Fluorine-18-labeled estrogens, progestins and corticosteroids for receptor-based imaging of breast tumors and target areas of the brain

Miscellaneous · Sun Jan 01 00:00:00 EST 1989

OSTI ID:5735117

Pomper, M G

Estrogens can be labeled with the positron-emitting radionuclide fluorine-18 (t{sub 1/2} = 110 min) by fluoride ion (n-Bu{sub 4}N{sup 18}F) displacement of a 16{beta}-trifluoromethanesulfonate (triflate) derivative of the corresponding estrone 3-triflate, and purification by HPLC. That sequence has been used to synthesize the 11{beta}-methoxy 1 and 11{beta}-ethyl 2 analogues of the breast tumor imaging agent, 16{alpha}-({sup 18}F)fluoro-17{beta}-estradiol (FES). Tissue distribution studies of 1 and 2 in immature female rats show high selectivity for target tissue (T, uterus) vs non-target (NT, muscle and lung), with T/NT ratios being 43 and 17 at one hour after injection for 1 and 2, respectively. The parent estrogen FES has previously been shown to display an intermediate value for tissue selectivity. The progestin 21-({sup 18}F) fluoro-16{alpha}-ethyl-19-nor progesterone (FENP), synthesized from the 21-triflate precursor, is a high affinity ligand for the progestin receptor, and in vivo, exhibits highly selective uptake by the uterus of estrogen-primed rats. Respective T/NT ratios of 16 and 41 at one and 3 hours after injection have been demonstrated. Two epimeric (at C-21) analogues of the high affinity progestin promegestone (R 5020) were prepared in fluorine-18 labeled form from the corresponding triflate precursors; while 21S-({sup 18}F)R 5020 3 showed a T/NT ratio of 4 at 3 hours after injection, 21R-({sup 18}F)R 5020 4 showed no selective uptake. Compounds 3 and 4 each suffered extensive in vivo defluorination. Derivatives of the high affinity Type I and Type II corticosteroid receptor ligands RU 26752 and RU 28362, respectively, were prepared in fluorine-18 labeled form from the corresponding 3{prime}-methanesulfonates. Neither labeled compound showed selective target tissue (brain) uptake and each underwent substantial in vivo defluorination.

• Research Organization: Illinois Univ., Urbana, IL (USA)
• OSTI ID: 5735117
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
MAMMARY GLANDS
POSITRON COMPUTED TOMOGRAPHY
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
CORTICOSTEROIDS
ESTROGENS
FLUORINE 18
LIGANDS
LIQUID COLUMN CHROMATOGRAPHY
PROGESTERONE
ADRENAL HORMONES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE ISOTOPES
GLANDS
HORMONES
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KETONES
LABELLED COMPOUNDS
LIGHT NUCLEI
NANOSEC LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PREGNANES
RADIOISOTOPES
SEPARATION PROCESSES
STEROID HORMONES
STEROIDS
SYNTHESIS
TOMOGRAPHY
550601* - Medicine- Unsealed Radionuclides in Diagnostics