TC-99M ADENINE NUCLEOTIDE POLYPHOSPHATE IMAGING AGENTS

发展非侵入性的方法来区分正常组织和肿瘤组织对于理解和治疗癌症至关重要。本应用的目的是利用乳腺肿瘤细胞对完整核苷酸多磷酸盐的优先摄取作为乳腺癌的早期筛查。之前，我们报道了99mTc-Ap4A（二腺苷5',5',P1， p4 -四磷酸）和99mTc-ATP（三磷酸腺苷）在肿瘤中积累。在这里，我们建议利用这些化合物的放射性标记的最新进展和我们的新型99mTc-[coligand]- ap4a复合物在人乳腺肿瘤细胞中的初步生物分布/成像结果，最终目的是开发一种方便的试剂盒配方。我们建议发展放射化学制备和分离一系列新型锝-共聚物-腺嘌呤核苷酸多磷酸复合物的方法，并评估它们作为乳腺肿瘤诊断的特异性示踪剂。放射性标记方法将采用新的配体方法，并研究最近开发的Tc(CO)3+核心，以提高药品生产。拟议的商业应用：成功开发一种技术-共聚物-腺嘌呤核苷酸多磷酸复合物，将使乳腺癌诊断的灵敏度和准确性比目前进行的诊断提高。这种Tc-kit试剂的可用性将增加广泛可用的SPECT成像在乳腺癌诊断和治疗管理中的效用。

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.