Uptake In Uterus Research Articles

Physiological tracer distribution and benign lesion incidental uptake of Al18F-NOTA-FAPI-04 on PET/CT imaging.

To systematically investigate the physiological distribution and benign lesion incidental uptake of Al18F-NOTA-FAPI-04 (18F-FAPI) in cancer patients to establish the normal uptake range in relevant organs and lesions. Twenty patients who underwent 18F-FAPI PET/CT imaging were retrospectively assessed. Organ and benign lesion tracer uptake was quantified based on standardized uptake values (SUVmax and SUVmean). We compared the variation in tracer uptake in certain organs between men and women, analyzed the possible reasons for diffuse uptake in the thyroid, and assessed tracer uptake variations in the uterus in different menstrual cycle phases. Incidental tracer uptake in benign lesions was also assessed. Physiological 18F-FAPI uptake was observed in the urinary tract, biliary tract system, submandibular glands, pancreas, thyroid, uterus, intestine, prostate gland, parotid gland, myocardium, kidney cortex, and muscles, but not the brain, lungs, liver, spleen, colon, and breasts. The SUVmean for each organ was similar for women and men (all P > 0.05). Diffuse tracer uptake in the thyroid was caused by normal thyroid or thyroiditis; there were no statistically significant differences between them (SUVmax: t = -1.3, P = 0.25; SUVmean: t = -1.1, P = 0.31). There was a significant difference for uterus uptake among different menstrual cycle phases (SUVmax: F = 5.08, P = 0.04; SUVmean: F = 5.19, P = 0.04). Incidental benign lesion tracer uptake was observed in patients with esophagitis, thyroiditis, arthritis, fractures, and uterine fibroids. This study provides a reference range for 18F-FAPI uptake in relevant organs and benign lesions. Benign lesion 18F-FAPI uptake may reduce 18F-FAPI PET/CT specificity.

18F–labeled estradiol derivative for targeting estrogen receptor-expressing breast cancer

IntroductionA novel radiotracer 1‑(2‑(2‑(2‑[18F]fluoroethoxy)ethoxy)ethyl)‑1H‑1,2,3‑triazole‑estradiol ([18F]FETE) was successfully synthesized, characterized and evaluated in mice for estrogen receptor (ER)-positive breast cancer targeting with positron emission tomography (PET) imaging. MethodsThe tosylate precursor 3 was radiolabeled with 18F and then reacted with 17α‑ethinyl‑estradiol to produce the final [18F]FETE. The physicochemical properties of [18F]FETE were tested in vitro, including determination of the octanol/water partition coefficient, stability and cellular uptake in MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) cells. An ex vivo biodistribution study was performed in normal Sprague Dawley rats, and in vivo microPET imaging was performed on MCF-7 and MDA-MB-231 tumor-bearing mice. The results of biodistribution and PET imaging of [18F]FETE were compared with that of known 16α‑[18F]fuoro‑17β‑estradiol ([18F]FES). Radiation dose estimates for [18F]FETE were also analyzed. Results[18F]FETE was obtained in high radiochemical yield (46.59 ± 8.06%) with high radiochemical purity (>99%) after HPLC purification and high molar activity (15.45 ± 3.15 GBq/μmol). [18F]FETE is a moderate lipophilic compound with good in vitro stability and the total synthesis time was 55 to 65 min. In biodistribution studies, [18F]FETE showed high uptake in the ER-abundant uterine tissue of normal immature SD rats (8.55 ± 1.21 and 6.83 ± 1.70%ID/g at 1 h after intravenous and intraperitoneal injection, respectively), and could be blocked with estradiol effectively (the uterus uptake was decreased to 0.63 ± 0.35%ID/g at 1 h after iv injection). MicroPET imaging of tumor-bearing mice with [18F]FETE at 1 h after iv injection revealed considerable uptake in ER-positive MCF-7 tumors (4.63 ± 0.73%ID/g) that could be inhibited (1.47 ± 0.29%ID/g) and low uptake in ER-negative MDA-MB-231 tumors (1.97 ± 0.36%ID/g). [18F]FES has relatively low uptake in ER-positive tumor (0.24 ± 0.19%ID/g) when compared with [18F]FETE. The adult female effective radiation dose of [18F]FETE in mice was estimated as 0.0022 mSv/MBq. ConclusionsA novel 17α‑ethinyl‑estradiol-based ER probe [18F]FETE was developed with high molar activity and good in vitro stability. Based on the results of bio-evaluation in normal immature rats and tumor-bearing mice, it might be a promising candidate for specific PET imaging of ER-positive breast cancer.

