Improved Detection of Cancer Using Bi Specific Antibody

描述(逐字摘自申请人的摘要)：诊断成像 癌症已被NCI确定为优先项目，主要原因是 普遍认为，如果癌症能够更准确地定位在 身体，那么病人的管理和可能的结果会有所改善。这 应用将开发一种新的成像模式，即双特异性抗体 (BsMAb)方法，将适用于伽马和PET成像。因为有很多人 正电子发射器的半衰期比伽马发射器短，这种方法 必须能够在同位素注射后的短时间内提供图像。 在此应用中使用的BsMAb方法的初步结果表明 成像可以在I到3个小时内完成。因此，这种方法论应该是 适用于伽马或正电子发射剂。与上级 肿瘤/非肿瘤/肿瘤比值，此方法可提高敏感性和 通过伽马成像或PET(免疫PET)诊断癌症成像的特异性。 该提案包括临床前研究，这些研究将继续建立在 本申请中描述的方法。F(ab‘)2 x Fab’和Fab‘x Fab’BsMAb 将探索构建物以阻止靶向的最佳制剂。 临床研究将在第二年年中提出。临床部 研究将使用人源化抗癌胚抗原(CEA)抗体 (HMN-14)与小鼠抗DTPA-(In)抗体化学偶联形成 BsMAb片段(即Fab‘x Fab’或F(ab‘)2 x Fab’)。临床前研究 已经展示了这种BsMAb靶向方法和一个 氚结合双DTPA多肽可在体内定位结肠癌移植瘤 注射多肽1小时。临床研究将首先检查 使用99mTC-多肽优化该方法的参数 (伽马成像法)。一旦方法学在临床上得到优化， 未来的研究(不包括在本申请中)将开始集中在 更大的患者队列，以使用 99mTc标记的多肽，但我们也建议开始开发一种 使用同样方法的PET成像系统和可能的94TnTc。

DESCRIPTION (Verbatim from the Applicant's Abstract): Diagnostic imaging of cancer has been identified by the NCI as a priority program principally because of the commonly held belief that if cancer can be more accurately located in the body, then patient management and possible outcome will improve. This application will develop a new imaging modality, namely a bispecific antibody (BsMAb) approach that will be suitable for gamma and PET imaging. Since many positron-emitters have a shorter half-life than the gamma-emitters, the method must be able to provide images within a short time after the isotope injection. Preliminary results with the BsMAb approach used in this application indicate imaging will be possible with I to 3 hours. Thus, this methodology should be suitable for either a gamma- or a positron-emitting agent. With superior tumor/non/tumor ratios, this method could improve the sensitivity and specificity of diagnostic cancer imaging by gamma imaging or PET (ImmunoPET). This proposal includes preclinical studies that will continue to build on the methodology described in this application. F(ab')2 x Fab' and Fab' x Fab' BsMAb constructs will be explored to deterrnine the optimal agent for targeting. Clinical studies are proposed by the middle of the second year. The clinical studies will use a humanized anti-carcinoembryonic antigen (CEA) antibody (hMN-14) that is chemically coupled to a murine antiDTPA-(In) antibody to form a BsMAb fragment (i.e., Fab' x Fab' or F(ab')2 x Fab'). Preclinical studies have already shown this BsMAb targeting method together with a technetium-binding di-DTPA peptide can localize colon cancer xenografts within 1 hour of the peptide's injection. Clinical studies will first examine parameters designed to optimize this approach using 99mTc-peptide (gamma-imaging method). Once the methodology has been optimized clinically, future studies (not included in this application) will begin to focus on a larger cohort of patients to test the targeting efficacy using the 99mTc-labeled peptide, but we would also propose to initiate development of a PET imaging system using this same methodology and possibly 94TnTc.