Evaluation of ^sup 64^Cu-labeled disintegrin for imaging tumor metastasis in an experimental model of human prostate cancer

• Published in: The Journal of nuclear medicine (1978) Vol. 58; p. 921
• Main Authors: Jadvar, Hossein, Chen, Kai, Park, Ryan, Swenson, Steve, Markland, Frank
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.05.2017
• Subjects: Acetic acid; Ammonium; Ammonium acetate; Animal models; Bioluminescence; Chelation; Computed tomography; Conjugation; Emitters; Injection; Integrins; Liver; Medical imaging; Metastases; Metastasis; Muscles; Nuclear medicine; Peptides; Positron emission; Prostate cancer; Quantitative analysis; Radiochemical analysis; Tomography; Tumors; Ultrasound; Ventricle
• ISSN: 0161-5505; 1535-5667

Objectives: A sequence-engineered peptide, vicrostatin (VCN), reliably produced in large quantity in a recombinant bacterial system exhibits high binding affinity to a broad range of human integrins. In this study, we prepared a 64Cu-labeled VCN probe and evaluated its imaging properties in an experimental metastatic model of prostate cancer (PC). Methods: Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was modified with a PEG unit, and followed by conjugation with VCN. The precursor was then radiolabeled with positron emitter 64Cu (t1/2 = 12.7h) in ammonium acetate buffer to provide 64Cu-Sar-PEG-VCN, which was subsequently subject to animal studies in an intracardiac metastatic model of PC. For ease of monitoring tumor growth and spread, PC3luc cells were injected into the left ventricle of the mouse under ultrasound guidance. After 10-14 days of injection, the metastatic model was first validated by bioluminescence imaging (BLI), and then used for evaluation of 64Cu-Sar-PEG-VCN with PET-CT. Results: The preparation of 64Cu-Sar-PEG-VCN was achieved in 75% yield (decay-corrected) with radiochemical purity of >98%. The specific activity of 64Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. The BLI data demonstrated successful establishment of the intracardiac metastatic model of PC. MicroPET-CT imaging results showed that 64Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in the metastatic model, producing high tumor-to-muscle imaging contrast ratio (2.65) and good tumor-to-liver ratio (0.51) at 2 h post-injection. The biodistribution results were consistent with the quantitative analysis of microPET imaging. The integrin expression of prostate tumors was further confirmed by the immunochemistry staining. Conclusion: 64Cu-Sar-PEG-VCN has the potential for in vivo imaging of metastatic PC with PET, which may provide a unique non-invasive method to quantitatively localize and characterize metastatic PC. The efficacy of 64Cu-Sar-PEG-VCN in measuring response to chemotherapeutic treatment in experimental metastatic PC models and use as an imaging theranostic companion with VCN as the therapeutic component is underway.