Improved Detection of Cancer Using Bi Specific Antibody

描述（逐字摘自申请人摘要）：诊断成像 癌症被NCI确定为优先计划，主要是因为 人们普遍认为，如果癌症可以更准确地定位在 身体，然后病人的管理和可能的结果将得到改善。这 该应用将开发一种新的成像模式，即双特异性抗体， （BsMAb）方法，其将适用于伽马和PET成像。由于许多 正电子发射体具有比γ发射体更短的半衰期， 必须能够在同位素注入后的短时间内提供图像。 本申请中使用的BsMAb方法的初步结果表明， 成像将在1至3小时内成为可能。因此，该方法应 适合于γ-或正电子发射剂。与上级 肿瘤/非肿瘤/肿瘤比值，该方法可以提高灵敏度， 通过伽马成像或PET（ImmunoPET）诊断癌症成像的特异性。 该提案包括临床前研究，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 将探索构建体以确定用于靶向的最佳试剂。 第二年中期提出临床研究。临床 研究将使用人源化的抗癌胚抗原（CEA）抗体 （hMN-14），其与鼠抗DTPA-（In）抗体化学偶联以形成 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， 锝结合二-DTPA肽可以定位结肠癌异种移植物内 注射肽1小时。临床研究将首先检查 设计参数以使用99 mTc-肽优化该方法 （伽马成像方法）。一旦该方法在临床上得到优化， 未来的研究（不包括在本申请中）将开始关注 更大的患者队列，以使用 99 mTc标记的肽，但我们也建议开始开发一种 PET成像系统使用相同的方法和可能的94 TnTc。

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.