Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma.

Abstract

The imaging potential of a series of [123I]benzamides was studied in mice bearing B16F0 melanoma tumors. Compound [123I]25 exhibited tumor uptake >8 %ID/g at 1 h, while that of [123I]14d and [123I]25 reached a maximum of 9-12 %ID/g at 6 h. Standardized uptake values of [123I]14d were higher than 100 between 24 and 72 h after injection. In haloperidol treated animals, the tumor uptake of [123I]14d was not significantly different to controls, while significant reduction of [123I]25 uptake was observed, supporting that [123I]14d uptake relates to melanin interaction, whereas part of the mechanism of [123I]25 uptake is related to its sigma 1-receptor affinity. Benzamides 14d and 25, which display rapid and high tumor uptake, appear to be promising imaging agents for melanoma detection, while 14d, which displays a long lasting and high melanoma/nontarget ratio, is more suitable for evaluation as a potential radiotherapeutic.

• Authors: Tien Q Pham, Ivan Greguric, Xiang Liu, Paula Berghofer, Patrice Ballantyne, Janette Chapman, Filomena Mattner, Branko Dikic, Timothy Jackson, Christian Loc'h, Andrew Katsifis
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 15 Pg. 3561-72 (Jul 26 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17602544 (Publication Type: Journal Article)

Chemical References

• 4-acetamido-N-(4-(N-butyl-N-methylamino)butyl)-5-iodo-2-methoxybenzamide
• Acetanilides
• Benzamides
• Iodine Radioisotopes
• Ligands
• N-(1-(2-fluoroethyl)piperidin-4-yl)-4-iodobenzamide
• Piperidines
• Radiopharmaceuticals
• Receptors, sigma
• Haloperidol

Topics

• Acetanilides (chemical synthesis, chemistry, pharmacokinetics)
• Animals
• Benzamides (chemical synthesis, chemistry, pharmacokinetics)
• Binding, Competitive
• Haloperidol (pharmacology)
• Iodine Radioisotopes
• Isotope Labeling
• Ligands
• Melanoma, Experimental (diagnostic imaging, metabolism)
• Mice
• Mice, Inbred C57BL
• Piperidines (chemical synthesis, chemistry, pharmacokinetics)
• Radioligand Assay
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Receptors, sigma (antagonists & inhibitors, metabolism)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon
• Transplantation, Heterologous