Development and Characterization of 99mTc-scFvD2B as a Potential Radiopharmaceutical for SPECT Imaging of Prostate Cancer

Author:

Bolzati Cristina1ORCID,Gobbi Carolina1,Ferro-Flores Guillermina2ORCID,Turato Sofia3,Ocampo-Garcia Blanca2ORCID,Carpanese Debora3,Marzano Cristina4ORCID,Spolaore Barbara4ORCID,Fracasso Giulio5ORCID,Rosato Antonio36ORCID,Meléndez-Alafort Laura3ORCID

Affiliation:

1. Institute of Condensed Matter Chemistry and Energy Technologies, Consiglio Nazionale delle Ricerche, Corso Stati Uniti 4, 35127 Padova, Italy

2. Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos, Instituto Nacional de Investigaciones Nucleares, Carretera México-Toluca S/N. La Marquesa, Ocoyoacac 52750, Mexico

3. Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64, 35138 Padova, Italy

4. Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy

5. Dipartimento di Scienze Biomediche, Università degli Studi di Padova, Viale G. Colombo 3, 35131 Padova, Italy

6. Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche, Università degli Studi di Padova, Via Gattamelata 64, 35138 Padova, Italy

Abstract

Previously, we demonstrated that the 177Lu-labeled single-chain variable fragment of an anti-prostate-specific membrane antigen (PSMA) IgG D2B antibody (scFvD2B) showed higher prostate cancer (PCa) cell uptake and tumor radiation doses compared to 177Lu-labeled Glu-ureide-based PSMA inhibitory peptides. To obtain a 99mTc-/177Lu-scFvD2B theranostic pair, this research aimed to synthesize and biochemically characterize a novel 99mTc-scFvD2B radiotracer. The scFvD2B-Tag and scFvD2B antibody fragments were produced and purified. Then, two HYNIC derivatives, HYNIC-Gly-Gly-Cys-NH2 (HYNIC-GGC) and succinimidyl-HYNIC (S-HYNIC), were used to conjugate the scFvD2B-Tag and scFvD2B isoforms, respectively. Subsequently, chemical characterization, immunoreactivity tests (affinity and specificity), radiochemical purity tests, stability tests in human serum, cellular uptake and internalization in LNCaP(+), PC3-PIP(++) or PC3(−) PCa cells of the resulting unlabeled HYNIC-scFvD2B conjugates (HscFv) and 99mTc-HscFv agents were performed. The results showed that incorporating HYNIC as a chelator did not affect the affinity, specificity or stability of scFvD2B. After purification, the radiochemical purity of 99mTc-HscFv radiotracers was greater than 95%. A two-sample t-test of 99mTc-HscFv1 and 99mTc-HscFv1 uptake in PC3-PIP vs. PC3 showed a p-value < 0.001, indicating that the PSMA receptor interaction of 99mTc-HscFv agents was statistically significantly higher in PSMA-positive cells than in the negative controls. In conclusion, the results of this research warrant further preclinical studies to determine whether the in vivo pharmacokinetics and tumor uptake of 99mTc-HscFv still offer sufficient advantages over HYNIC-conjugated peptides to be considered for SPECT/PSMA imaging.

Funder

5 per mille 2019

Italian Association for Cancer Research

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference41 articles.

1. Current status of theranostics in prostate cancer;Virgolini;Eur. J. Nucl. Med. Mol. Imaging,2018

2. Prostate cancer-specific PET radiotracers: A review on the clinical utility in recurrent disease;Evans;Pract. Radiat. Oncol.,2018

3. Glu-Ureido-Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers;Kopka;J. Nucl. Med.,2017

4. PSMA PET and radionuclide therapy in prostate cancer;Bouchelouche;Semin. Nucl. Med.,2016

5. Procedure Guideline for Prostate Cancer Imaging with PSMA-ligand PET/CT;Eiber;Nuklearmedizin,2023

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3