RT Journal Article SR Electronic T1 Novel RGD peptide derivatives with enhanced pharmacokinetics for PET imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 508 OP 508 VO 56 IS supplement 3 A1 Hernandez, Reinier A1 Chakravarty, Rubel A1 Yang, Yunan A1 Graves, Stephen A1 Nickles, Robert A1 Cai, Weibo YR 2015 UL http://jnm.snmjournals.org/content/56/supplement_3/508.abstract AB 508 Objectives To demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers (targeting integrin αvβ3) can offer advantages in image contrast, time for imaging, and low uptake in non-target tissues.Methods Two c(RGDfk) derivatives, (PEG)2-RGD and PEG4-SAA4-RGD, were constructed using solid-phase synthesis, and conjugated to NOTA for 64Cu-labeling. Competitive cell binding assays (125I-echistatin as the ligand) were performed to determine/compare integrin αvβ3 binding affinity of these peptides. Athymic nude mice bearing U87MG human glioblastoma tumors (integrin αvβ3+) were intravenously injected with each tracer, and dynamic PET scans were acquired during the first 30 min post-injection (p.i.). Static scans were performed at later time points to study long-term biodistribution of the tracers. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers.Results Three tracers, 64Cu-NOTA-c(RGDfk) (1), 64Cu-NOTA-(PEG)2-RGD (2), and 64Cu-NOTA-PEG4-SAA4-RGD (3), were prepared with high purity and radiolabeling yield (>95%). Integrin αvβ3 binding affinities for 1, 2, and 3 were comparable at IC50 values of 507, 444, and 288 nM respectively. Dynamic PET data unveiled similar circulation t1/2 for 2 and 3 (4.8 and 4.1 min respectively), and peak U87MG tumor uptake of ~4 %ID/g at 10 min p.i. for both tracers. Due to its marked hydrophilicity, 3 had faster clearance from tumor and normal tissues while maintaining excellent tumor-to-background ratios at 30 min p.i. (~ 16). Static PET scans at later time points corroborated the enhanced excretion of 3, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the specificity of 3 for integrin αvβ3.Conclusions We developed 2 novel RGD peptide derivatives with optimized pharmacokinetic properties that allow for fast, high contrast PET imaging of integrin αvβ3. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake of other PET tracers.