铜-67标记的卟啉及卟啉-A6H免疫缀合物的制备与生物分布

Preparation and biodistribution of copper-67-labeled porphyrins and porphyrin-A6H immunoconjugates.

作者信息

Bhalgat M K, Roberts J C, Mercer-Smith J A, Knotts B D, Vessella R L, Lavallee D K

机构信息

Department of Medicinal Chemistry, University of Utah, Salt Lake City 84112, USA.

出版信息

Nucl Med Biol. 1997 Feb;24(2):179-85. doi: 10.1016/s0969-8051(96)00215-6.

DOI:10.1016/s0969-8051(96)00215-6

PMID:9089710

Abstract

The synthetic porphyrins, N-benzyl-5,10,15,20-tetrakis (4-carboxyphenyl) porphine (N-bzHTCPP) and N-4-nitrobenzyl-5-(4-carboxyphenyl)-10,15,20-tris(4-sulfophenyl) porphine (N-bzHCS3P), represent excellent radiocopper chelating agents that may find utility in antibody-mediated diagnosis and/or therapy. N-bzHCS3P was conjugated to an anti-renal cell carcinoma (RCC) antibody, A6H, and labeled with copper-67. 67CuCS3P-A6H was studied for its biodistribution in human RCC xenograft-bearing nude mice, along with the radiolabeled free porphyrins. The porphyrins resulted in tumor:blood ratios in the range of 3 to 4 after 48 h. The radiolabeled antibody achieved a tumor:blood ratio of over 16 after 45 h, indicating accumulation at the desired site. However, unwanted localization also occurred in the liver and spleen, which will have to be rectified before realizing the full potential of this approach.

摘要

合成卟啉N-苄基-5,10,15,20-四（4-羧基苯基）卟吩（N-bzHTCPP）和N-4-硝基苄基-5-（4-羧基苯基）-10,15,20-三（4-磺基苯基）卟吩（N-bzHCS3P）是优异的放射性铜螯合剂，可能在抗体介导的诊断和/或治疗中有用。N-bzHCS3P与抗肾细胞癌（RCC）抗体A6H偶联，并用铜-67标记。研究了67CuCS3P-A6H在荷人RCC异种移植瘤裸鼠中的生物分布，以及放射性标记的游离卟啉。48小时后，卟啉的肿瘤与血液比值在3至4之间。放射性标记的抗体在45小时后肿瘤与血液比值超过16，表明在所需部位有积聚。然而，肝脏和脾脏中也出现了不必要的定位，在充分发挥这种方法的潜力之前，必须加以纠正。