Abstract
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Objectives A variety of NIR cancer targeting agents have been developed for image guided surgery. CLR1502, a phospholipid ether with a NIR beacon, is a novel optical agent that is selectively taken up and retained by a broad spectrum of malignant cancer cells. Determining the relationship of CLR1502 dose to tumor-to-background ratio (TBR) is critical for future preclinical studies and may be the basis for clinical studies. Our primary objective was to determine the relationship between dose of CLR1502 and TBR both in vivo and ex vivo. Our secondary objective was to compare the TBR of two NIR modalities: IVIS Spectrum (Perkin Elmer) and Fluobeam (Fluoptics).
Methods Nine NUDE mice were inoculated with 1x106 PC3 cells and injected with 0.3mg/kg (LOW), 1.2mg/kg (MED), or 3mg/kg (HIGH) of CLR1502. All mice were scanned 5min, 24hr, 48hr, 72hr, and 96hr post-injection with the IVIS and Fluobeam. Tumor and background regions of interest (ROI) were drawn and in vivo TBR was determined for both modalities. After 96hr, the heart, liver, spleen, kidneys, muscle, blood, and tumor were excised, weighed, and scanned ex vivo with the IVIS. ROIs were drawn and average signal per mass was compared among dose groups. The ex vivo tumor to normal organ ratio (TNOR) was determined.
Results In vivo (IVIS) TBR (mean ± SEM) at 96hr for LOW, MED, and HIGH was 1.42 ± 0.13, 1.30 ± 0.07, and 1.10 ± 0.10, respectively. The in vivo (Fluobeam) TBR at 96hr for LOW, MED, and HIGH was 2.02 ± 0.33, 2.22 ± 0.12, and 2.10 ± 0.15, respectively. The ex vivo TNOR are shown in the supplemental table.
Conclusions Our preliminary data suggest that in vivo CLR1502 TBR may be inversely proportional to dose; however, ex vivo TNOR is clearly proportional to dose. In addition, TBR is modality dependent and warrants further investigation. Moreover, ex vivo TNOR is less susceptible to deleterious effects of non-specific uptake than in vivo optical imaging.