Radiosynthesis and evaluation of a <SUP>68</SUP>Ga-labeled brominated benzamide derivative for detection of melanoma in small animals

Abstract

Malignant melanoma has the highest mortality rate of any skin cancer due to its aggressive nature and high potential for metastasis, and early diagnosis is critical for improving outcomes because of the limited treatment options available for patients. We synthesized a brominated benzamide derivative labeled with( 68)Ga and evaluated its biological properties as an imaging agent for detecting melanoma using positron emission tomography (PET). The eluted( 68)Ga was dissolved in 1.0 M NaOAc buffer and labeled with the synthesized precursor. The radiochemical yield and radiochemical purity of the 68Ga chelation complex were confirmed by radio-thin layer chromatography. In vitro uptake was measured in the murine melanoma cell line (B16F10), and in vivo studies were performed with B16F10-bearing mice. The total radiochemical yield was over 95% (n > 3), and the radiochemical purity was above 98%. The 68Ga-labeled compound showed high uptake in B16F10 cells activated with l-tyrosine (2 mM) (6561.48 +/- 1067.52 counts per minute [CPM] at 30 min, 8987.03 +/- 888.64 CPM at 60 min). The labeled compound allowed visualization of B16F10 xenografts on microPET at 60 min after intravenous injection (tumor uptake: 1.20 +/- 0.20% ID/g at 30 min, 0.91 +/- 0.24% ID/g at 60 min). These results suggest that Ga-68-labeled 2,2 ',2 '',2 & tprime;-(2-(4-(3-(2-((2-(5-bromopicolinamido)ethyl)(methyl)amino)ethyl)thioureido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (Ga-68-MI-0202E1) has potential as a PET imaging probe for the detection of melanoma.