Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma

Abstract

Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81 ± 0.82 %ID/g), compared with A375 tumor and inflammation lesion (3.00 ± 0.71 and 1.67 ± 0.56 %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77 ± 0.36 %ID/g at 2 h (versus 1.16 ± 0.23 %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions.

Comparative preclinical evaluation of 68Ga-NODAGA and 68Ga-HBED-CC conjugated procainamide in melanoma imaging

“…These in vivo and ex vivo results correlated well with several studies [8,9,11,28,31] where the biodistribution of other radiolabeled ( 18 F, 68 Ga, 125 I) benzamide derivatives were investigated.…”

“…Considering that this malignancy is associated with high mortality, furthermore the prognosis of patients with metastases is very poor, hence the early detection of small matastatic lesions using highresolution non-invasive imaging techniques (e.g. : PET) is critical in patient survival [11].…”

“…It has been shown that benzamide derivatives (e.g. : procainamide) specifically bind to melanin pigment, therefore several radiolabeled benzamide derivatives have been developed for molecular imaging of melanoma such as 68 Ga-SCN-DOTA-PCA, 68 Ga-SCN-NOTA-BZA [8,9] [11].…”

N-(2-(Dimethylamino)Ethyl)-4-18F-Fluorobenzamide: A Novel Molecular Probe for High-Contrast PET Imaging of Malignant Melanoma

“…Benzamide derivatives for PET comprise radiolabeled benzamide and an aliphatic structure that includes an alkyl linker and an amine residue (11,(21)(22)(23)(24)(25)32,33). Many researchers have modified the structure, especially the benzene ring, to improve radiochemical yield, melanin-targeting ability, or pharmacokinetic properties.…”

4-11C-Methoxy N-(2-Diethylaminoethyl) Benzamide: A Novel Probe to Selectively Target Melanoma

“…Nonetheless, its synthesis takes approximately 3 h and 2 or more purifications (10,11). Recently, several other 18 F-benzamides were evaluated to assess their potential to target melanoma (12)(13)(14)(15). Although the synthesis time of MEL050 (12) and 18 F-FPDA (15) was shorter, the in vitro and in vivo properties of these benzamides were even less optimal than that of 18 F-DAFBA.…”