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. 2024 Feb 22;65(5):740-743.
doi: 10.2967/jnumed.123.267175. Online ahead of print.

First-in-Human Safety, Imaging, and Dosimetry of a Carbonic Anhydrase IX-Targeting Peptide, [68Ga]Ga-DPI-4452, in Patients with Clear Cell Renal Cell Carcinoma

Michael S Hofman  1   2 , Ben Tran  3   2 , Darren R Feldman  4 , Anna Pokorska-Bocci  5 , Solen Pichereau  5 , Jonathan Wessen  5 , Mohammad B Haskali  3   2 , Richard B Sparks  6 , Olena Vlasyuk  5 , Ivana Galetic  4
Affiliations

First-in-Human Safety, Imaging, and Dosimetry of a Carbonic Anhydrase IX-Targeting Peptide, [68Ga]Ga-DPI-4452, in Patients with Clear Cell Renal Cell Carcinoma

Michael S Hofman et al. J Nucl Med. .

Abstract

[68Ga]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, [68Ga]Ga-DPI-4452 imaging characteristics, dosimetry, pharmacokinetics, and safety were assessed in 3 patients with clear cell renal cell carcinoma. Methods: After [68Ga]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 SUVmax 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. [68Ga]Ga-DPI-4452 was rapidly eliminated from blood and urine. No clinically significant toxicity was observed. Conclusion: [68Ga]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.

Keywords: PET/CT; [68Ga]Ga-DPI-4452; clear cell renal cell carcinoma; theranostic.

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Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
Whole-body maximum-intensity projections over time after [68Ga]Ga-DPI-4452 administration. (A) Representative PET images at 4 postadministration time points. (B) PET/CT image at 1 h to allow visualization of anatomic contour.
FIGURE 2.
FIGURE 2.
Whole-body maximum-intensity PET projections from 3 patients with ccRCC 1 h after administration of [68Ga]Ga-DPI-4452. High tumor-to-background contrast is seen, with background physiologic uptake in stomach, small bowel, and bladder. Partially transparent maximum-intensity projections of corresponding CT scans are overlaid on PET images to allow visualization of anatomic contour.
FIGURE 3.
FIGURE 3.
Representative images from patient with ccRCC 1-h after [68Ga]Ga-DPI-445 administration. (A) Transaxial PET images (top), fused PET/CT images (middle), and CT images (bottom) showing tracer uptake in tumors (arrows) in parotid gland, upper thoracic vertebra, and chest wall (left to right). (B) Anterior maximum-intensity projection of whole-body image.
FIGURE 4.
FIGURE 4.
Organ-absorbed doses of [68Ga]Ga-DPI-4452 in 3 patients with ccRCC. Error bars represent SD.
See this image and copyright information in PMC

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References

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