PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments

Abstract

Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first 18F-labeled cyclic RGD peptide as radiotracer for imaging integrin α v β 3 expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, including α 5 β 1 and α v β 6, came into the focus of pharmaceutical radiochemistry. This review will discuss the tracers already evaluated in clinical trials and summarize the preliminary outcome. It will also give an overview on recent developments to further optimize the first-generation compounds such as [18F]Galacto-RGD. This includes recently developed 18F-labeling strategies and also new approaches in 68Ga-complex chemistry. Furthermore, the approaches to develop radiopharmaceuticals targeting integrin α 5 β 1 and α v β 6 will be summarized and discussed.

Novel “Add-On” Molecule Based on Evans Blue Confers Superior Pharmacokinetics and Transforms Drugs to Theranostic Agents

“…As a proof of concept, we conjugated NMEB and DMEB to c(RGDfK), hereafter referred to as arginine-glycine-aspartic acid (RGD) peptide, for targeting cell surface receptor integrin a v b 3 . This integrin receptor is overexpressed in various malignancies and has a crucial role in tumor angiogenesis (7)(8)(9). We demonstrated that either NMEB-RGD or DMEB-RGD could be of use as an imaging agent and as a radiotherapeutic agent for the treatment of integrin a v b 3 -expressing tumors.…”

Development of the Fibronectin–Mimetic Peptide KSSPHSRN(SG)₅RGDSP as a Novel Radioprobe for Molecular Imaging of the Cancer Biomarker α₅β₁ Integrin

“…23) Neubauer et al 24) recently reported on a 68 Galabeled radiotracer based on an aza-glycine derivative of an α 5 β 1 antagonist that was initially characterized by Heckmann et al based on a nonpeptidic tyrosine scaffold. 25) PET imaging of mice bearing an α 5 β 1 -positive tumor and an α V β 3 -positive tumor on each side of the shoulder demonstrated promising results of this peptidomimetic radiotracer for selective imaging of α 5 β 1 .…”

Molecular imaging of integrins in oncology

“…In addition, nanoconstructs for magnetic resonance (MR) imaging or even for multimodal techniques have been developed. [12][13][14][15][16] First, clinical studies employing novel RGD-based scintigraphic probes focus on safety issues, comparability to standard-of-care diagnostics, and the possibility to monitor antiangiogenic therapies. Figure 1 shows the number of publications dealing with integrin imaging in different contexts in the last few decades.…”

“…12,[18][19][20] This review focuses on recent advances of integrin molecular imaging for cancer diagnosis. First, clinical applications are highlighted, and experimental approaches in preclinical research and multimodal setups are also discussed.…”