Biodistribution and dosimetry of [177Lu]Lu-SibuDAB in patients with metastatic castration-resistant prostate cancer

Several prostate-specific membrane antigen (PSMA) radiopharmaceuticals have been used for the treatment of metastatic, castration-resistant prostate cancer (mCRPC). In an attempt to improve the tumour accumulation, new PSMA ligands were developed with an albumin-binding entity to enhance the blood circulation and, hence, tumour accumulation. In preclinical studies, [ 177 Lu]Lu-SibuDAB, a radiopharmaceutical with moderate albumin-binding properties, outperformed [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T. The aim of this study was to evaluate the dosimetry of [ 177 Lu]Lu-SibuDAB in patients diagnosed mCRPC. Seventeen patients (median age 72 years, range 63‒83) diagnosed with progressive disease of mCRPC were included in this prospective study after exhausting all available treatment options. They were injected with 5.3 ± 0.5 GBq (mean ± standard deviation) [ 177 Lu]Lu-SibuDAB as a first treatment cycle. Sixteen of these patients underwent sequential whole-body SPECT/CT and activity determination in venous blood samples for dosimetry purposes. Absorbed doses to the salivary glands, liver, spleen, kidneys, and red marrow as well as selected tumour lesions were calculated in OLINDA/EXM™ and compared to published values for previously established PSMA radiopharmaceuticals. Absorbed dose coefficients (ADC) to tumours (9.9 ± 5.4 Gy/GBq) were about 2-fold higher than those reported for clinically approved PSMA radiopharmaceuticals. ADC to salivary glands, liver, spleen, kidneys and red marrow were higher (0.5 ± 0.2, 0.2 ± 0.05, 0.2 ± 0.1, 1.8 ± 0.6, 0.1 ± 0.04 Gy/GBq, respectively) than for [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T, but lower than for [ 177 Lu]Lu-PSMA-ALB-56, a previously investigated long-circulating PSMA radiopharmaceutical. The tumour-to-kidneys, tumour-to-red marrow, tumour-to-salivary glands ADC ratio were 6.6, 102, 33.1. These ratios were comparable to those of [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T for kidneys and red-marrow, but higher for salivary glands. [ 177 Lu]Lu-SibuDAB showed a prolonged blood circulation time and, hence, a significantly increased absorbed tumour dose, while tumour-to-organ ADC ratios were similar to conventional PSMA radiopharmaceuticals. Further clinical investigations to evaluate the efficacy and safety of [ 177 Lu]Lu-SibuDAB are, thus, warranted.