|Synthesis and in vitro/in vivo evaluation of Tc-99m-labeled folate conjugates for folate receptor imaging|
|Lu, Jie1; Pang, Yan1; Xie, Fang1; Guo, Hongjuan1; Li, Yan1,2,3; Yang, Zhi2,3; Wang, Xuebin1|
|关键词||Technetium-99m Folate receptor Folate conjugate KB tumor Biodistribution|
|刊名||NUCLEAR MEDICINE AND BIOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Radiology, Nuclear Medicine & Medical Imaging|
|研究领域[WOS]||Radiology, Nuclear Medicine & Medical Imaging|
|关键词[WOS]||PRECLINICAL EVALUATION ; BIOLOGICAL EVALUATION ; BINDING-PROTEIN ; OVARIAN-CANCER ; CELL-LINES ; IN-VIVO ; ACID ; BIODISTRIBUTION ; TISSUES ; STABILITY|
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.
|资助机构||National Natural Science Foundation of China|
|作者单位||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
|Lu, Jie,Pang, Yan,Xie, Fang,et al. Synthesis and in vitro/in vivo evaluation of Tc-99m-labeled folate conjugates for folate receptor imaging[J]. NUCLEAR MEDICINE AND BIOLOGY,2011,38(4):557-565.|
|APA||Lu, Jie.,Pang, Yan.,Xie, Fang.,Guo, Hongjuan.,Li, Yan.,...&Wang, Xuebin.(2011).Synthesis and in vitro/in vivo evaluation of Tc-99m-labeled folate conjugates for folate receptor imaging.NUCLEAR MEDICINE AND BIOLOGY,38(4),557-565.|
|MLA||Lu, Jie,et al."Synthesis and in vitro/in vivo evaluation of Tc-99m-labeled folate conjugates for folate receptor imaging".NUCLEAR MEDICINE AND BIOLOGY 38.4(2011):557-565.|