TWO STEP TC99M IMAGING USING BISPECIFIC ANTIBODIES

制备了一系列抗cea x抗铟- dtpa （hMN-14 x 734）双特异性抗体（bsAbs）并对其进行了表征。比较这些bsab在GW-39荷瘤小鼠体内的肿瘤摄取和清除模式。具有最高肿瘤摄取和高肿瘤/非肿瘤（T/NT）比的bsAb将进一步研究发展成为一种成像系统。肿瘤将被bsAb靶向。待肿瘤有足够时间增生，且T/NT比值较高后，注射99m/Tc-IMP-192。IMP-192是一种肽基tc螯合剂，用过量的铟配制，并冻干成一个小瓶，用Tc-99m进行放射性标记。Imp-192含有两个DTPA分子，用于抗体识别，并迅速从循环中清除。bsAb和Tc-99m标记肽的剂量将被优化用于预靶向成像。通过这种预先定位的方法，期望降低背景。这种优化的预靶向方法随后将适用于使用Re-188或Re-186代替Tc-99m的预靶向放射免疫治疗。Re-188放射性标记需要重新配制肽。拟议的商业应用：最终产品被设想为一种双瓶成像试剂盒，用于诊断各种癌症。第一个小瓶将含有针对肿瘤的双特异性抗体。第二个小瓶将包含冻干肽基Tc-99m螯合剂，用于Tc-99m的即时放射性标记。对于治疗，Tc-99m将转换为Re-1898，肽将重新配制。

A series of anti-CEA x anti-indium-DTPA (hMN-14 x 734) bispecific antibodies (bsAbs) will be prepared and characterized. These bsAbs will be compared for tumor uptake and clearance pattern in GW-39 tumor bearing mice. The bsAb with the highest tumor uptake and high tumor/non-tumor (T/NT) ratio will be studied further to develop into an imaging system. The tumors will be targeted with the bsAb. After allowing a sufficient time for tumor accretion and a high T/NT ratio, 99m/Tc-IMP-192, will be injected. IMP-192, a peptidyl Tc-chelator, is formulated with excess indium and lyophilized into a single vial for radiolabeling with Tc-99m. Imp-192 contains two DTPA molecules for antibody recognition and clears rapidly from circulation. The dose of the bsAb and the Tc-99m labeled peptide will be optimized for pretargeted imaging. Reduced background is expected with this pretargeted approach. This optimized pretargeted approach will then later be applicable to pretargeted radioimmunotherapy using Re-188 or Re-186 instead of Tc-99m. Re-188 radiolabeling will require reformulation of the peptide. PROPOSED COMMERCIAL APPLICATION: Final product is envisaged as a two-vial imaging kit for the diagnosis of a variety of cancers. The first vial will contain the bispecific antibody to target the tumors. The second vial will contain a lyophilized peptidyl Tc-99m chelator for instant radiolabeling with Tc-99m. For therapy, Tc-99m will be switched to Re-1898 and peptide will be reformulated.