Evaluation of Radiolabeled (Hetero)Aromatic Analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for Imaging and Targeted Radionuclide Therapy of Melanoma

Abstract

Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4-iodobenzamide (BZA) are of interest. Various (hetero)aromatic analogues 5 of BZA were synthesized and radioiodinated with (125)I, and their biodistribution in melanoma-bearing mice was studied after i.v. administration. Most [ (125)I] 5-labeled compounds appeared to bind specifically and with moderate-to-high affinity to melanoma tumor. Two compounds, 5h and 5k, stood out with high specific and long-lasting uptake in the tumor, with a 7- and 16-fold higher value than BZA at 72 h, respectively, and kinetic profiles that makes them promising agents for internal targeted radionuclide therapy of melanoma.

High-Contrast PET of Melanoma Using 18F-MEL050, a Selective Probe for Melanin with Predominantly Renal Clearance

“…In recent years, several other radiolabeled imaging probes have been evaluated for melanoma imaging, including methylene blue dye (10), monoclonal antibodies against melanoma-associated antigens (11,12), iodoamphetamine (13), a-melanocyte-stimulating hormone ana-logs (14,15), and benzamide (BZA)-based compounds (16,17). To date, iodinated BZA analogs have been among the most promising of the newer melanoma radiotracers for both diagnosis and therapeutic applications.…”

Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies

“…Among the numerous strategies aimed at increasing intarget drug accumulation, "vectors" with high specific affinities for one or more targets offer one of the most promising therapeutic opportunities [4]. Our team has built up recognized expertise in vectorization strategies through work identifying chemical carriers able to selectively deliver radionuclides and drugs to tissues for targeted imaging and therapy [5,6]. Our chondrosarcoma management-oriented strategy is to exploit the chondrogenic nature of the tumour in order to selectively deliver drugs or radioisotopes to tumoural tissue.…”

Preclinical investigation of tolerance and antitumour activity of new fluorodeoxyglucose-coupled chlorambucil alkylating agents

“…For many years, our group has been recognized for its expertise in vectorization strategies, through its work on identifying chemical carriers able to deliver radiopharmaceuticals and drugs selectively to tissues for targeted imaging and therapy respectively [4][5][6]. Our previous work has shown in particular that imaging agents and drugs can be targeted towards certain biochemical and phenotypical tumour features, e.g.…”