A first-in-human study of [⁶⁸Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death.

Abstract

This study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with ⁶⁸Ga ([⁶⁸Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death. Five participants with at least one extracranial site of solid malignancy > 2 cm and no active cancer treatment in the 8 weeks prior to the study were enrolled. Participants were administered 205 ± 4.1 MBq (range, 200-211 MBq) of [⁶⁸Ga]Ga-CDI and 8 serial PET scans acquired: the first commencing immediately and the last 3 h later. Participants were monitored for clinical, laboratory and electrocardiographic side effects and adverse events. Urine and blood radioactivity was measured. Spherical volumes of interest were drawn over tumour, blood pool and organs to determine biodistribution and calculate dosimetry. In one participant, tumour specimens were analysed for cell death using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. [⁶⁸Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [⁶⁸Ga]Ga-CDI is renally excreted, demonstrates low levels of physiologic uptake in the other organs and has excellent imaging characteristics. The mean effective dose was 2.17E - 02 ± 4.61E - 03 mSv/MBq. It images constitutive tumour cell death and correlates with tumour cell death on histology. [⁶⁸Ga]Ga-CDI is a novel cell death imaging radiopharmaceutical that is safe, has low radiation dosimetry and excellent biodistribution and imaging characteristics. It has potential advantages over previously investigated radiopharmaceuticals for imaging of cell death and has progressed to a proof-of-concept trial. ACTRN12621000641897 (28/5/2021, retrospectively registered).