4-¹¹C-Methoxy <i>N</i>-(2-Diethylaminoethyl) Benzamide: A Novel Probe to Selectively Target Melanoma.

Abstract

We report the synthesis and preclinical evaluation of a ¹¹C-labeled probe to target melanoma using PET. <b>Methods:</b> The target compound 4-¹¹C-methoxy <i>N</i>-(2-diethylaminoethyl) benzamide (4-¹¹C-MBZA) was prepared via the ¹¹C-methylation of 4-hydroxy <i>N</i>-(2-diethylaminoethyl) benzamide (4-HBZA). The in vitro binding was performed using B16F1 (melanoma cells), MCF-10A (breast epithelial cells), and MDA-MB 231 (breast cancer cells). The internalization studies were conducted using B16F1 cells. In vivo biodistribution and small-animal PET imaging were performed in mice bearing B16F1 melanoma tumor xenografts. <b>Results:</b> The target compound 4-¹¹C-MBZA was prepared in 46% ± 7% radiochemical yields by reacting ¹¹C-methyltriflate with 4-HBZA followed by high-performance liquid chromatography purification. The specific activity of this compound was 853 ± 29.6 GBq/μmol (23 ± 0.8 Ci/μmol). The binding of 4-¹¹C-MBZA to B16F1, MCF-10A, and MDA-MB-231 cells was 6.41% ± 1.28%, 1.51% ± 0.17%, and 0.30% ± 0.17%, respectively. Internalization studies using B16F1 melanoma cells show 60.7% of the cell-bound activity was internalized. Results from biodistribution studies show a rapid and high uptake of radioactivity in the tumor, with uptake levels reaching 5.85 ± 0.79 and 8.13 ± 1.46 percentage injected dose per gram at 10 and 60 min, respectively. Low uptake in normal tissues in conjunction with high tumor uptake resulted in high tumor-to-tissue ratios. On small-animal PET images, the tumor was clearly delineated soon after 4-¹¹C-MBZA injection and tumor uptake reached 4.2 percentage injected dose per gram by 20 min. These preclinical evaluations show a high propensity of 4-¹¹C-MBZA toward melanoma tumor. <b>Conclusion:</b> We successfully developed 4-¹¹C-MBZA as a PET imaging probe, displaying properties advantageous over those for its ¹⁸F analogs. These preclinical evaluation results demonstrate the clinical potential of this probe to selectively target melanoma.