Preclinical evaluation of a (64)Cu-labeled disintegrin for PET imaging of prostate cancer
| Autor: | Ryan Park, Steve Swenson, Li-Peng Yap, Francis S. Markland, Hossein Jadvar, Ivetta Vorobyova, Kai Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Biodistribution Angiogenesis Disintegrins Clinical Biochemistry Integrin Drug Evaluation Preclinical Mice Nude Biochemistry Peptides Cyclic Article Polyethylene Glycols 03 medical and health sciences Prostate cancer Mice Heterocyclic Compounds PEG ratio medicine Disintegrin Animals Humans Tissue Distribution 030102 biochemistry & molecular biology biology Chemistry Organic Chemistry Prostatic Neoplasms Sarcosine medicine.disease Xenograft Model Antitumor Assays In vitro 030104 developmental biology Copper Radioisotopes Organ Specificity Positron-Emission Tomography PC-3 Cells Cancer research biology.protein Radiopharmaceuticals Preclinical imaging |
| Zdroj: | Amino Acids |
| Popis: | A novel recombinant disintegrin, vicrostatin (VCN), displays high binding affinity to a broad range of human integrins in substantial competitive biological advantage over other integrin-based antagonists. In this study, we synthesized a new (64)Cu-labeled VCN probe and evaluated its imaging properties for prostate cancer in PC-3 tumor bearing mice. Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was conjugated with PEG unit, and followed by a coupling with VCN. The precursor was then radiolabeled with positron emitter (64)Cu (t(1/2) = 12.7h) in ammonium acetate buffer to provide (64)Cu-Sar-PEG-VCN, which was subsequently subject to in vitro studies, small animal PET, and biodistribution studies. The PC-3 tumor targeting efficacy of (64)Cu-Sar-PEG-VCN was compared to a cyclic RGD peptide based PET probe ((64)Cu-Sar-RGD). (64)Cu labeling was achieved in 75% decay-corrected yield with radiochemical purity of >98%. The specific activity of (64)Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. MicroPET imaging results showed that (64)Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in PC-3 tumor xenografts. As compared to (64)Cu-Sar-RGD, (64)Cu-Sar-PEG-VCN produces higher tumor-to-muscle (T/M) imaging contrast ratios at 2 h (4.66 ± 0.34 vs. 2.88 ± 0.46) and 24 h (4.98 ± 0.80 vs. 3.22 ± 0.30) post-injection (pi), and similar tumor-to-liver ratios at 2 h (0.43 ± 0.09 vs. 0.37 ± 0.04) and 24 h (0.57 ± 0.13 vs. 0.52 ± 0.07) pi. The biodistribution results were consistent with the quantitative analysis of microPET imaging, demonstrating good T/M ratio (2.73 ± 0.36) of (64)Cu-Sar-PEG-VCN at 48 h pi in PC-3 tumor xenografts. For both microPET and biodistribution studies at 48 h pi, the PC-3 tumor uptake of (64)Cu-Sar-PEG-VCN is lower than that of (64)Cu-Sar-RGD. (64)Cu-Sar-PEG-VCN has the potential for in vivo imaging of prostate cancer with PET, which may provide a unique non-invasive method to quantitatively localize and characterize prostate cancer. |
| Databáze: | OpenAIRE |
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