Cerenkov luminescence imaging for radiation dose estimation of a 90Y-labeled GRPr antagonist

Objectives 90Y has been used to label various new therapeutic radiopharmaceuticals. However, it is challenging to measure the radiation dose delivered by 90Y because of the absence of suitable gamma emissions. In this study, we evaluated if Cerenkov luminescence imaging (CLI) can be used to determine radiation doses in mice.

Methods Mice bearing subcutaneous PC3, LNCaP or VCaP xenografts were injected with 20-500 µCi of the 90Y labeled GRPr (bombesin) antagonist PETASIN. Animals underwent in-vivo CLI with an IVIS scanner for 5 min at 1-48 h p.i.. After the scan animals were sacrificed, tumor and organs harvested, dissolved and the radioactivity measured in a beta-counter. In a second experiment, tumor bearing mice underwent in-vivo CLI at 4, 24, 48 and 72 h p.i.. Photon counts for tumor and kidney were converted to activity concentrations using calibration factors determined from the first set of experiments.

Results 90Y-PETASIN concentration in the three tumor models ranged from 4.8-2.5 %ID/g at 1 h p.i. and decreased to 0.15-0.05 %ID/g at 48 h p.i.. A close correlation was found between tumor radioactivity concentrations and in-vivo CLI (r2=0.94, slope= 2.9x10-5 (%ID/g)/(p/s/cm2/sr). A similar correlation was found for the renal activity concentration and Cerenkov luminescence (r2=0.98, slope= 2.4x10-5 (%ID/g)/(p/s/cm2/sr). Using the individual time-activity curves from experiment 2 we calculated radiation doses to tumor and kidney of 22.7±7.16 (range 13.4-34.6) Gy/mCi and 5.14 ± 2.52 (range 2.79-9.53) Gy/mCi respectively.

Conclusions Cerenkov luminescence imaging is a promising, low-cost modality to measure individual radiation doses by 90Y labeled peptides for tumor xenografts and kidneys in mice. The use of Cerenkov imaging is expected to facilitate the development and comparison of peptides for targeted radiotherapy.