RGD‐based PET tracers for imaging receptor integrin α_vβ₃ expression

Abstract

Positron emission tomography (PET) imaging of receptor integrin αv β3 expression may play a key role in the early detection of cancer and cardiovascular diseases, monitoring disease progression, evaluating therapeutic response, and aiding anti-angiogenic drugs discovery and development. The last decade has seen the development of new PET tracers for in vivo imaging of integrin αv β3 expression along with advances in PET chemistry. In this review, we will focus on the radiochemistry development of PET tracers based on arginine-glycine-aspartic acid (RGD) peptide, present an overview of general strategies for preparing RGD-based PET tracers, and review the recent advances in preparations of (18) F-labeled, (64) Cu-labeled, and (68) Ga-labeled RGD tracers, RGD-based PET multivalent probes, and RGD-based PET multimodality probes for imaging receptor integrin αv β3 expression.

Enzymatic Fluorination and Biotechnological Developments of the Fluorinase

“…In this substrate the pegylated chain links to a cyclic Arg-Gly-Asp (RGD) peptide, a class of peptides relevant to cancer cell identification and clinical imaging. 65 The fluorinase accepted substrate 39 and was able to catalyze its conversion to [ ]-Fluoroacetate 1 has been used as a radiotracer to explore the relative activity of glial neurons in the brain, 66 and it is also being developed as a cancer marker, 67 where it identifies regions of high levels of acetate metabolism in rapidly metabolizing cells. A simple modification of the enzymatic synthesis of [ 18 F]-10 allowed the chemo-enzymatic preparation of [ 18 F]-1.…”

Preclinical Evaluation of a High-Affinity 18F-Trifluoroborate Octreotate Derivative for Somatostatin Receptor Imaging

“…Hence, fluoride must be dried and reacted in dry solvents at high temperature to radiolabel a radioprosthetic that is then conjugated to the peptide in at least 1 additional step. Although such multistep 18 F-labeling reactions are commonplace (24), the relatively short half-life of 18 F-fluoride often impedes the clinical application of multistep reactions, particularly in terms of ensuring specific activity greater than 37 GBq/mmol (.1 Ci/mmol) (25). Given these challenges, an sstr2 ligand that is easily labeled with 18 F-fluoride in high yield and at high specific activity would facilitate sstr2 imaging by PET.…”

Molecular imaging of integrins in oncology

“…20,32,33 Also, special compounds like multivalent RGDbased PET tracers or multimodality probes and labeling with a number of diagnostic or therapeutic nuclides show that a v b 3 is in fact one of the best evaluated diagnostic targets in molecular imaging. 34 One impressive example is an approach combining targeted alpha particle therapy with Cerenkov luminescence imaging (CLI) using the theranostic probe […”