(C-91) Comparison of jugular vs. retroorbital intravenous delivery methods of distinct radiotracers in a murine prostate cancer model

Introduction:: Small animal PET-CT is an important imaging tool for preclinical studies, especially those studying cancer. PET-CT imaging involves the administration of radiotracers and the subsequent measurement of their concentrations within regions of interest. Tissue uptake of radiotracers depends highly on the conjugated molecule as well as on mode of administration. Intravenous (IV) administration of radiopharmaceuticals is typically achieved by lateral tail vein injections; however, this method is notoriously difficult to perform, lacks reproducibility, and loses repeatability for multiple injections over time. Direct jugular vein (JV) administration is also an option with very high reproducibility; however, this method requires an invasive microscope-guided surgical procedure to be performed by a skilled researcher and is also limited by repeated injections over time. While some studies have examined the utility of the retroorbital (RO) sinus vein for comparison of tissue-specific radiotracer uptake, there are no studies that comprehensively compare tissue uptake between IV delivery methods of different types of radiopharmaceuticals.

Materials and Methods:: The goal of this study is to compare dynamic pharmacokinetics between JV with RO injections across three different types of radiopharmaceuticals commonly utilized both clinically and preclinically: (1) small molecule (18F-FDG); (2) peptide-based (cRGD2); and (3) nanocarrier (dextran). Each probe will be delivered to autochthonous tumor-bearing transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (n=3/group) at separate weekly imaging sessions, and probe circulation and tissue-specific biodistributions will be measured by dynamic PET-CT scans collected over 30-minute periods.

Results, Conclusions, and Discussions:: Results are in progress, with TRAMP mice currently undergoing weekly ultrasound to monitor tumor growth. Mice are 24 weeks of age, by which time solid tumors will be starting to form. When tumors reach a minimum of 200mm3, mice will be randomized to receive either JV or RO injections of each of the three distinct molecular probes. Baseline dynamic PET-CT imaging results suggest similar tissue biodistributions of each probe following both injection methods, with this study likely concluding that both injection methods yield similar results, as hypothesized. These results are advantageous, as they will enable researchers to perform a much more rapid, efficient, and less invasive RO injection in lieu of other, more challenging or invasive methods of IV radiotracer administration. Results from this study will directly compare the dynamic pharmacokinetics of three commonly utilized diagnostic and, potentially, theranostic probes in an autochthonous mouse model of prostate cancer. Additionally, this study will help inform researchers to design preclinical PET-CT experiments to practice the three R’s of animal research: replacement, reduction, and refinement.


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