title: Cerenkov Luminescence Imaging for Radiation Dose Calculation of a ⁹⁰Y-Labeled Gastrin-Releasing Peptide Receptor Antagonist.
abstract: (90)Y has been used to label various new therapeutic radiopharmaceuticals. However, measuring the radiation dose delivered by (90)Y is challenging because of the absence of suitable γ 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 (90)Y-labeled GRPr antagonist in nude mice.
  
  
  METHODS
  Mice bearing subcutaneous prostate cancer xenografts were injected with 0.74-18.5 MBq of the (90)Y-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
  (90)Y-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 (r(2) = 0.94). A similar correlation was found for the renal activity concentration and in vivo Cerenkov luminescence (r(2) = 0.98). Other organs were not distinctly visualized on the in vivo images, but ex vivo CLI was also correlated with the radioactivity concentration (r(2) = 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.
  
  
  CONCLUSIONS
  CLI is a promising, low-cost modality to measure individual radiation doses of (90)Y-labeled compounds noninvasively. The use of Cerenkov imaging is expected to facilitate the development and comparison of (90)Y-labeled compounds for targeted radiotherapy.
authors.affiliation: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York lohrmanl@mskcc.org.
authors.forename: Christian
authors.initials: C
authors.lastname: Lohrmann
authors.affiliation: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medicine, Baltimore, Maryland.
authors.forename: Daniel L J
authors.initials: DL
authors.lastname: Thorek
authors.affiliation: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Pooja
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Donoghue
authors.affiliation: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Irwin
authors.affiliation: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
authors.affiliation: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jan
authors.initials: J
authors.lastname: Grimm
authors.affiliation: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D049449:Luminescence; D008297:Male; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology; D011829:Radiation Dosage; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*
chemical_list: D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D018004:Receptors, Bombesin; C113625:yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid
keywords: 90Y; Cerenkov luminescence imaging; gastrin-releasing peptide receptor; targeted radiotherapy
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