The integrin a v b 3 receptor is upregulated on tumor cells and endothelium and plays important roles in angiogenesis and metastasis. Arg-Gly-Asp (RGD) peptide ligands have high affinity for these integrins and can be radiolabeled for PET imaging of angiogenesis or tumor development. We have assessed the safety, stability, and tumor distribution kinetics of a novel radiolabeled RGD-based integrin peptide-polymer conjugate, 18 F-AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET. Methods: The biodistribution of 18 F-AH111585 was assessed in 18 tumor lesions from 7 patients with metastatic breast cancer by PET, and the PET data were compared with CT results. The metabolic stability of 18 F-AH111585 was assessed by chromatography of plasma samples. Regions of interest (ROIs) defined over tumor and normal tissues of the PET images were used to determine the kinetics of radioligand binding in tissues. Results: The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the 18 F-AH111585 PET images, either as distinct increases in uptake compared with the surrounding normal tissue or, in the case of liver metastases, as regions of deficit uptake because of the high background activity in normal liver tissue. 18 F-AH111585 was either homogeneously distributed in the tumors or appeared within the tumor rim, consistent with the pattern of viable peripheral tumor and central necrosis often seen in association with angiogenesis. Increased uptake compared with background (P 5 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor. Conclusion: 18 F-AH111585 designed to bind the a v b 3 integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.
There is an unmet need to develop imaging methods for the early and objective assessment of breast tumors to therapy. 18 F]FLT (K i ) ranged from 0.6 to 10.4 Â 10 À4 and from 0 to 0.6 Â 10 À4 mL plasma cleared/s/mL tissue in tumor (29 regions, 15 patients) and normal tissues, respectively. Tumor K i and fractional retention of radiotracer determined by spectral analysis correlated with Ki-67 labeling index (r = 0.92, P < 0.0001 and r = 0.92, P < 0.0001, respectively). These correlations were superior to those determined by semiquantitative methods. We conclude that [ 18 F]FLT-positron emission tomography is a promising clinical tool for imaging cellular proliferation in breast cancer, and is most predictive when analyzed by graphical and spectral methods. (Cancer Res 2005; 65(21): 10104-12)
Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 (18)F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists' criteria for TA. (18)F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that (18)F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment.
PET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients.
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