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Radiolabeled Anti-Adenosine Triphosphate Synthase Monoclonal Antibody as a Theragnostic Agent Targeting Angiogenesis

Authors
Park, BN; Lee, SJ; Roh, JH; Lee, KH; An, YS; Yoon, JK
Citation
Molecular imaging, 16:1536012117737399-1536012117737399, 2017
Journal Title
Molecular imaging
ISSN
1535-35081536-0121
Abstract
INTRODUCTION: The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated.
METHODS: Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of (125)I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3). For radioimmunotherapy, 18.5 MBq (131)I-ATPS mAb (n = 7), isotype immunoglobulin G (IgG) (n = 6), and vehicle (n = 6) were injected into MKN-45 tumor-bearing mice for 4 weeks, and tumor volume and percentage of tumor growth inhibition (TGI) were compared each week.
RESULTS: MKN-45 cells showed the highest in vitro cellular binding after 4 hours (0.00324 +/- 0.00013%/mug), which was significantly inhibited by unlabeled ATPS mAb at concentrations of greater than 0.4 muM. The in vitro retention rate of (125)I-ATPS mAb in MKN-45 cells was 64.1% +/- 1.0% at 60 minutes. The highest tumor uptake of (125)I-ATPS mAb in MKN-45 tumor-bearing mice was achieved 24 hours after injection (6.26% +/- 0.47% injected dose [ID]/g), whereas tumor to muscle and tumor to blood ratios peaked at 48 hours. The 24-hour tumor uptake decreased to 3.43% +/- 0.85% ID/g by blocking with unlabeled ATPS mAb. After 4 weeks of treatment, mice receiving (131)I-ATPS mAb had significantly smaller tumors (679.4 +/- 232.3 mm(3)) compared with control (1687.6 +/- 420.4 mm(3), P = .0431) and IgG-treated mice (2870.2 +/- 484.1 mm(3), P = .0010). The percentage of TGI of (131)I-ATPS mAb was greater than 50% during the entire study period (range: 53.7%-75.9%).
CONCLUSION: The specific binding and antitumor effects of radioiodinated ATPS mAb were confirmed in in vitro and in vivo models of stomach cancer.
Keywords
Adenosine triphosphate synthaseAngiogenesisIodine radioisotopesMonoclonal antibodyRadioimmunotherapy
DOI
10.1177/1536012117737399
PMID
29239276
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Nuclear Medicine & Molecular Imaging
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박, 복남이, 수진안, 영실윤, 준기
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