D. Parry

Synthesis, radiolabeling, and preliminary evaluation in mice of some (N-Diethylaminoethyl)-4-iodobenzamide derivatives as melanoma imaging agents

N-(2-Diethylaminoethyl)-4-iodobenzamide (BZA) is a radiopharmaceutical recently developed in our laboratory for the scintigraphic detection of melanoma and metastases. Optimal time for imaging was between 18-24 h p.i. of [123I] BZA. With a view to selecting compounds able to provide quality images shortly after the injection, synthesis of an initial series of BZA derivatives and their evaluation in B16 melanoma bearing mice have been carried out. The [125I] radiolabeled products were obtained by a simple isotopic exchange procedure with high radiochemical yields (85-95%). After i.v. administration of the compounds we observed a good tumoral targeting ability. Tumoral activity peaked at 2.6 to 7.70% injected dose per g within 1 h post-injection. One of the benzamides with a blood clearance faster than that of BZA--0.06 vs. 0.2% I D/g--6 h p.i. gave the same tumor to blood and to organ ratios as BZA at 12-18 h p.i. Based on these preclinical data we hope to obtain good tumoral images 6 h p.i. in scintigraphic studies in man.

Disposition in rats and mice of 7-methoxy-2-nitronaphtho[2,1-b]furan

The disposition of 7-methoxy-2-nitronaphtho[2,1-b]furan (MNNF), labelled with 14C in the furan ring (label 1) and in the methoxy group (label 2) has been studied in rats and mice. After i.p. administration to rat (5 mg/kg), both labelled species were absorbed by the lymphatics; and after oral administration, through the intestinal lumen. Excretion of the furan ring (label 1) is mainly urinary (44% dose in 24 h); label 2 was mostly expired as 14CO2 (48% dose in 24 h), indicating considerable demethylation. No target organ was found for MNNF, except liver and kidney. For both labelled species given orally, radioactivity was bound to the intestinal wall. Preliminary metabolic studies, using t.l.c. and h.p.l.c., have shown the presence of an urinary metabolite, namely, the glucuronide of 7-hydroxy-2-nitronaphtho[2,1-b]furan (15-20% of the urinary radioactivity). The remaining radioactivity comprises basic compounds, that bind to a cationic resin, which might be formed by enzymic reduction of the nitro group.

A boronated benzamide as melanoma-seeking agent

Abstract A boronated benzamide which accumulates in melanin-rich tissues in mice is presented.

Main excretion metabolites of 7-methoxy-2-nitronaphtho[2,1-b]furan (R 7000) in rats.

Major metabolites, isolated from rat bile and urine after administration of a single dose of 7-methoxy-2-nitronaphtho[2,1-b]furan (R 7000; MNNF) labelled with 14C on the furan ring and on the methoxy group, were identified by comparison of their chromatographic behaviour and mass spectra with synthetic authentic reference compounds. Analysis of metabolites indicated three metabolic pathways for this compound in vivo, namely, demethylation of the methoxy group, hydroxylation of the aromatic ring and cleavage of the furan ring, followed by the reduction of the nitro group to amine.