Optimization of the alkyl side chain length of fluorine-18-labeled 7α-alkyl-fluoroestradiol

IntroductionSeveral lines of evidence suggest that 7α-substituted estradiol derivatives bind to the estrogen receptor (ER). In line with this hypothesis, we designed and synthesized 18F-labeled 7α-fluoroalkylestradiol (Cn-7α-[18F]FES) derivatives as molecular probes for visualizing ERs. Previously, we successfully synthesized 7α-(3-[18F]fluoropropyl)estradiol (C3-7α-[18F]FES) and showed promising results for quantification of ER density in vivo, although extensive metabolism was observed in rodents. Therefore, optimization of the alkyl side chain length is needed to obtain suitable radioligands based on Cn-7α-substituted estradiol pharmacophores. MethodsWe synthesized fluoromethyl (23; C1-7α-[18F]FES) to fluorohexyl (26; C6-7α-[18F]FES) derivatives, except fluoropropyl (C3-7α-[18F]FES) and fluoropentyl derivatives (C5-7α-[18F]FES), which have been previously synthesized. In vitro binding to the α-subtype (ERα) isoform of ERs and in vivo biodistribution studies in mature female mice were carried out. ResultsThe in vitro IC50 value of Cn-7α-FES tended to gradually decrease depending on the alkyl side chain length. C1-7α-[18F]FES (23) showed the highest uptake in ER-rich tissues such as the uterus. Uterus uptake also gradually decreased depending on the alkyl side chain length. As a result, in vivo uterus uptake reflected the in vitro ERα affinity of each compound. Bone uptake, which indicates de-fluorination, was marked in 7α-(2-[18F]fluoroethyl)estradiol (C2-7α-[18F]FES) (24) and 7α-(4-[18F]fluorobutyl)estradiol (C4-7α-[18F]FES) (25) derivatives. However, C1-7α-[18F]FES (23) and C6-7α-[18F]FES (26) showed limited uptake in bone. As a result, in vivo bone uptake (de-fluorination) showed a bell-shaped pattern, depending on the alkyl side chain length. C1-7α-[18F]FES (23) showed the same levels of uptake in uterus and bone compared with those of 16α-[18F]fluoro-17β-estradiol. ConclusionsThe optimal alkyl side chain length of 18F-labeled 7α-fluoroalkylestradiol was the shortest: C1-7α-[18F]FES. Our results indicate that shorter chain lengths within the 4-Å ligand binding cavities of ERα are suitable for 7α-fluoroalkylestradiol derivatives.

In vitro evaluation, biodistribution in rats of radiolabeled raloxifene

Raloxifene is a selective estrogen receptor modulator that produces both estrogen agonistic effects on bone and lipid metabolism and estrogen-antagonistic effects on uterine endometrium and breast tissue. In the present study, raloxifene was labeled with I-131 by iodogen method and investigated for its radiopharmaceutical potential. Radiolabeling yield is 91±0.7%, as determined by radio thin layer chromatography (RTLC). Results of in vitro study indicated 131I-raloxifene has high stability (4 h) in serum. Biodistribution study was carried out with Albino wistar female rats. The result has shown that the radioiodinated raloxifene has higher uptake in uterus than breast and ovarian.

Assessment of Human Biodistribution and Dosimetry of 4-Fluoro-11β-Methoxy-16α-18F-Fluoroestradiol Using Serial Whole-Body PET/CT

4-Fluoro-11beta-methoxy-16alpha-18F-fluoroestradiol (4FMFES) is a newly developed radiolabeled estradiol analog for PET imaging of estrogen receptors (ERs) that shows improved target-to-background ratios, compared with 16alpha-18F-fluoroestradiol (FES), in small-animal models. The aim of this study was to assess the biodistribution, dosimetry, and safety of 4FMFES in healthy women. Ten healthy subjects (6 pre- and 4 postmenopausal women) who had fasted were injected with 66-201 MBq of 4FMFES at a high effective specific activity (median, 251 GBq/micromol). During a 2-h period, each subject underwent 4 serial rapid PET acquisitions and 2 low-dose CT acquisitions on a PET/CT camera. Volumes of interest were drawn over source organs for each PET acquisition, allowing the calculation of time-activity curves, residence times, and radiation dosimetry estimates. Serial blood samples were obtained to measure blood and plasma activity clearance. 4FMFES safety was assessed by blood and urine analyses and vital-sign monitoring. A 4FMFES injection was well tolerated in all subjects. The liver showed high uptake, and the hepatobiliary excretion was massive. Little urinary excretion occurred. Uterus uptake was visualized in all subjects and remained relatively constant over time (maximum and mean standardized uptake values at 60 min were 5.34+/-3.32 and 2.68+/-1.89, respectively). Background activity was low and decreased over time, resulting in an increasing uterus-to-background ratio (12.1+/-2.2 at 60 min). The critical organ was the gallbladder (0.80+/-0.51 mGy/MBq), followed by the upper large intestine (0.13+/-0.04 mGy/MBq), small intestine (0.12+/-0.04 mGy/MBq), and liver (0095+/-0.019 mGy/MBq). For a typical 4FMFES dose of 185 MBq, the effective dose was calculated at 4.82+/-0.70 mSv. 4FMFES is considered safe for use in humans, and its effective dose remains well within acceptable limits. The absorbed dose to the gallbladder was relatively high and could potentially be reduced by injecting 4FMFES in patients who had not fasted. 4FMFES showed a significant, potentially estrogen receptor-mediated uterus uptake in both pre- and postmenopausal subjects.

