{'fraction_non_alphanumeric': 0.0366364270760642, 'fraction_numerical': 0.0366364270760642, 'mean_word_length': 5.342920353982301, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Abstract 1141: Preclinical analysis of biodistribution and PET imaging of a zirconium-89 labeled PSMA-targeted antibody-chelator conjugate

The PSMA targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) is a targeted alpha therapy approach for metastatic castration resistant prostate cancer that has shown strong anti-tumor activity in PSMA-positive prostate cancer models (Hammer et al. AACR 2017/2018/2019). PSMA-TTC consists of a fully human IgG1 PSMA-targeted antibody covalently linked to a 3,2-HOPO chelator moiety, stably complexing the alpha emitter thorium-227. As this chelator can also complex zirconium-89, positron emission tomography (PET) imaging using the zirconium-89 labeled variant of the PSMA antibody-chelator conjugate could support clinical development of PSMA-TTC by enabling monitoring of organ distribution. Herein, we describe radiolabeling of the PSMA antibody-chelator conjugate with zirconium-89 and its quality control using bioanalytical assays. In addition, the zirconium-89 labeled PSMA antibody-chelator conjugate was injected into mice bearing LNCaP xenograft tumors and biodistribution was assessed by measurement of radioactivity in tumor and organs as well as PET imaging at different time points after injection. The PSMA antibody-chelator conjugate was successfully labeled with zirconium-89 at high yield, purity and specific activity. Target binding was confirmed by determination of the immunoreactive fraction. Biodistribution experiments revealed high, long lasting uptake of zirconium-89 in PSMA-positive LNCaP tumors after single injection of the zirconium-89 labeled conjugate. An uptake of 40-50% of the injected dose per gram of tumor was measured at 24, 48, 72, 168 and 240h after injection. The PET images showed that the zirconium-89 labeled PSMA antibody-chelator conjugate provided an excellent image contrast for the delineation of LNCaP xenografts between 48 and 168 h after administration. Other organs showed only very little background and tumor-to-heart ratio was greater than 10 when PET imaging was performed between 48 and 168 h after injection. These results indicate that the zirconium-89 labeled PSMA antibody-chelator conjugate shows promise for PET imaging studies. These properties may allow its use to support clinical development of PSMA-TTC. Citation Format: Stefanie Hammer, Sabine Zitzmann-Kolbe, Felix Oden, Joerg Jannsen, Eva Bickel, Andre Mueller, Lothar Everz, Urs B. Hagemann, Jenny Karlsson, Olav B. Ryan, Hartwig Hennekes, Patricia E. Cole, Dominik Mumberg. Preclinical analysis of biodistribution and PET imaging of a zirconium-89 labeled PSMA-targeted antibody-chelator conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1141.