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

描述（由申请人提供）：抗血管生成治疗是目前癌症研究中最活跃的领域之一。有四种基本方法来限制血管生成：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。尽管迄今为止对于阻断血管生成没有简单的答案，但目前临床结果中的一种方法是靶向整联蛋白受体（Vitaxin、EMD 121974和SB-265123，其靶向α v、β 3整联蛋白）。由于血管生成中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标，因此整合素受体的分子探针在指导患者选择整合素受体拮抗剂治疗方面将是重要的。 将使用五种不同分子量的葡聚糖来跨越可能的渗透性的光谱。一组葡聚糖将用RGD肽和Tc-99 m标记。另一组葡聚糖将用RGE和Tc-99 m标记，并将用作对照，因为改变葡聚糖的分子量可导致“定位”，其严重依赖于分子的渗透性，而不是RGD肽与整联蛋白受体的特异性结合。因此，该对照分子将用作非整联蛋白受体过程的参考，非常类似于正电子发射断层扫描（PET）神经化学成像中使用的“参考组织”模型。在这种情况下，不含靶受体的组织用作参考，而在本研究中，不含RGD肽的葡聚糖对照将用作参考。

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.