Minimizing the dose limiting salivary gland uptake for the endoradiotherapy of prostate cancer
Nuclear Medicine, Radiotherapy, Radiobiology
Final Report Abstract
Endoradiotherapy with radioactive labeled PSMA inhibitors, has emerged as a promising treatment modality for patients with advanced prostate cancer. However, a notable limitation of this therapy is the substantial accumulation of radioactive tracers in the salivary glands, resulting in xerostomia and limiting the feasible radiation dosage. The objective of this research project was to develop modified PSMA inhibitors with reduced salivary gland uptake while maintaining high tumor accumulation. To this end, two approaches were investigated: In the first approach, the linker region was optimized through the introduction of charged and uncharged amino acids to improve pharmacokinetic properties. In the second approach, an α-amylase-cleavable linker was developed, enabling selective cleavage of radioactivity in the salivary glands. The project involved the chemical synthesis of modified compounds, their biological characterization, and complete preclinical evaluation. The objective was to identify an optimized compound for more efficient and better tolerated endoradiotherapy of prostate cancer, particularly with actinium-225, an alpha emitter especially suitable for treating resistance or small metastases.
Publications
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Library and post-translational modifications of peptide-based display systems. Biotechnology Advances, 47, 107699.
Dotter, Hanna; Boll, Melanie; Eder, Matthias & Eder, Ann-Christin
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PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives. Cancers, 13(16), 3967.
El Fakiri, Mohamed; Geis, Nicolas M.; Ayada, Nawal; Eder, Matthias & Eder, Ann-Christin
