Novel Hyperpolarized Agents for Metabolic Imaging of Cancer

 描述(申请人提供)：我们的目标是开发用于超极化13C磁共振波谱(MRS)的分子显像剂，有效地进入恶性肿瘤组织的细胞内环境，并提供对肿瘤代谢谱的洞察。将探索一系列13C标记的三羧酸循环中间体类似物，它们表现出增强的细胞通透性和有效的代谢。通过化学合成，羧酸官能团的系统修饰将产生相应的生物可裂解的羧基部分，并提供具有所需性质的探针。这些药物将被评估以确定理想的候选药物，并随后用于前列腺癌细胞和动物模型中三羧酸循环代谢的超极化13C MRS研究。超极化~(13)C磁共振波谱中分子探针传递的新策略将为靶向肿瘤代谢的特定方面提供独特的机会，这将对药物化学、化学生物学和医学成像具有广泛的重要性。

 DESCRIPTION (provided by applicant): We aim to develop molecular imaging agents for hyperpolarized 13C magnetic resonance spectroscopy (MRS) that effectively access the intracellular environment of malignant tissue and provide insight into the metabolic profile of tumors. A series of 13C-labeled analogs of tricarboxylic cycle intermediates, which exhibit enhanced cell permeability and are effectively metabolized, will be explored. Through chemical synthesis, systematic modification of carboxylic acid functional groups will yield the corresponding biologically cleavable carboxyl moieties and provide probes with the desired properties. These agents will be assessed to determine ideal candidates and subsequently be employed in hyperpolarized 13C MRS studies of tricarboxylic acid cycle metabolism in cellular and animal models of prostate cancer. New strategies for molecular probe delivery in hyperpolarized 13C MR spectroscopy will offer unique opportunities for targeting specific aspects of tumor metabolism, which will be of broad importance to medicinal chemistry, chemical biology, and medical imaging.