲和力，则肿瘤被视为适合BgRT的。在接受Lutetium-177 [177Lu]-PSMA-617治疗的75名患者中，有6名患者因PSMA/FDG不一致而被排除，识别出了89个PSMA阴性/FDG阳性的靶标。GTV体积范围从0.3 cm3到186 cm3（中位数GTV体积= 4.3 cm3，IQR = 2.2 cm3-7.4 cm3）。GTV内的SUVmax范围在3至12之间（中位SUVmax = 4.8，IQR = 3.9-6.2）。对于nSUV≥3，所有GTV中有67％/54％/39％适合在5毫米/10毫米/20毫米内接受BgRT。骨和肺转移是BgRT的最佳候选治疗对象（40％/27％的所有适合在5毫米内接受BgRT的肿瘤都是骨/肺GTV）。合并的BgRT/Lutetium-177 [177Lu]-PSMA-617治疗对于PSMA/FDG不一致的转移性前列腺癌患者是可行的。版权所有©2023 Gaudreault，Chang，Hardcastle，Jackson，Kron，Hofman和Siva。

Lutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored.All patients excluded from the LuPSMA clinical trial (ID: ANZCTR12615000912583) due to PSMA/FDG discordance were retrospectively reviewed. A hypothetical workflow where PSMA-negative/FDG-positive metastases would be treated with BgRT whilst PSMA-positive metastases would be treated with Lutetium-177 [177Lu]-PSMA-617 was considered. Gross tumour volume (GTV) of PSMA-negative/FDG-positive tumours were delineated on the CT component of the FDG PET/CT scan. Tumours were deemed suitable for BgRT if (1) normalised SUV (nSUV), defined as the ratio of maximum SUV (SUVmax) inside the GTV to mean SUV inside a 5 mm/10 mm/20 mm margin expansion of the GTV, was larger than a pre-specified nSUV threshold and (2) there was no PET avidity inside the margin expansion.In 75 patients screened for Lutetium-177 [177Lu]-PSMA-617 treatment, 6 patients were excluded due to PSMA/FDG discordance and 89 PSMA-negative/FDG-positive targets were identified. GTV volumes ranged from 0.3 cm3 to 186 cm3 (median GTV volume = 4.3 cm3, IQR = 2.2 cm3 - 7.4 cm3). SUVmax inside GTVs ranged between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 - 6.2). With nSUV ≥ 3, 67%/54%/39% of all GTVs were suitable for BgRT within 5 mm/10 mm/20 mm from the tumour. Bone and lung metastases were the best candidates for BgRT (40%/27% of all tumours suitable for BgRT with nSUV ≥ 3 within 5 mm from the GTV were bone/lung GTVs).Combined BgRT/Lutetium-177 [177Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.Copyright © 2023 Gaudreault, Chang, Hardcastle, Jackson, Kron, Hofman and Siva.