First-in-human phase 0 safety, imaging, pharmacokinetics, and dosimetry study of ⁶⁴ Cu-PD-32766, a carbonic anhydrase IX (CAIX)-targeting peptide, in patients with clear cell renal cell carcinoma (ccRCC).

TPS605 Background: Carbonic Anhydrase (CA)IX is a type of carbonic anhydrase and is expected to be a useful target for detecting tumors with poor prognosis. Particularly in clear cell renal cell carcinoma, high CAIX expression has been reported in a large proportion of patients. In this study, we developed a novel radioligand agent called PD-32766 that specifically binds to CAIX and administered it to recurrent cases of clear cell renal cell carcinoma (ccRCC) patient. Safety, imaging, pharmacokinetics and dosimetry are evaluated. Methods: Between May 2024 and September 2024, PD-32766 labeled by positron-emitting 64Cu (64Cu-PD-32766) was intravenously administered at a dose of 148 MBq (±20%) to five patients with clear cell renal cell carcinoma who had either distant metastasis or local recurrence, and who met other eligibility criteria. PET/CT imaging was performed at 5, 60, 120, 240 minutes, 24, and 48 hours after administration, with vital signs, blood tests, and urinalysis performed as needed. The primary endpoint was the patient-level PET uptake positivity rate of target tumor regions. Secondary endpoints included the number of positive lesions, pharmacokinetics, estimated radiation dose, and the frequency and types of adverse events. This trial is registered under the jRCT trial identifier:jRCTs031240046. Results: 64Cu-PD-32766 demonstrated good tolerability, with no serious complications observed. The average patient-level PET uptake positivity rate at 120 minutes was 75%. The average lesion-level PET positivity rate was 96.2%. Tumor uptake was highest at 60, 120 minutes post-administration. The effective dose for whole body was 0.102±0.036 mSv/MBq. The stomach and small intestine had the highest absorbed doses among all organs, with 0.712±0.287 mGy/MBq and 0.304±0.067 mGy/MBq, respectively. Conclusions: 64Cu-PD-32766 demonstrated an excellent positivity rate in ccRCC patients with no significant adverse events and tolerated radiation dose to normal organs, proving high diagnostic capability and suggesting future therapeutic uses by labeling with therapeutic radionuclides. Clinical trial information: jRCTs031240046 .