Amino and iodotamoxifens: synthesis, estrogen receptor affinity and biodistribution

Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol....

Full description

Saved in:
Bibliographic Details
Published inDrug design and delivery Vol. 6; no. 3; p. 195
Main Authors Strickland, L A, Ponce, Y Z, Hunter, D H, Zabel, P L, Powe, J E, Morrissey, G, Driedger, A A, Chamberlain, M J, Tustanoff, E R
Format Journal Article
LanguageEnglish
Published Switzerland 01.09.1990
Subjects
Aged
Animals
Breast Neoplasms - metabolism
Female
Humans
In Vitro Techniques
Iodine Radioisotopes
Isomerism
Lung - metabolism
Mice
Mice, Inbred C3H
Middle Aged
Neoplasms, Experimental - metabolism
Rats
Rats, Inbred Strains
Receptors, Estrogen - metabolism
Sodium Pertechnetate Tc 99m
Tamoxifen - analogs & derivatives
Tamoxifen - metabolism
Tamoxifen - pharmacokinetics
Tissue Distribution
Uterus - drug effects
Uterus - metabolism
Online AccessGet more information

Cover

More Information
Summary:Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol. The four tamoxifen derivatives showed affinities ranging from 50% to 1600% of that of tamoxifen. Under the same conditions, tamoxifen's relative binding affinity was 0.2% of that of estradiol. Preparative routes to the radioiodo-tamoxifens, [131I]-E and Z-1, were also developed and provided approximately 100 MBq of 'no carrier added' material in 40-60% radiochemical yield. Study of the biodistribution of these radioligands in tumor-bearing mice demonstrated significant radioactivity in the tumors and in the uterus. For [131I]-E-1, target to background ratios reached 28 for uterus/blood and 10 for tumor/blood; corresponding optimum ratios for [131I]-Z-1 were 10 and 5. A washout study using estradiol indicated selective uptake in the uterus of Swiss white mice. However, tumor uptake and image contrast in humans following intravenous administration of either [131I]-E or Z-1 were insufficient to allow diagnostic use of the radioiodotamoxifens.
ISSN:0884-2884