First-in-Human Safety, Imaging, and Dosimetry of a Carbonic Anhydrase IX–Targeting Peptide, [ 68 Ga]Ga-DPI-4452, in Patients with Clear Cell Renal Cell Carcinoma
2024; Society of Nuclear Medicine and Molecular Imaging; Volume: 65; Issue: 5 Linguagem: Inglês
10.2967/jnumed.123.267175
ISSN1535-5667
AutoresMichael S. Hofman, Ben Tran, Darren R. Feldman, Anna Pokorska-Bocci, Solen Pichereau, Jonathan Wessen, Mohammad B. Haskali, Richard Sparks, Olena Vlasyuk, Ivana Galetić,
Tópico(s)Peptidase Inhibition and Analysis
Resumo[ 68 Ga]Ga-DPI-4452, a first-in-class carbonic anhydrase IX–binding radiolabeled peptide, is the imaging agent of a theranostic pair with [ 177 Lu]Lu-DPI-4452, developed for selecting and treating patients with carbonic anhydrase IX–expressing tumors. Here, [ 68 Ga]Ga-DPI-4452 imaging characteristics, dosimetry, pharmacokinetics, and safety were assessed in 3 patients with clear cell renal cell carcinoma. Methods: After [ 68 Ga]Ga-DPI-4452 administration, patients underwent serial full-body PET/CT imaging. Blood and urine were sampled. Safety was monitored for 7 d after injection. Results: Tumor uptake was observed at all time points (15 min to 4 h). Across 36 lesions, the SUV max at 1 h after administration ranged from 6.8 to 211.6 (mean, 64.6 [SD, 54.8]). The kidneys, liver, and bone marrow demonstrated low activity. [ 68 Ga]Ga-DPI-4452 was rapidly eliminated from blood and urine. No clinically significant toxicity was observed. Conclusion: [ 68 Ga]Ga-DPI-4452 showed exceptional tumor uptake in patients with clear cell renal cell carcinoma, with very high tumor-to-background ratios and no significant adverse events, suggesting potential diagnostic and patient selection applications.
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