PET imaging of VPAC1 expression in experimental and spontaneous prostate cancer
| Autor: | Christopher Kim, Mathew L. Thakur, Chirag A. Patel, Kaijun Zhang, Christopher Cardi, Mohan R. Aruva, Satish Rattan, Nylla Shanthly, Eric Wickstrom, Peter McCue |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Pathology medicine.medical_specialty Receptors Vasoactive Intestinal Polypeptide Type I Vasoactive intestinal peptide Transplantation Heterologous Mice Nude Mice Transgenic Adenocarcinoma In Vitro Techniques Article Prostate cancer Mice Prostate In vivo Cell Line Tumor Medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution Receptor Intraepithelial neoplasia business.industry Prostatic Neoplasms Histology Organotechnetium Compounds medicine.disease Blood proteins medicine.anatomical_structure Copper Radioisotopes Positron-Emission Tomography Radiopharmaceuticals business Neoplasm Transplantation Vasoactive Intestinal Peptide |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 49(1) |
| ISSN: | 0161-5505 |
| Popis: | Among U.S. men, prostate cancer (PC) accounts for 29% of all newly diagnosed cancers. A reliable scintigraphic agent to image PC and its metastatic or recurrent lesions and to determine the effectiveness of its treatment will contribute to the management of this disease. All PC overexpresses VPAC1 receptors. This investigation evaluated a probe specific for a (64)Cu-labeled receptor for PET imaging of experimental human PC in athymic nude mice and spontaneously grown PC in transgenic mice.The probe, TP3939, was synthesized, purified, and labeled with (64)Cu and (99m)Tc. Using a muscle relaxivity assay, biologic activity was assessed and inhibitory concentrations of 50% calculated. Receptor affinity (Kd) for human PC3 cells was determined using (99m)Tc-TP3939 and (64)CuCl(2.) Blood clearance and in vivo stability were studied. After intravenous administration of either (64)Cu-TP3939 or (64)CuCl(2) in PC3 xenografts and in transgenic mice, PET/CT images were acquired. Prostate histology served as the gold standard. Organ distribution studies (percentage injected dose per gram [%ID/g]) in normal prostate were performed. The ratios of tumor to muscle, tumor to blood, normal prostate to muscle, and tumor to normal prostate were determined.Chemical and radiochemical purities of TP3939 were 96.8% and 98% +/- 2%, respectively. Inhibitory concentrations of 50% and affinity constants were 4.4 x 10(-8) M and 0.77 x 10(-9) M, respectively, for TP3939 and 9.1 x 10(-8) M and 15 x 10(-9) M, respectively, for vasoactive intestinal peptide 28. Binding of (64)CuCl(2) to PC3 was nonspecific. Blood clearance was rapid. In vivo transchelation of (64)Cu-TP3939 to plasma proteins was less than 15%. (64)Cu-TP3939 uptake in PC was 7.48 +/- 3.63 %ID/g at 4 h and 5.78 +/- 0.66 %ID/g at 24 h after injection and was significantly (P0.05) greater than with (64)CuCl(2) (4.79 +/- 0.34 %ID/g and 4.03 +/- 0.83 %ID/g at 4 and 24 h, respectively). The ratios of PC to normal prostate at 4 and 24 h were 4 and 2.7, respectively. (64)Cu-TP3939 distinctly imaged histologic grade IV prostate intraepithelial neoplasia in transgenic mice, but (18)F-FDG and CT did not.Data indicate that TP3939, with its uncompromised biologic activity, delineated xenografts and cases of occult PC that were not detectable with (18)F-FDG. (64)Cu-TP3939 is a promising probe for PET imaging of PC. It may also be useful for localizing recurrent lesions and for determining the effectiveness of its treatment. |
| Databáze: | OpenAIRE |
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