THG-009 ([123I]-PARPi) SPECT imaging in the management of oncology patients

Introduction: Poly (ADP-ribose) polymerase-1 (PARP-1) plays a role in cancers by mediating DNA damage repair, transcriptional regulation, and nuclear hormone receptor signaling. THG-009 ([¹²³I]-PARPi) (new radiolabeled PARPi inhibitor) is a novel and highly promising radiotracer for SPECT imaging that reflects active PARP expression. We report on the first in man clinical translation to assess biodistribution and tumor uptake in patients with glioblastoma, head and neck cancer, small cell neuroendocrine lung carcinoma and breast cancer.

Methods: We prospectively evaluated eleven patients (age 44 to 66 years) with histopathologically proven glioblastoma (2), head and neck cancer (2), small cell neuroendocrine lung carcinoma (1) and breast cancers (6). The synthesis of THG-009 was performed as previously reported by Wilson et al. (1). High molar activity and radiochemical purity THG-009 at an activity ranging from 370 to 555 MBq, adjusted for patient weight was injected intravenously for the SPECT/CT scan. All scans were performed 1 h, 4 h and 24 h after injection of THG-009 and the vitals were assessed before and after administration.

Results: The biodistribution analysis revealed high THG-009 avidity in 7 of the 11 patients. THG-009 had focal uptake in all primary lesions (n = 7, L/B = 2.8 ± 1.2) and all PARP positive lymph nodes (n = 4). Focal uptake of tracer in primary and nodal lesions was corroborated by CT alone or in combination with [¹⁸F]FDG. THG-009 was well-tolerated by all eleven patients without any safety concerns.

Conclusions: We present first evidence of diagnostic potential of THG-009 SPECT/CT in patients with Glioblastoma, head and neck cancer and breast cancers. Based on the Auger-electron emitting properties of I-123, THG-009 should be evaluated in larger studies for both diagnostic imaging and, possibly, targeted therapy of malignant tumors with a high content of PARP expression.