64Cu-labeled minibody D2101 visualizes CDH17-positive gastric cancer xenografts with short waiting time.

Autor:	Fujiwara K; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba., Akiba H; Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka.; School of Engineering., Tsuji AB; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba., Sudo H; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba., Sugyo A; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba., Nagatsu K; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba., Zhang MR; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba., Iwanari H; Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo., Kusano-Arai O; Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo., Kudo S; School of Engineering., Kikuchi C; School of Engineering., Tsumoto K; Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka.; School of Engineering., Momose T; Department of Radiology, Faculty of Medicine, International University of Health and Welfare, Chiba., Hamakubo T; Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo.; Department of Protein-Protein Interaction Research, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan., Higashi T; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Chiba.
Jazyk:	angličtina
Zdroj:	Nuclear medicine communications [Nucl Med Commun] 2020 Jul; Vol. 41 (7), pp. 688-695.
DOI:	10.1097/MNM.0000000000001203
Abstrakt:	Objective: We previously reported In-labeled anti-cadherin17 (CDH17) IgG visualized CDH17-positive gastric cancer xenografts. Unfortunately, a long waiting time was required to obtain high-contrast images due to long blood retention (blood half-life: 26 h). To accelerate blood clearance, we have developed anti-CDH17 minibody (D2101 minibody) and evaluated the pharmacokinetics in gastric cancer mouse models. Methods: Two different single chain Fvs (scFvs), D2101 mutant and D2111, were developed from each parental IgG. The binding ability to CDH17 and stability in plasma were evaluated. D2101 minibody, constructed based on D2101 mutant scFv, was labeled with Cu (Cu-D2101 minibody), and the in-vitro and in-vivo properties were evaluated by cell ELISA, biodistribution experiments, and PET imaging in mice bearing CDH17-positive AGS and CDH17-negative MKN74 tumors. Results: D2101 mutant and D2111 scFvs showed similar affinities to CDH17. D2101 mutant scFv was more stable than D2111 scFv in plasma. No loss of binding affinity of the D2101 minibody by chelate conjugation and radiolabeling procedures was observed. The biodistribution of Cu-D2101 minibody showed high uptake in AGS tumors and low uptake in MKN74. The blood half-life of Cu-D2101 minibody was 6.5 h. Improved blood clearance of Cu-D2101 minibody provided high tumor-to-blood ratios compared with the previous results of parental IgG in AGS xenograft mice. PET studies showed consistent results with biodistribution studies. Conclusions: Cu-D2101 minibody exhibited higher tumor-to-blood ratios at earlier time points than those of the radiolabeled parental IgG. Cu-D2101 minibody has potential as an immunoimaging agent for CDH17-positive tumors.
Databáze:	MEDLINE
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