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 Journal Article
| Authors: | Hofman, M. S.; Tran, B.; Feldman, D. R.; Pokorska-Bocci, A.; Pichereau, S.; Wessen, J.; Haskali, M. B.; Sparks, R. B.; Vlasyuk, O.; Galetic, I. |
| Article Title: | 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 |
| Abstract: | [68]Ga-DPI-4452, a first-in-class carbonic anhydrase IX-binding radiolabeled peptide, is the imaging agent of a theranostic pair with [177Lu]Lu-DPI-4452, developed for selecting and treating patients with carbonic anhydrase IX-expressing tumors. Here, [68]Ga-DPI-4452 imaging characteristics, dosimetry, pharmacokinetics, and safety were assessed in 3 patients with clear cell renal cell carcinoma. Methods: After [68]Ga-DPI-4452 administration, patients underwent serial fullbody 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 (15min to 4h). Across 36 lesions, the SUVmax at 1h 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-DPI- 4452was rapidly eliminated fromblood and urine.No clinically significant toxicity was observed. Conclusion: [68]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. © 2024 by the Society of Nuclear Medicine andMolecular Imaging. |
| Keywords: | adult; human tissue; middle aged; unclassified drug; drug tolerability; drug safety; patient selection; cancer patient; protein tyrosine kinase inhibitor; injection; carbonate dehydratase ix; isotope labeling; blood sampling; diagnostic value; dosimetry; multicenter study; single drug dose; open study; drug monitoring; drug absorption; drug tumor level; gallium 68; pet/ct; drug elimination; clear cell renal cell carcinoma; maximum standardized uptake value; lutetium 177; immune checkpoint inhibitor; tetraxetan; human; article; positron emission tomography-computed tomography; theranostic; kidney tissue; liver tissue; urine sampling; [<sup>68</sup>ga]ga-dpi-4452; dpi 4452; tetraxetan ga 68 |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 65 |
| Issue: | 5 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2024-05-01 |
| Start Page: | 741 |
| End Page: | 743 |
| Language: | English |
| DOI: | 10.2967/jnumed.123.267175 |
| PUBMED: | 38388517 |
| PROVIDER: | scopus |
| PMCID: | PMC11064824 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
