Abstract #5019: Imaging tumor xenografts using retinoid acid derivatives
Authors: Jin Sun, Wei Wang, Arlin Cameron, Michel Mawad, Ho-Young Lee, Shi Ke
Journal: Cancer Research (2009)

Retinoids are natural and synthetic vitamin A derivatives that regulate a multitude of biological processes in mammalian cells. Those include metabolism, development, cell proliferation, differentiation, and carcinogenesis. Retinoids have been used to prevent diseases and tumor formation, include the head and neck, lung, esophagus, and bladder cancers. It also shows the effects of reverse oral premalignancy and significantly decreases second primary tumors. Retinoids treatments benefit those smoking-related second primary tumors in the small size, short-time, well selected patient population. However, the anti-cancer effects of retinoids are poorly understood. The purpose of our study was to develop imaginable retinoid agents and help understanding retinoids actions in the in vitro and in vivo studies. The retinoid acid agents were synthesized and labeled with reporters. The binding of synthetic retinoids were tested in the human tumor cells. The intracellular trafficking of the agents and distribution were imaged by confocal microscope. The whole body distribution and biological dose of those retinoids were determined by molecular imaging modalities. Cell binding studies demonstrated those agents bound to the human tumor cells. Confocal images revealed those agents internalized into the cells. PET imaging showed the tumor has high metabolic status of 18F-FDG. Optical whole images showed the high signal intensity from tumor and liver region. The highest tumor-to-muscle ratio was reached at 7 days after a single injection of 0.7 mg per kilogram of bodyweight per week. Dynamic imaging showed the agents gradually re-distributed to the tumor from the liver. The increase of tumor-to-muscle ratio was correlated to the decrease of liver-to-tumor ratio. Furthermore, our data demonstrated that increasing injection dose from 2.5 to 10 nmol cannot significantly increase tumor-to-muscle ratio (P>0.527); which suggests that high dose is not necessary when the tumor receptors have been saturated at lower therapeutic dose. In conclusion, we demonstrate our synthetic imaginable retinoids can be used for in vitro and in vivo studies. These labeled retinoids could also be used to evaluate the retinoid receptor status in pre-clinical researches. We can use noninvasive molecular imaging modalities to determine the biodistribution of the retinoids in different organs or tissues. We can also quantify the uptakes and correlate them with the disease-response. The imaginable retinoids will allow us to further develop image-guided therapy that using biological dose rather than maximum tolerant doses. We can use imaging method to select target-positive diseases, define the dosage and frequency of administration; as well as following the agents\#8217; traffic in the body. Those agents have potential to detect retinoid receptor positive tumors and/or diseases. JS*, WW*, These authors contributed equally to this work.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5019.