title: An imageable retinoid acid derivative to detect human cancer xenografts and study therapeutic dosing to reduce its toxicity.
abstract: Developing agents with 'seek, treat and see' capability is critical for personalized molecular medicine. Those agents will specifically target the disease markers for diagnosis and apply the biologically effective dose for treatment. Retinoids regulate a multitude of biological processes. In addition, retinoic acid can reverse premalignancy, significantly decrease second primary tumors and provide a treatment benefit in head and neck, lung, esophagus, colon and bladder cancer. These data suggest that cancer cells can take up retinoids. Therefore, retinoids are potential tumor-imaging agents. We developed near-infrared (NIR)-labeled retinoid agents to detect human cancers, visualize drug redistribution within the body, determine the optimal biological dose and reduce systemic toxicity. Our data demonstrate that the retinoid agent, but not the free dye, binds to the human tumor cells and is internalized, where it permits the imaging of human cancer xenografts. The high dose of retinoid agent is significantly associated with systemic toxicity. In summary, synthetic NIR-labeled retinoid agents can be used to detect multiple human cancer xenografts as the agent is internalized by cancer cells. The binding of the agent to the tumor xenografts is dependent on the redistribution of the agent. Therapeutic agents labeled with reporters will interrogate tumor-drug interactions and permit analysis of biodistribution, pharmacokinetics and pharmacodynamics in real time. At the same time, we can apply the biologically effective dose for therapy, instead of the traditional maximum tolerated dose, to reduce systemic toxicity.
authors.affiliation: Department of Radiology, Baylor College of Medicine, One Baylor Plaza, MS 360, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Arlin G
authors.initials: AG
authors.lastname: Cameron
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Wendt
authors.forename: Michel E
authors.initials: ME
authors.lastname: Mawad
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009132:Muscles / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*; D013696:Temperature; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014212:Tretinoin / Q000031:analogs & derivatives*
chemical_list: D014212:Tretinoin