1. Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC.
- Author
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Kramer, Vasko, Fernández, René, Lehnert, Wencke, Jiménez-Franco, Luis David, Soza-Ried, Cristian, Eppard, Elisabeth, Ceballos, Matias, Meckel, Marian, Benešová, Martina, Umbricht, Christoph A., Kluge, Andreas, Schibli, Roger, Zhernosekov, Konstantin, Amaral, Horacio, and Müller, Cristina
- Subjects
COMPUTED tomography ,HIGH dose rate brachytherapy ,RADIATION dosimetry ,CASTRATION-resistant prostate cancer ,DRUG efficacy ,PROSTATE cancer patients ,CHROMIUM isotopes ,PROSTATE-specific antigen - Abstract
Introduction: 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 [
177 Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. Methods: Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177 Lu]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. Results: [177 Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177 Lu]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 [177 Lu]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. Conclusion: 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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