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Abstract

Background

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, [¹⁷⁷Lu]Lu-SibuDAB, a radiopharmaceutical with moderate albumin-binding properties, outperformed [¹⁷⁷Lu]Lu-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-I&T. The aim of this study was to evaluate the dosimetry of [¹⁷⁷Lu]Lu-SibuDAB in patients diagnosed mCRPC.

Methods

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) [¹⁷⁷Lu]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.

Results

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 [¹⁷⁷Lu]Lu-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-I&T, but lower than for [¹⁷⁷Lu]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 [¹⁷⁷Lu]Lu-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-I&T for kidneys and red-marrow, but higher for salivary glands.

a) Maximum-intensity projections of SPECT images of [¹⁷⁷Lu]Lu-SibuDAB patient #5 (medium total tumour uptake) and patient #2 (low total tumour uptake), windowing at all timepoints was adjusted so that bottom (white) is 0 counts and top (black) is 1000 counts; b) TACs for tumours and kidneys, expressed as percent injected activity per gram (% IA/g) for patient #5; c) TACs for salivary glands, liver, spleen and red marrow (blood) (% IA/g) for patient #5. For better visualization, the initial peak of blood TAC is not shown. P = patient, p.i. = post injection; TAC = Time-activity curve

Conclusion

[¹⁷⁷Lu]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 [¹⁷⁷Lu]Lu-SibuDAB are, thus, warranted.

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