A Thiol-Reactive ¹⁸F-Labeling Agent, N-[2-(4-¹⁸F-Fluorobenzamido)Ethyl]Maleimide, and Synthesis of RGD Peptide-Based Tracer for PET Imaging of α_vβ₃ Integrin Expression

Cell-binding assay of c(RGDyK), E[c(RGDyK)]₂, FBEM-SRGD, and FBEM-SRGD2 using U87MG cells (integrin α_vβ₃–positive human glioblastoma). The cell-binding affinity of the peptides was determined by performing competitive displacement studies with ¹²⁵I-echistatin. IC₅₀ values for c(RGDyK), E[c(RGDyK)]₂, FBEM-SRGD, and FBEM-SRGD2 were 51.3 ± 4.2, 26.1 ± 3.2, 66.8 ± 5.1, and 55.1 ± 6.5 nmol/L, respectively (n = 6).

Biodistribution of ¹⁸F-FBEM-SRGD (A) and ¹⁸F-FBEM-SRGD2 (B) in athymic nude mice bearing both U87MG and MDA-MB-435 tumors at 10, 30, and 60 min after injection (n = 3). Biodistribution of both tracers at 60 min after injection when coinjected with 10 mg/kg mice body weight of c(RGDyK) is also shown.

Dynamic microPET scans using both radiotracers at different time points in a mouse bearing both U87MG and MDA-MB-435 tumors. Ten-minute static scans at several later time points were also conducted to complete the tracer kinetic study.

Time–activity curves of ¹⁸F-FBEM-SRGD (A) and ¹⁸F-FBEM-SRGD2 (B) obtained from microPET scans. The inflection point for tracer clearance is most likely due to the slower metabolism during the dynamic scan when mice were under anesthesia and body temperature was lowered.

Ten-minute static microPET scans of U87MG tumor-bearing mice (arrows) injected with 3.7 MBq of ¹⁸F-FBEM-SRGD2. (Left) Control mouse. (Right) Blocking with 10 mg/kg mouse body weight of c(RGDyK).