TC-99M ADENINE NUCLEOTIDE POLYPHOSPHATE IMAGING AGENTS

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The development of non-invasive methodologies to differentiate between normal and neoplastic tissue is crucial to the understanding and treatment of cancer. The purpose of this application is to utilize the preferential uptake of intact nucleotide polyphosphates in breast tumor cells as an early screening for breast cancer. Previously, we reported that 99mTc-Ap4A (diadenosine 5', 5", P1, P4-tetraphosphate and 99mTc-ATP (adenosine triphosphate) accumulate in tumors. Here we propose to capitalize on recent progress in the radiolabeling of these compounds and preliminary biodistribution / imaging results of our novel 99mTc-[coligand]-Ap4A complex in human breast tumor cells with the ultimate aim of developing a convenient kit formulation. We propose to develop methods for radiochemical preparation and isolation of a series of novel technetium- coligand-adenine nucleotide polyphosphate complexes and evaluate them as specific tracers for breast tumor diagnosis. The radiolabeling methodology will employ new coligand approaches, as well as investigate the recently developed Tc(CO)3+ core for enhanced pharmaceutical production. PROPOSED COMMERCIAL APPLICATIONS: Successful development of a technetium-coligand-adenine nucleotide polyphosphate complex will allow for improved sensitivity and accuracy of breast cancer diagnosis over those currently performed. The availability of such a Tc-kit agent will increase the utility of widely available SPECT imaging for the diagnosis and the therapeutic management of breast cancer.