Dosimetric analysis reveals rapid clearance and low absorbed dose of [¹⁷⁷Lu]Lu-PSMA-617 in non-prostate cancers with high PSMA expression

BACKGROUND: The aim of this study was to evaluate the dosimetry for [177Lu]Lu-PSMA-617 in advanced non-prostate cancer (non-PCa) patients with previous intense radiotracer uptake of the tumor lesions on PET/CT using [68Ga]Ga-PSMA-11. RESULTS: Dosimetry data of 5 patients with non-prostate cancer (non-PCa group) were assessed and compared; Non-PCa tumors were breast cancer (BC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and anaplastic astrocytoma (AA). Five patients with metastatic castration-resistant prostate cancer (PCa group) were used as control-group. All patients were given [177Lu]Lu-PSMA-617 after proven sufficient PSMA uptake of tumor lesions by [68Ga]Ga-PSMA-11 PET/CT. Post-therapeutic dosimetry with serial whole-body scans (24, 48 and 72–120 h post-injection) included calculation of effective half-life and absorbed doses for tumor and non-tumor lesions and comparison between non-PCa and PCa patients. The mean effective half-life in tumor lesions was significantly shorter in non-PCa compared to PCa patients (27.1 ± 13.1 h vs. 74.9 ± 23.1 h, respectively, p < 0.001). Likewise, the mean absorbed dose per injected activity was significantly lower in tumor lesions of non-PCa compared to PCa (0.49 ± 0.40 Gy/GBq vs. 3.51 ± 2.20 Gy/GBq, respectively, p < 0.001). No significant differences for the source organ absorbed dose or effective half-life were observed between both groups. CONCLUSIONS: In non-prostate malignancy with impressive diagnostic PSMA-mediated tumor uptake, i.e. high tracer uptake at early time points in [68Ga]Ga-PSMA-11 PET/CT, [177Lu]Lu-PSMA-617 delivers a low tumor-absorbed dose due to a short effective half-life, therefore this therapy does not appear to be a potential antitumor option.