Evaluation of ¹⁸F-DEG-VS-NT as a PET probe for NTR1 targeted imaging

Objectives Accumulating evidence suggests that neurotensin receptors (NTRs) play key roles in cancer growth and survival. In this study, we developed an ¹⁸F labeled neurotensin peptide for NTR1 targeted imaging.

Methods ¹⁸F labeling of thiolated neurotensin peptide was then performed using our newly developed ¹⁸F-vinyl sulfone synthon. The resulting imaging probe was subjected to receptor-binding assay and microPET studies in murine xenograft models.

Results Thiolated neurotensin peptide could be efficiently labeled with ¹⁸F-DEG-VS with 95% labeling yield (decay-corrected on the basis of ¹⁸F-DEG-VS). The radiochemical purity of the ¹⁸F-DEG-VS-NT was >98% and the specific activity was 100∼150 TBq/mmol. Noninvasive microPET demonstrated that ¹⁸F-DEG-VS-NT had NTR-specific tumor uptake in subcutaneous HT-29 xenografts. The tumor to muscle, tumor to liver, and tumor to kidney ratio could reach 27.12, 10.33, and 3.69 at 2 hr p.i. respectively. Receptor specificity was successfully demonstrated by blocking experiment.

Conclusions Through the ¹⁸F-vinyl sulfone synthon, a NTR1 targeted PET imaging agent was synthesized, which demonstrated specific tumor uptake and superior tumor to background contrast. The elevated tumor to major organ uptake ratios (including tumor/kidney) lead to high contrast images in vivo.