Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC.

PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties.

Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120-160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers.

[177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased.

Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.

European journal of nuclear medicine and molecular imaging. 2020 Sep 19 [Epub ahead of print]

Vasko Kramer, René Fernández, Wencke Lehnert, Luis David Jiménez-Franco, Cristian Soza-Ried, Elisabeth Eppard, Matias Ceballos, Marian Meckel, Martina Benešová, Christoph A Umbricht, Andreas Kluge, Roger Schibli, Konstantin Zhernosekov, Horacio Amaral, Cristina Müller

Center for Nuclear Medicine & PET/CT Positronmed, Julio Prado 714, 7501068, Providencia, Santiago, Chile. ., Center for Nuclear Medicine & PET/CT Positronmed, Julio Prado 714, 7501068, Providencia, Santiago, Chile., ABX-CRO, 01307, Dresden, Germany., Positronpharma SA, 7500921, Providencia, Santiago, Chile., ITM Medical Isotopes GmbH, Munich, Germany., Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland.

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