PT  - JOURNAL ARTICLE
AU  - Zhanhong Wu
AU  - Lin Li
AU  - Shuanglong Liu
AU  - Fumiko Yakushijin
AU  - Kenichi Yakushijin
AU  - David Horne
AU  - Peter S. Conti
AU  - Zibo Li
AU  - Fouad Kandeel
AU  - John E. Shively
TI  - Facile Preparation of a Thiol-Reactive <sup>18</sup>F-Labeling Agent and Synthesis of <sup>18</sup>F-DEG-VS-NT for PET Imaging of a Neurotensin Receptor–Positive Tumor
AID  - 10.2967/jnumed.114.137489
DP  - 2014 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1178--1184
VI  - 55
IP  - 7
4099  - http://jnm.snmjournals.org/content/55/7/1178.short
4100  - http://jnm.snmjournals.org/content/55/7/1178.full
SO  - J Nucl Med2014 Jul 01; 55
AB  - Accumulating evidence suggests that neurotensin receptors (NTRs) play key roles in cancer growth and survival. In this study, we developed a simple and efficient method to radiolabel neurotensin peptide with 18F for NTR-targeted imaging. Methods: The thiol-reactive reagent 18F-(2-(2-(2-fluoroethoxy)ethoxy)ethylsulfonyl)ethane (18F-DEG-VS) was facilely prepared through 1-step radiofluorination. After high-pressure liquid chromatography purification, 18F-DEG-VS was incubated with the c(RGDyC) and c(RGDyK) peptide mixture to evaluate its specificity toward the reactive thiol. Thiolated neurotensin peptide was then labeled with 18F using this novel synthon, and the resulting imaging probe was subjected to receptor-binding assay and small-animal PET studies in a murine xenograft model. The imaging results and metabolic stability of 18F-DEG-VS-NT were compared with the thiol-specific maleimide derivative N-[2-(4-18F-fluorobenzamido)ethyl]maleimide-neurotensin (18F-FBEM-NT). Results: 18F-DEG-VS was obtained in high labeling yield. The reaction of 19F-DEG-VS was highly specific for thiols at neutral pH, whereas the lysine of c(RGDyK) reacted at a pH greater than 8.5. 18F-DEG-VS-c(RGDyC) was the preferred product when both c(RGDyK) and c(RGDyC) were incubated together with 18F-DEG-VS. Thiolated neurotensin peptide (Cys-NT) efficiently reacted with 18F-DEG-VS, with a 95% labeling yield (decay-corrected). The radiochemical purity of the 18F-DEG-VS-NT was greater than 98%, and the specific activity was about 19.2 ± 4.3 TBq/mmol. Noninvasive small-animal PET demonstrated that 18F-DEG-VS-NT had an NTR-specific tumor uptake in subcutaneous HT-29 xenografts. The tumor-to-muscle, tumor-to-liver, and tumor-to-kidney ratios reached 30.65 ± 22.31, 11.86 ± 1.98, and 1.91 ± 0.43 at 2 h after injection, respectively, based on the biodistribution study. Receptor specificity was demonstrated by blocking experiment. Compared with 18F-FBEM-NT, 18F-DEG-VS-NT was synthesized with fewer steps and provided significantly improved imaging quality in vivo. Conclusion: We have established a facile 18F-labeling method for site-specific labeling of the Cys-NT. Using this method, we synthesized an NTR-targeted PET agent, which demonstrated high tumor-to-background contrast.