Synthesis and biological evaluation of fluorine-18-labeled estrogens and progestins as positron emission tomography (PET) imaging agents

Thesis/Dissertation · Mon Jan 01 04:00:00 EST 1990

OSTI ID:7013964

VanBrocklin, H F

Seven new estrogen receptor-based radiopharmaceuticals, 16[alpha]-[[sup 18]F]-fluoro-17[alpha]-ethynyl-estradiol, (FEES), 15, 11[beta]-methoxy-FEES, 16, 11[beta]-ethyl-FEES, 17, 16[beta]-[[sup 18]F]-fluoroestradiol, (16[beta]-FES), 19, 11[beta]-methoxy-16[beta]-FES, 20, 16[beta]-[[sup 18]F]-fluoro-17[alpha]-ethynyl-estradiol, (16[beta]FEES), 21, and 11[beta]-methoxy-16[beta]-FEES, 22, have been prepared and evaluated as potential PET imaging agents for estrogen receptor-rich breast tumors. Radiolabeling was achieved by nucleophilic displacement of the appropriate 16[beta]- or 16[alpha]-trifluoromethanesulfonate(triflate)-estrone-3-triflate derivative with nBu[sub 4]N[sup 18]F. Subsequent hydride reduction or nucleophilic attack by lithium-trimethylsilylacetylide followed by HPLC purification yielded the FES or FEES analogs, respectively. These compounds can be prepared in 90-120 minutes from [sup 18]F-fluoride with radiochemical yields of 1-40% (decay corrected) and effective specific activities ranging from 50-4,000 Ci/mmol. The relative binding affinities (RBA) ranged from 0.5 to 309. Biological distribution was performed in 25 day old Sprague-Dawley female rats. Uterine uptake ranged from 5-16 percent of the injected dose. These fluorestrogens were highly selective in vivo as evidenced by the high uterus-to-blood (range 10-170) and uterus-to-muscle (range 25-80) ratios. The FEES analogs, 15,16, and 17, had the highest uterus to blood ratios ever seen amongst estrogen radiopharmaceuticals; 154, 145 and 169, respectively. The dose to critical clearance organs (liver and kidneys) was less than 3% of the injected dose per gram of tissue. Metabolic defluorination did not occur with these compounds. These new analogs exhibited an array of desirable characteristics for the optimal PET imaging of estrogen receptor-positive human mammary tumors.

• Research Organization: Washington Univ., Seattle, WA (United States)
• OSTI ID: 7013964
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CHEMICAL PREPARATION
COMPARATIVE EVALUATIONS
COMPUTERIZED TOMOGRAPHY
DATA
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
ESTROGENS
EVALUATION
EXPERIMENTAL DATA
FEMALE GENITALS
FLUORINE 18
FLUORINE COMPOUNDS
FLUORINE ISOTOPES
GLANDS
HALOGEN COMPOUNDS
HORMONES
HOURS LIVING RADIOISOTOPES
INFORMATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KETONES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MAMMARY GLANDS
MEMBRANE PROTEINS
METABOLISM
NANOSEC LIVING RADIOISOTOPES
NEOPLASMS
NUCLEI
NUMERICAL DATA
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PREGNANES
PROGESTERONE
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
RECEPTORS
RODENTS
STEROID HORMONES
STEROIDS
SYNTHESIS
TOMOGRAPHY
UPTAKE
UTERUS
VERTEBRATES