PT - JOURNAL ARTICLE AU - Das, Bhaskar AU - Mani, Sridhar TI - Design and synthesis 3-Phenyl-2H-benzo[b] [1, 4] Oxazine containing PET imaging agent for hypoxia DP - 2009 May 01 TA - Journal of Nuclear Medicine PG - 1942--1942 VI - 50 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/50/supplement_2/1942.short 4100 - http://jnm.snmjournals.org/content/50/supplement_2/1942.full SO - J Nucl Med2009 May 01; 50 AB - 1942 Objectives The objective in this study to design and synthesize novel PET imaging agent of hypoxia. Hypoxia is a universal hallmark of tumor cells in vivo. Within the tumor micro environment, it contributes towards resistance to radiation and chemotherapy. It is known that hypoxic cells are highly reductive in nature. Bio-reductive activation is a well-established concept for achieving selective toxicity of anti tumor agents to hypoxic cells. Keeping above objective in mind we developed novel small oxazine library to treat hypoxic cell. Methods We synthesized a small library of 3-phenyl-2H-benzo[b] [1, 4] oxazine derivatives and their cytotoxicity activity were tested against hypoxic and normoxic cell. We further derivatized our lead compound to synthesize 18F and 11C labeled PET imaging agent of hypoxia. Results We found compound JA155 specifically inhibit hypoxic cancer cell growth (IC50 10+3.7 mM) while “normoxic” cells (IC50 >1000mM) and compound JA153 inhibits hypoxia cancer cell growth (IC50 100+2.2 mM) and normoxic cells (IC50 >1000mM). The absence of toxicity in normoxic cells is a crucial feature for these compounds and based on this premise, we will be able to lead optimize its potency in hypoxic conditions. Compound JA155 could further derivatized as 11C labeled and JA153 as 18F labeled PET Imaging agents. Conclusions We synthesized a small library of 3-phenyl-2H-benzo[b] [1, 4] oxazine derivatives and their cytotoxicity activity were tested against hypoxic and normoxic cell. Using our lead molecule, we are developing novel hypoxia PET imaging agent will communicate in near future.