Size-Dependent Uptake of Tc(I)-Labeled RGD Analogs

描述（申请人提供）：抗血管生成治疗是目前癌症研究中最活跃的领域之一。限制血管生成的基本方法有四种：阻断生长因子、抑制基质蛋白酶、直接靶向内皮细胞和上调内源性抑制剂。尽管迄今为止还没有阻断血管生成的简单答案，但目前临床结果中的一种方法是靶向整合素受体（Vitaxin， EMD121974和SB-265123，其靶向α v， β 3整合素）。由于血管生成的关键生化参数尚未确定，并且在不同的肿瘤类型中可能是不同的生化靶点，因此整合素受体的分子探针对于指导患者选择整合素受体拮抗剂治疗具有重要意义。

DESCRIPTION (provided by applicant): Anti-angiogenic therapy is currently one of the most active fields in cancer research. There are four basic approaches to limiting angiogenesis: blocking growth factors, inhibiting matrix proteases, directly targeting endothelial cells, and upregulating endogenous inhibitors. Although there is no simple answer to date for blocking angiogenesis, one approach now in clinical results is targeting integrin receptors (Vitaxin, EMD121974, & SB-265123 which target the alpha v, beta 3 integrin). Since the key biochemical parameter in angiogenesis has not been defined and is likely to be a different biochemical target in different tumor types, a molecular probe for the integrin receptor will be important in guiding the choice of patients for integrin receptor antagonist therapy. Five different molecular weight dextrans will be used to span the spectra of possible permeabilities. One set of dextrans will be labeled with both the RGD peptide and Tc-99m. The other set of dextrans will be labeled with RGE and Tc-99m and will serve as a control because changing the molecular weight of the dextran can result in "localization" that is heavily dependent on the permeability of the molecule rather than the specific binding of the RGD peptide to the integrin receptor. This control molecule will therefore serve as a reference for non-integrin receptor processes much like the "reference tissue" model is used in positron emission tomography (PET) neurochemistry imaging. In that case, a tissue that does not contain the target receptor is used as a reference whereas in this study, the dextran control without the RGD peptide will serve as the reference.