Cerenkov luminescence imaging for radiation dose calculation of a 90Y-labeled gastrin-releasing peptide receptor

Christian Lohrmann, Hanwen Zhang, Daniel L.J. Thorek, Pooja Desai, Pat B. Zanzonico, Joseph O'Donoghue, Christopher P. Irwin, Thomas Reiner, Jan Grimm, Wolfgang A. Weber

Research output: Contribution to journalArticlepeer-review

Abstract

90Y has been used to label various new therapeutic radiopharmaceuticals. However, measuring the radiation dose delivered by 90Y is challenging because of the absence of suitable y emissions and its low abundance of positron emissions. For the treatment of prostate cancer, radiolabeled gastrin-releasing peptide receptor (GRPr) antagonists have yielded promising results in mouse models. In this study, we evaluated whether Cerenkov luminescence imaging (CLI) could be used to determine radiation doses of a 90Y-labeled GRPr antagonist in nude mice. Methods: Mice bearing subcutaneous prostate cancer xenografts were injected with 0.74-18.5 MBq of the 90Y-labeled GRPr antagonist DOTA-AR and underwent in vivo and ex vivo CLI at 1-48 h after injection. After imaging, animals were sacrificed, their tumors and organs were harvested, and the activity concentration was measured by liquid scintillation counting. In a second set of experiments, Cerenkov photon counts for tumor and kidney on in vivo CLI were converted to activity concentrations using conversion factors determined from the first set of experiments. Results: 90Y-DOTA-AR concentration in the 3 tumor models ranged from 0.5% to 4.8% of the injected activity per gram at 1 h after injection and decreased to 0.05%-0.15 injected activity per gram by 48 h after injection. A positive correlation was found between tumor activity concentrations and in vivo CLI signal (r2 = 0.94). A similar correlation was found for the renal activity concentration and in vivo Cerenkov luminescence (r2 = 0.98). Other organs were not distinctly visualized on the in vivo images, but ex vivo CLI was also correlated with the radioactivity concentration (r2 = 0.35-0.94). Using the time-activity curves from the second experiment, we calculated radiation doses to tumor and kidney of 0.33 ± 0.12 (range, 0.21-0.66) and 0.06 ± 0.01 (range, 0.05-0.08) Gy/MBq, respectively. Conclusion: CLI is a promising, low-cost modality to measure individual radiation doses of 90Y-labeled compounds non-invasively. The use of Cerenkov imaging is expected to facilitate the development and comparison of 90Y-labeled compounds for targeted radiotherapy.

Original languageEnglish (US)
Pages (from-to)805-811
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Cerenkov luminescence imaging
  • Gastrin-releasing peptide receptor
  • Targeted radiotherapy
  • Y

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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