ImmunoPET Imaging of αβ Expression Using an Engineered Anti-αβ Cys-diabody Site-Specifically Radiolabeled with Cu-64: Considerations for Optimal Imaging with Antibody Fragments.

Purpose: Increased expression of the αβ integrin correlates with advanced tumor grade and poor clinical outcome, identifying αβ as a prognostic indicator and an attractive target for molecular imaging. This work investigated the ability of a disulfide-stabilized [Cu]NOTA-αβ cys-diabody to image αβ expression in vivo using a nu/nu mouse model bearing human melanoma xenografts and positron-emission tomography.

Procedures: Small-animal positron emission tomography (PET) imaging, quantitative ROI analysis, and ex vivo biodistribution were conducted to ascertain tumor uptake and organ distribution of the [Cu]NOTA-αβ cys-diabody.

High-Throughput Approaches to the Development of Molecular Imaging Agents.

Molecular imaging allows for the visualization of changes at the cellular level in diseases such as cancer. A successful molecular imaging agent must rely on disease-selective targets and ligands that specifically interact with those targets. Unfortunately, the translation of novel target-specific ligands into the clinic has been frustratingly slow with limitations including the complex design and screening approaches for ligand identification, as well as their subsequent optimization into useful imaging agents.

The Effect of Bi-Terminal PEGylation of an Integrin αvβ₆-Targeted ¹⁸F Peptide on Pharmacokinetics and Tumor Uptake.

Unlabelled: Radiotracers based on the peptide A20FMDV2 selectively target the cell surface receptor integrin αvβ6. This integrin has been identified as a prognostic indicator correlating with the severity of disease for several challenging malignancies. In previous studies of A20FMDV2 peptides labeled with 4-(18)F-fluorobenzoic acid ((18)F-FBA), we have shown that the introduction of poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in αvβ6-expressing tumors.

Characterization and evaluation of (64)Cu-labeled A20FMDV2 conjugates for imaging the integrin αvβ 6.

Purpose: The integrin αvβ6 is overexpressed in a variety of aggressive cancers and serves as a prognosis marker. This study describes the conjugation, radiolabeling, and in vitro and in vivo evaluation of four chelators to determine the best candidate for (64)Cu radiolabeling of A20FMDV2, an αvβ6 targeting peptide.

Procedures: Four chelators were conjugated onto PEG28-A20FMDV2 (1): 11-carboxymethyl-1,4,8,11-tetraazabicyclo[6.