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Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma.
Bioconjug Chem. 2020 Jul 15; 31(7):1750-1755.BC

Abstract

Single chain antibody fragment (scFv) is a promising agent for imaging and targeted therapy. The objective of the study is to evaluate a kit formulation for 99mTc labeling of scFv for tumor imaging. The scFv was engineered to contain a cysteine tag to accommodate the specific conjugation of HYNIC and subsequent 99mTc labeling. The labeling conditions were formulated to allow instantaneous one-pot quantitative labeling. The reproducibility of labeling was evaluated at various time points during kit storage at -20 °C. In vitro cell binding experiments and HPLC analysis were performed to assess binding affinity and radiolabel stability, respectively. In vivo tumor targeting study was performed in xenograft models with biodistribution studied at 1, 3, and 24 h post-injection. The optimized kit with 5 μg SnF2, pH 5.5, and 50 μg GH along with as low as 15 μg of HYNIC-cys-scFv provided high labeling yield (>95%), high specific activity (1.8 × 107 Ci/Mol), and robust reproducibility with shelf life up to 90 days when stored at -20 °C. The in vitro cell binding study showed the labeled scFv maintained the binding capability with an apparent KD of ∼27 nM. The animal study using tumor-bearing mice showed high tumor uptake at 16.9%ID/g 24 h post-injection along with rapid blood clearance (0.18%ID/g) and kidney excretion (44%ID/g), resulting in very high contrast (tumor/muscle >200:1). A kit formulation for 99mTc labeling of scFvs targeting mesothelioma was developed based on specific HYNIC conjugation and GH (Glucoheptonate) as a coligand, producing not only high specific activity, but also improved tumor uptake. This convenient one-pot labeling method has the potential for translation into clinical use and is applicable to other scFvs as well.

Authors+Show Affiliations

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia 22908, United States. Department of Radiology and Biomedical Imaging, University of California, San Francisco, California 94143, United States.Department of Radiology and Biomedical Imaging, University of California, San Francisco, California 94143, United States.Department of Anesthesia, University of California, San Francisco, California 94143, United States.Department of Radiology and Biomedical Imaging, University of California, San Francisco, California 94143, United States. UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94143, United States.Department of Anesthesia, University of California, San Francisco, California 94143, United States. UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94143, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32628464

Citation

He, Jiang, et al. "Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma." Bioconjugate Chemistry, vol. 31, no. 7, 2020, pp. 1750-1755.
He J, Feng J, Su Y, et al. Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma. Bioconjug Chem. 2020;31(7):1750-1755.
He, J., Feng, J., Su, Y., Seo, Y., & Liu, B. (2020). Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma. Bioconjugate Chemistry, 31(7), 1750-1755. https://doi.org/10.1021/acs.bioconjchem.0c00319
He J, et al. Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma. Bioconjug Chem. 2020 Jul 15;31(7):1750-1755. PubMed PMID: 32628464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitative 99mTc Labeling Kit for HYNIC-Conjugated Single Chain Antibody Fragments Targeting Malignant Mesothelioma. AU - He,Jiang, AU - Feng,Jinjin, AU - Su,Yang, AU - Seo,Youngho, AU - Liu,Bin, Y1 - 2020/07/06/ PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez SP - 1750 EP - 1755 JF - Bioconjugate chemistry JO - Bioconjug. Chem. VL - 31 IS - 7 N2 - Single chain antibody fragment (scFv) is a promising agent for imaging and targeted therapy. The objective of the study is to evaluate a kit formulation for 99mTc labeling of scFv for tumor imaging. The scFv was engineered to contain a cysteine tag to accommodate the specific conjugation of HYNIC and subsequent 99mTc labeling. The labeling conditions were formulated to allow instantaneous one-pot quantitative labeling. The reproducibility of labeling was evaluated at various time points during kit storage at -20 °C. In vitro cell binding experiments and HPLC analysis were performed to assess binding affinity and radiolabel stability, respectively. In vivo tumor targeting study was performed in xenograft models with biodistribution studied at 1, 3, and 24 h post-injection. The optimized kit with 5 μg SnF2, pH 5.5, and 50 μg GH along with as low as 15 μg of HYNIC-cys-scFv provided high labeling yield (>95%), high specific activity (1.8 × 107 Ci/Mol), and robust reproducibility with shelf life up to 90 days when stored at -20 °C. The in vitro cell binding study showed the labeled scFv maintained the binding capability with an apparent KD of ∼27 nM. The animal study using tumor-bearing mice showed high tumor uptake at 16.9%ID/g 24 h post-injection along with rapid blood clearance (0.18%ID/g) and kidney excretion (44%ID/g), resulting in very high contrast (tumor/muscle >200:1). A kit formulation for 99mTc labeling of scFvs targeting mesothelioma was developed based on specific HYNIC conjugation and GH (Glucoheptonate) as a coligand, producing not only high specific activity, but also improved tumor uptake. This convenient one-pot labeling method has the potential for translation into clinical use and is applicable to other scFvs as well. SN - 1520-4812 UR - https://www.unboundmedicine.com/medline/citation/32628464/Quantitative_99mTc_Labeling_Kit_for_HYNIC-Conjugated_Single_Chain_Antibody_Fragments_Targeting_Malignant_Mesothelioma L2 - https://doi.org/10.1021/acs.bioconjchem.0c00319 DB - PRIME DP - Unbound Medicine ER -
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