Linked Life Data

8487253

Source:http://linkedlifedata.com/resource/pubmed/id/8487253

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1993-6-9
pubmed:abstractText
We have studied two new fluorine-substituted progestins as potential imaging agents for progesterone-receptor-positive human breast tumors. The steroids are 16 alpha, 17 alpha-fluoroacetophenone ketals of 16 alpha, 17 alpha-dihydroxyprogesterone and 16 alpha, 17 alpha, 21-trihydroxy-19-norprogesterone. Synthesis of the latter compound in seven steps from 19-norandrost-4-ene-3,17-dione is reported. Both compounds demonstrate high affinity for the progesterone receptor (PgR) (52.5 and 240%, respectively, relative to R5020 = 100). The syntheses were adapted to 18F-labeling with 4'-[18F]-fluoroacetophenone, prepared from 4'-nitroacetophenone by nucleophilic substitution with K18F/Kryptofix. Considerable adjustment of reaction conditions was required to effect ketalization using tracer quantities of the ketone. In tissue distribution studies in estrogen-primed immature female rats, both ketals showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Additionally, metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. Both compounds showed relatively high uptake in fat, in accord with their relative lipophilicities demonstrated by HPLC-derived octanol-water partition coefficients. The selective uterine uptake and metabolic stability of these compounds suggests that this class of PgR ligands might be promising for the selective imaging of receptor-positive tumors if derivatives of reduced lipophilicity can be prepared.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1120-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Fluorine-18-labeled progestin ketals: synthesis and target tissue uptake selectivity of potential imaging agents for receptor-positive breast tumors.
pubmed:affiliation
Department of Chemistry, University of Illinois, Urbana 61801.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't