Development of a clickable bimodal fluorescent/PET probe for in vivo imaging

Abstract

BackgroundFluorescent imaging agents are becoming evermore important in preclinical and clinical research. They do, however, suffer from poor tissue penetration, which makes optical fluorescence imaging incompatible with whole-body imaging techniques. The design of novel bimodal PET active and fluorescent tracers could therefore combine the benefits of optical imaging with radioactively labeled imaging probes. Herein, we report the synthesis and evaluation of a clickable 18F-labeled fluorescent dye.MethodsAn azide-modified BODIPY-Fl dye could be successfully radio-labeled with 18F using an 18F/19F exchange reaction of the boron-fluoride core of the BODIPY dye to yield a clickable bimodal PET/fluorescent imaging tool. In vitro as well as in vivo imaging (PET/fluorescence) using a bombesin analog was conducted to study the applicability of the dual-modality imaging probe.ResultsWe use the radio-labeled small molecule, 18F-BODIPY-azide to label site-specifically different targeted peptides, based on a standard modular labeling protocol. Following the synthesis of a bimodal bombesin analog, we determine the peptide tracer’s performance in vitro and in vivo, exploring both the optical as well as PET imaging capabilities.ConclusionThis versatile methodology has the potential to have a transformational impact on 18F radiotracer synthesis, opening the door for rapid screening of novel-labeled peptide tracers, both on the cellular (optical) as well as whole-body (PET) level.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0120-4) contains supplementary material, which is available to authorized users.

Synthesis, radiosynthesis and in vitro evaluation of 18F-Bodipy-C16/triglyceride as a dual modal imaging agent for brown adipose tissue

“…Furthermore, downstream metabolic reactions in white adipocytes were already visualized [ 28 ]. Since we did not want to decrease the good binding properties of BDP-FA by introduction of another chelator molecule, we got interested in 18 F/ 19 F exchange reactions used to transform fluorescent dyes into dual-modality PET/fluorescent imaging dyes [ 29 – 33 ]. Because the FA is only modified at the end of the carbon chain, neither an increased steric demand, nor lowering of the targeting efficiency is expected.…”

Dual PET and Near-Infrared Fluorescence Imaging Probes as Tools for Imaging in Oncology

“…This must be considered in image-guided surgical procedures. For this reason, 18 F and 68 Ga isotopes more appropriately match the targeting half-lives of peptides, as in targeting of the SSTR class of somatostatin receptors [2], and PET/Fl probes for BBR gastrin receptors [41]. A recent 64 Cu GLP-1R peptide receptor application is of particular interest for its utility in imaging of 64 Cu-Cy5–labeled exendin-4 peptide at receptors in 916–1 insulinomas in 2–4 hours.…”

“…Unfortunately, these prereacted fluorophore PET synthons (Fig. 2A) are not yet commercially available and require synthetic chemistry expertise to make [41, 52]. …”

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by 18F-positron emitting tomography and fluorescence

“…One good combination is positron emission tomography (PET) and fluorescence imaging. Both 18 F-PET and fluorescence imaging allow the tracking of small molecules at sub-nanomolar concentration, making them among the most sensitive, and therefore also the potentially least toxic, of available imaging modalities [3][4][5][6]. Moreover, while PET emissions can be non-invasively quantitated through a patient's body, fluorescence imaging is ideal for visualizing submicron, histologic structure in superficial tissue.…”