Synthesis and in vitro/in vivo evaluation of 99mTc-labeled folate conjugates for folate receptor imaging

被引：39

作者：

Lu, Jie ^{[1
]}

Pang, Yan ^{[1
]}

Xie, Fang ^{[1
]}

Guo, Hongjuan ^{[1
]}

Li, Yan ^{[1
,2
,3
]}

Yang, Zhi ^{[2
,3
]}

Wang, Xuebin ^{[1
]}

机构：

[1] Beijing Normal Univ, Coll Chem, Minist Educ, Key Lab Radiopharmaceut, Beijing 100875, Peoples R China

[2] Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China

[3] Peking Univ, Breast Ctr, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100142, Peoples R China

来源：

NUCLEAR MEDICINE AND BIOLOGY | 2011年 / 38卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Technetium-99m; Folate receptor; Folate conjugate; KB tumor; Biodistribution; PRECLINICAL EVALUATION; BIOLOGICAL EVALUATION; BINDING-PROTEIN; BIODISTRIBUTION; STABILITY; DESIGN; LIGAND; SPECT; F-18;

D O I：

10.1016/j.nucmedbio.2010.11.007

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Introduction: Folate receptor (FR) is a potential molecular target for radionuclide imaging since it is overexpressed in many human epithelial tumor cells. In this study, a novel folate conjugate was synthesized and labeled with Tc-99m using different coligands. In vitro and in vivo evaluations of these complexes have been done to explore the effect of coligands on the stable, affinity and pharmacokinetic properties. Methods: A novel folate conjugate, HYNIC-NHHN-FA, was synthesized and characterized. This conjugate was radiolabeled with Tc-99m using tricine, tricine /diphenylphosphinobenzene-3-sulfonic acid sodium (TPPMS) and tricine /trisodium triphenylphosphine-3,3',3 ''-trisulfonate (TPPTS) as coligands, respectively. The complexes were purified by high-pressure liquid chromatography (HPLC). In vitro and in vivo evaluations were performed with FR-positive KB cells, normal Kunming mice and athymic nude mice bearing KB tumors. Results: Labeling with Tc-99m using different coligands resulted in three complexes, Tc-99m (HYNIC-NHHN-FA)(tricine), 5, Tc-99m (HYNIC-NHHN-FA)(tricine/TPPMS), 6 and Tc-99m (HYNIC-NHHN-FA)(tricine/TPPTS), 7. Complex 5 showed at least two isomers and was unstable after being purified by HPLC. Complexes 6 and 7 displayed high stability and similar affinity to FR in vitro. Biodistribution results in athymic nude mice bearing KB tumor showed that complex 7 had a high uptake in FR-positive tumor (9.79=/-1.66%ID/g at 4 h postinjection), and the results of blockade studies confirmed the specific accumulation of the radiotracer in vivo. However, complex 6 showed a low tumor uptake due to its fast excretion via the gastrointestinal tract. Conclusion: The modification of the coligands can significantly alter the pharmacokinetic properties of the corresponding Tc-99m-HYNIC complexes. Tc-99m (HYNIC-NHHN-FA)(tricine/TPPTS), 7 could be a promising radiotracer for FR imaging. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：557 / 565

页数：9

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