Pratt Edwin C, Mandleywala Komal, Bauer David, Bolaender Alexander, Chao Grace, Castanares Mark A, Collins Emily C, Lewis Jason S
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eli Lilly and Company, Indianapolis, IN, USA.
Nucl Med Biol. 2025 Jul 15;148-149:109051. doi: 10.1016/j.nucmedbio.2025.109051.
Mesothelin is a membrane bound antigen overexpressed in a wide array of cancers including ovarian, pancreatic, lung, and triple negative breast cancers. Here a full-length IgG antibody developed against mesothelin, called MESO-HSS1 was conjugated for immunoPET imaging and assessed in-vivo in a H956 mesothelin positive model. Furthermore, random lysine conjugation as well as a site selective conjugation method were compared in two pretargeting models for overall tumor uptake alongside non target organs and tumor to organ ratios. Overall, [Zr]Zr-DFO-MESO-HSS1 was found to be a suitable immunoPET radiotracer for the detection of the mesothelin low cancer line H596 as early as 24 h post injection with up to 20.1 % injected dose per gram by 144 h. Furthermore, in pretargeted models, lysine conjugation of TCO-Lys-MESO-HSS1 with [Cu]Cu-Sar-Tz yielded the highest tumor uptake at 2.6 % injected dose per gram at 24 h. Imaging 4 h post injection of [F]F-Al-NOTA-PEG-Tz however was best with TCO-SS-MESO-HSS1 with improved tumor to organ ratios as expected from site selective modifications. High tumor to pancreas ratios suggests mesothelin imaging could be a highly effective diagnostic for pancreatic cancer identification. Together these data show MESO-HSS1 as a direct immunoPET or pretargeting agent as a viable immunoPET system for imaging mesothelin positive cancers.
间皮素是一种膜结合抗原，在包括卵巢癌、胰腺癌、肺癌和三阴性乳腺癌在内的多种癌症中过表达。在此，针对间皮素开发的一种全长IgG抗体，称为MESO-HSS1，被用于免疫正电子发射断层显像（immunoPET）成像，并在H956间皮素阳性模型中进行体内评估。此外，在两个预靶向模型中比较了随机赖氨酸偶联以及位点选择性偶联方法对肿瘤整体摄取以及非靶器官和肿瘤与器官比值的影响。总体而言，发现[Zr]Zr-DFO-MESO-HSS1是一种合适的免疫正电子发射断层显像放射性示踪剂，可在注射后24小时最早检测到间皮素低表达的癌症细胞系H596，到144小时时每克可达注射剂量的20.1%。此外，在预靶向模型中，TCO-Lys-MESO-HSS1与[Cu]Cu-Sar-Tz的赖氨酸偶联在24小时时产生了最高的肿瘤摄取，为每克注射剂量的2.6%。然而，注射[F]F-Al-NOTA-PEG-Tz后4小时成像，TCO-SS-MESO-HSS1效果最佳，肿瘤与器官比值有所改善，这是位点选择性修饰所预期的。高肿瘤与胰腺比值表明间皮素成像可能是识别胰腺癌的一种高效诊断方法。这些数据共同表明MESO-HSS1作为直接免疫正电子发射断层显像剂或预靶向剂，是用于间皮素阳性癌症成像的可行免疫正电子发射断层显像系统。
