Abstract
BackgroundThe purpose of this study was to develop a positron emission tomography (PET) imaging probe that is easy to synthesize and selectively targets melanoma in vivo. Herein, we report the synthesis and preclinical evaluation of N-(2-diethylaminoethyl) 4-[18F]Fluoroethoxy benzamide (4-[18F]FEBZA).A one-step synthesis was developed to prepare 4-[18F]FEBZA in high radiochemical yields and specific activity. The binding affinity, the in vitro binding, and internalization studies were performed using B16F1 melanoma cell line. The biodistribution studies were performed in C57BL/6 normal mice, C57BL/6 mice bearing B16F1 melanoma tumor xenografts, and nu/nu athymic mice bearing HT-29 human adenocarcinoma tumor and C-32 amelanotic melanoma tumor xenografts. MicroPET studies were performed in mice bearing B16F1 and HT-29 tumor xenografts.Results4-[18F]FEBZA was prepared in 53 ± 14% radiochemical yields and a specific activity of 8.7 ± 1.1 Ci/μmol. The overall synthesis time for 4-[18F]FEBZA was 54 ± 7 min. The in vitro binding to B16F1 cells was 60.03 ± 0.48% after 1 h incubation at 37 °C. The in vivo biodistribution studies show a rapid and high uptake of F-18 in B16F1 tumor with 8.66 ± 1.02%IA/g in this tumor at 1 h. In contrast, the uptake at 1 h in HT-29 colorectal adenocarcinoma and C-32 amelanotic melanoma tumors was significantly lower with 3.68 ± 0.47%IA/g and 3.91 ± 0.23%IA/g in HT-29 and C-32 tumors, respectively. On microPET images, the melanoma tumor was clearly visible by 10 min post-injection and the intensity in the tumor continued to increase with time. In contrast, the HT-29 tumor was not visible on the microPET scans.ConclusionsA rapid and facile synthesis of 4-[18F]FEBZA is developed. This method offers a reliable production of 4-[18F]FEBZA in high radiochemical yields and specific activity. A high binding affinity to melanoma cells and high uptake in tumor was noted. The microPET scan clearly delineates the melanoma tumor by 10 min post-injection. The results from these preclinical studies support the potential of 4-[18F]FEBZA as an effective probe to image melanoma.
Highlights
The purpose of this study was to develop a positron emission tomography (PET) imaging probe that is easy to synthesize and selectively targets melanoma in vivo
The high-performance liquid chromatography (HPLC) column for the purification of 4-[18F]FEBZA was a C-18 reverse-phase, 10 mm × 250 mm, 5-μ Luna column (Phenomenex, Torrence, CA), and elution was performed at a flow rate of 2 mL/min using a solution of methanol:0.1 M ammonium acetate (50:50) containing trimethylamine (40 μL/100 mL)
The total time required for the synthesis, HPLC purification, and reformulation of the final product in buffer required less than 1 h
Summary
The purpose of this study was to develop a positron emission tomography (PET) imaging probe that is easy to synthesize and selectively targets melanoma in vivo. Among many factors, lacking monthly selfinspection of the skin by patients, routine visits to the dermatologist combined with lack of effective diagnostic tools training for the accurate detection of melanoma at an early stage, malignant melanoma remains a significant health problem and remains as the sixth most prevalent type of cancer [1]. Late diagnosis and poor localization of metastatic lesions in patients with melanoma results in high mortality from this cancer [2]. If diagnosed at stage 1 of this disease, the overall 10-year survival for melanoma patients is ~95%. Early diagnosis and accurate assessment of metastatic lesions is crucial for appropriate treatment planning, improved outcome, and disease-free survival [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
