Comparison of Fully Automated Computer Analysis and Visual Scoring for Detection of Coronary Artery Disease from Myocardial Perfusion SPECT in a Large Population
| Autor: | Reza Arsanjani, Piotr J. Slomka, Mark Lemley, Guido Germano, Sharmila Dorbala, Mathews B. Fish, Yuan Xu, Sean W. Hayes, Daniel S. Berman, James Gerlach |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Quality Control Technetium Tc 99m Sestamibi Pathology medicine.medical_specialty Biodistribution Coronary Artery Disease Pharmacology Coronary Angiography Article chemistry.chemical_compound Prostate cancer In vivo PEG ratio Image Processing Computer-Assisted medicine Humans Radiology Nuclear Medicine and imaging Aged Observer Variation Tomography Emission-Computed Single-Photon Electronic Data Processing business.industry Myocardium Coronary Stenosis Reproducibility of Results Bombesin Binding potential Middle Aged medicine.disease Radiography Perfusion medicine.anatomical_structure ROC Curve chemistry Area Under Curve Female Pancreas business Software |
| Zdroj: | Journal of Nuclear Medicine. 54:221-228 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.112.108969 |
| Popis: | 221 Objectives Overexpression of gastrin-releasing peptide receptor (GRPR) has been shown in prostate cancer. More hydrophilic peptides can increase the receptor mediated binding affinity. Three derivatives of F-18 bombesin, with 0, 1, and 2 PEG groups were synthesized and evaluated in vivo to determine the GRPR binding potential in PC-3 tumor-bearing mice. Methods The GRPR-binding peptides F-ALK-BBN, F-ALK-BBN-PEG, and F-PEG-BBN-PEG were prepared from their azide-modified precursors by the copper-catalyzed azide-alkyne cycloaddition conjugation to the acetylene-bearing 2-[18F]fluoropyridines ([18F]FP5yne and PEG-[18F]FPyKYNE). Binding affinity (Ki) of the peptides was measured by competition binding assays using PC-3 cells. Biodistribution and µPET imaging studies were performed on PC-3 tumor-bearing mice with and without blocking. Results Excellent Ki of 0.2 nM was attained for PEGylated derivatives, which showed an improved binding affinity compared to 19F-ALK-BBN. Low tumor and pancreas uptake was seen in biodistribution studies of [18F]F-ALK-BBN, whereas both PEGylated derivatives showed an improved uptake in tumors and pancreas. The %ID/g of tumors at 15, 30 and 60 min post injection were 2.0 ± 0.3, 1.4 ± 0.5 and 1.0 ± 0.1 in [18F]F-ALK-BBN-PEG, and 2.0 ± 0.1, 1.9 ± 0.4 and 1.1 ± 0.5 in [18F]F-PEG-BBN-PEG. However, tumor to blood ratio of [18F]F-ALK-BBN-PEG at 1h post injection was 2 folds higher than that of [18F]F-PEG-BBN-PEG. Uptake of pancreas was 1.7 folds higher in [18F]F-PEG-BBN-PEG. In blocking studies uptake of both pancreas and tumor were significantly reduced. Conclusions An improved GRP receptor-mediated tumor uptake was achieved in both PEGylated F-18 labeled bombesin derivatives and less hepatobiliary excretion was observed. Slower blood elimination was observed in [18F]F-PEG-BBN-PEG. However [18F]F-ALK-BBN-PEG showed better tumor visualization in µPET imaging with higher tumor to blood ratios. |
| Databáze: | OpenAIRE |
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