PET Imaging of VEGFR with a Novel ⁶⁴Cu-Labeled Peptide

Abstract

Vascular endothelial growth factor receptors (VEGFRs) are well recognized as significant biomarkers of tumor angiogenesis. Herein, we have developed a first-of-its-kind peptide-based VEGFR positron emission tomography (PET) tracer. The novel [ 64 Cu]VEGF 125−136 peptide possessed satisfactory radio-characteristics and showed good specificity for the visualization of VEGFR in various mouse models, in which the tumorspecific radioactivity uptake was highly correlated to the VEGFR expression level. Moreover, the tracer showed high tumor uptake (ca. 5.89 %ID/g at 20 min postinjection in B16F10 mice) and excellent pharmacokinetics, achieving the maximum imaging quality within 1 h after injection. These features convey [ 64 Cu]VEGF 125−136 as a promising, clinically translatable PET tracer for the imaging of tumor angiogenesis.

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging

“…Unlike anatomical imaging techniques such as X-ray, ultrasound and magnetic resonance imaging (MRI), PET offers the real-time biological processes in molecular level based on a specific ligand bearing a positron-emitting radionuclide (“PET tracer”), which makes this technology with high sensitivity and excellent tissue penetration 34 . The commonly used positron radionuclides consist of 11 C ( t 1/2 = 20.4 min), 18 F ( t 1/2 = 109.7 min), 68 Ga ( t 1/2 = 67.6 min), 64 Cu ( t 1/2 = 12.8 h) and 89 Zr ( t 1/2 = 78.4 h) 35 , the former two isotopes are most widely used for labeling small organic molecules 36 , 37 , while the metal radionuclides are more feasible to label peptide 38 , 39 , antibody 40 , 41 and nano materials 42 . Another advantage of PET is that the amount of radiotracer used in imaging studies is very low (10 −6 ‒10 −9 g; microdosing), which is feasible to evaluate the biological process without pharmacological effects, as well as to enable rapidly translation of promising radiotracers from bench work to phase 0 clinical trials 43 .…”

Development of a Stable Peptide-Based PET Tracer for Detecting CD133-Expressing Cancer Cells

“… 11 , 29 − 33 Among them, N-terminal modification is an effective and direct way to ameliorate peptide stability. 8 , 14 , 34 Moreover, it generally preserves the specific binding mode of the original peptide. We therefore synthesized a peptide called CM-2, in which a 6-aminohexanoic acid (Ahx) linker is anchored between the N terminus of the peptide and the DOTA ( Figure 1 A).…”

Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint

“…Radiolabelling was then performed according to the method reported previously. 45,46 As shown in Table 1, the labeling of both of the peptides achieved high radiochemical yields (490% (Fig. S1, ESI †).…”