title: 4-11C-MethoxyN-(2-Diethylaminoethyl) Benzamide: A Novel Probe to Selectively Target Melanoma.
abstract: We report the synthesis and preclinical evaluation of a11C-labeled probe to target melanoma using PET.Methods:The target compound 4-11C-methoxyN-(2-diethylaminoethyl) benzamide (4-11C-MBZA) was prepared via the11C-methylation of 4-hydroxyN-(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 reacting11C-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 its18F analogs. These preclinical evaluation results demonstrate the clinical potential of this probe to selectively target melanoma.
authors.affiliation: Department of Radiology, Wake Forest University Medical Center, Winston Salem, North Carolina pgarg@biomed.org.|Biomedical Research Foundation, Shreveport, Louisiana; and.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Garg
authors.affiliation: Department of Radiology, Wake Forest University Medical Center, Winston Salem, North Carolina.|Biomedical Research Foundation, Shreveport, Louisiana; and.
authors.forename: Rachid
authors.initials: R
authors.lastname: Nazih
authors.affiliation: Biomedical Research Foundation, Shreveport, Louisiana; and.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Radiology, Wake Forest University Medical Center, Winston Salem, North Carolina.|Department of Cancer Biology, Wake Forest University Medical Center, Winston Salem, North Carolina.
authors.forename: Ravi
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Radiology, Wake Forest University Medical Center, Winston Salem, North Carolina pgarg@biomed.org.|Biomedical Research Foundation, Shreveport, Louisiana; and.
authors.forename: Sudha
authors.initials: S
authors.lastname: Garg
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D007553:Isotope Labeling; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D015336:Molecular Probe Techniques; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C000619836:4-methoxy-N-(2-diethylaminoethyl)benzamide; D001549:Benzamides; D019275:Radiopharmaceuticals
keywords: C-11methoxybenzamide; biodistribution; cell binding; melanoma; microPET imaging