Pradeep K Garg1,2, Rachid Nazih3,2, Yanjun Wu2, Ravi Singh3,4, Sudha Garg1,2. 1. Department of Radiology, Wake Forest University Medical Center, Winston Salem, North Carolina pgarg@biomed.org. 2. Biomedical Research Foundation, Shreveport, Louisiana; and. 3. Department of Radiology, Wake Forest University Medical Center, Winston Salem, North Carolina. 4. Department of Cancer Biology, Wake Forest University Medical Center, Winston Salem, North Carolina.
Abstract
We report the synthesis and preclinical evaluation of a 11C-labeled probe to target melanoma using PET. Methods: The target compound 4-11C-methoxy N-(2-diethylaminoethyl) benzamide (4-11C-MBZA) was prepared via the 11C-methylation of 4-hydroxy N-(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. Results: 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. Conclusion: 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.
We report the synthesis and preclinical evaluation of a 11C-labeled probe to target melanoma using PET. Methods: The target compound 4-11C-methoxy N-(2-diethylaminoethyl) benzamide (4-11C-MBZA) was prepared via the 11C-methylation of 4-hydroxy N-(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. Results: 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. Conclusion: 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.
Authors: Michael C Bellavia; Lea Nyiranshuti; Joseph D Latoche; Khanh-Van Ho; Ronald J Fecek; Jennifer L Taylor; Kathryn E Day; Shubhanchi Nigam; Michael Pun; Fabio Gallazzi; Robert S Edinger; Walter J Storkus; Ravi B Patel; Carolyn J Anderson Journal: Mol Imaging Biol Date: 2021-10-25 Impact factor: 3.484
Authors: Laetitia Vercellino; Dorine de Jong; Laurent Dercle; Benoit Hosten; Brian Braumuller; Jeeban Paul Das; Aileen Deng; Antoine Moya-Plana; Camry A'Keen; Randy Yeh; Pascal Merlet; Barouyr Baroudjian; Mary M Salvatore; Kathleen M Capaccione Journal: Diagnostics (Basel) Date: 2022-04-29