ah-111585 and Breast-Neoplasms

The integrin alpha v beta3 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, 18F-AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET.. The biodistribution of 18F-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 18F-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.. The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the 18F-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. 18F-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 = 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor.. 18F-AH111585 designed to bind the alpha v beta3 integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.

Topics: Adult; Aged; Breast Neoplasms; Female; Humans; Metabolic Clearance Rate; Middle Aged; Oligopeptides; Organ Specificity; Peptides; Polyethylene Glycols; Positron-Emission Tomography; Radiopharmaceuticals; Tissue Distribution

The purpose of the study was to estimate the receptor-ligand binding of an arginine-glycine-aspartic acid (RGD) peptide in somatic tumours. To this aim, we employed dynamic positron emission tomography (PET) data obtained from breast cancer patients with metastases, studied with the α(v)β(3/5) integrin receptor radioligand [(18)F]fluciclatide.. First, compartmental modelling and spectral analysis with arterial input function were performed at the region of interest (ROI) level in healthy lung and liver, and in lung and liver metastases; compartmental modelling was also carried out at the pixel level. The selection of the most appropriate indexes for tumour/healthy tissue differentiation and for estimation of specific binding was then assessed.. The two-tissue reversible model emerged as the best according to the Akaike Information Criterion. Spectral analysis confirmed the reversibility of tracer kinetics. Values of kinetic parameters, estimated as mean from parametric maps, correlated well with those computed from ROI analysis. The volume of distribution V(T) was on average higher in lung metastases than in the healthy lung, but lower in liver metastases than in the healthy liver. In agreement with the expected higher α(v)β(3/5) expression in pathology, k(3) and k(3)/k(4) were both remarkably higher in metastases, which makes them more suitable than V(T) for tumour/healthy tissue differentiation. The ratio k(3)/k(4), in particular, appeared a reasonable measure of specific binding.. Besides establishing the best quantitative approaches for the analysis of [(18)F]fluciclatide data, this study indicated that the k(3)/k(4) ratio is a reasonable measure of specific binding, suggesting that this index can be used to estimate α(v)β(3/5) receptor expression in oncology, although further studies are necessary to validate this hypothesis.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Female; Fluorine Radioisotopes; Humans; Middle Aged; Peptides; Polyethylene Glycols; Protein Binding; Protein Interaction Mapping; Radiopharmaceuticals