Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma

Tien Q Pham; Ivan Greguric; Xiang Liu; Paula Berghofer; Patrice Ballantyne; Janette Chapman; Filomena Mattner; Branko Dikic; Timothy Jackson; Christian Loc'h; Andrew Katsifis

doi:10.1021/jm0701627

Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma

J Med Chem. 2007 Jul 26;50(15):3561-72. doi: 10.1021/jm0701627. Epub 2007 Jun 28.

Authors

Tien Q Pham¹, Ivan Greguric, Xiang Liu, Paula Berghofer, Patrice Ballantyne, Janette Chapman, Filomena Mattner, Branko Dikic, Timothy Jackson, Christian Loc'h, Andrew Katsifis

Affiliation

¹ Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, PMB 1 Menai N.S.W. 2234, Sydney, Australia.

PMID: 17602544
DOI: 10.1021/jm0701627

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.

MeSH terms

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

Substances

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