Utility of [18F] fluoro-2-deoxy-d-glucose positron emission tomography in the localization of ectopic ACTH-secreting tumors

Ectopically ACTH producing tumors may be difficult to localize by conventional radiology and functional imaging may be helpful. Case 1: 31-year-old man was diagnosed with ectopic ACTH-dependent Cushing's syndrome (ECS). Thorax CT revealed a 1.3 cm nodular opacity in upper left lobe, suggestive of residual lesion. [(18)F] fluoro-2-deoxy-D: -glucose ([(18)F] FDG) positron emission tomography ([(18)F] FDG PET) scan revealed mild glycolytic metabolic activity. Pathological examination confirmed an ACTH-positive carcinoid tumor. Case 2: 53-year-old woman presented with very rapid onset ECS. Pituitary MRI was normal. Thorax CT revealed no tumoral lesion. Abdominal and pelvic MRI showed images suggestive of hepatic and iliac, femoral and lumbar secondary implants. [(18)F] FDG PET scan revealed intense uptake in uterus, especially cervix, suggesting this to be the primary tumor site. These cases illustrate the role of [(18)F] FDG PET in the investigation of an ECS where conventional imaging studies were not elucidative in the search for a responsible tumor.

Impact on estrogen receptor binding and target tissue uptake of [ 18F]fluorine substitution at the 16α-position of fulvestrant (faslodex; ICI 182,780)

Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16α-[ 18F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ERα and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for 18F would have led to a product of low specific activity; instead we selected the 16α-position for 18F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [ 18F]fluoride at the 16- 18F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or sulfoxide (fulvestrant) were prepared. Introduction of the 16 18F-fluorine led to a dramatic decrease of the apparent binding affinity for ER, as reported by Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated uterus uptake values in immature female rats were disappointing. Overall, our findings suggest that these new PET radiopharmaceuticals are not suitable as tracers to predict ER(+) breast cancer response to hormonal therapy with selective ER modulators.

Synthesis and biological properties of 7α-cyano derivatives of the (17α,20 E/Z)-[ 125I]iodovinyl- and 16α-[ 125I]iodo-estradiols

The synthesis, receptor binding affinity, estrogenic potency and tissue distribution of the 7α-cyano derivatives of the (17α,20 E/Z)-[ 125 I ]iodovinyl-(CIVE) and 16α-[ 125 I ]iodo-estradiols (CIE) are reported. The iodovinyl derivatives were prepared via the (17α,20 E/Z)-tri- n-butylstannyl intermediates, derived from the addition of tri- n-butyl tin hydride to the 17α-ethynyl group of the 7α-cyano-17α-ethynylestradiol, using triethylborane as a catalyst. The no-carrier-added [ 125 I ]-CIVE isomers were prepared via the same stereospecific reaction. [ 125 I ]-CIE was prepared from 7α-cyano-16β-bromoestradiol via halogen exchange with Na 125 I . Addition of the 7α-cyano group to 16α-iodoestradiol did not affect estrogen receptor binding affinity (RBA of CIE is 115). However the estrogenic potential of CIE, as measured by the capacity to stimulate the expression of the pS2 gene, was reduced to 1% as compared to that of estradiol. Addition of a 7α-cyano group to the (17α,20 E/Z)-IVE isomers reduced the RBA to 21 and 36, respectively, while the estrogenic potential was reduced to 2–3% of that of estradiol. Uterus uptake in immature rats of the 125 I -labeled CIVE 20 E-isomer and the 16α-iodo CIE peaked at 0.5 h post injection while the (17α,20 Z)-CIVE isomer showed a maximum only past 5 h post injection. Uptake of all three 125 I -labeled 7α-cyanoestrogens was suppressed by the co-injection of non-radioactive estradiol confirming the role of estrogen receptors in the localization process. Uterus retention pattern differ substantially from those of the analogues 7α-methylestrogens, which were previously shown to give high maximum 125 I -uptake values at 2 h post injection. Overall our data indicate that addition of a 7α-cyano group to 123 I -labeled estrogens does not improve their potential to serve as SPECT agents for the imaging of estrogen receptor densities in breast cancer.

Synthesis of the 7α-cyano-(17α,20 E/ Z)-[ [formula omitted]]iodovinyl-19-nortestosterones: potential radioligands for androgen and progesterone receptors

We report the preparation of the 7α-cyano derivative of the isomeric (17α,20 E/ Z)-[ 125 I ]iodovinyl-19-nortestosterones (IVNT) together with their binding affinity for the androgen receptor (AR) and their biodistribution in two different animal models. The cyano group was introduced at the 7α-position by hydrocyanation of 4,6-estradien-17β-ol-3-one with diethylaluminum cyanide. Selective protection of the A-ring enone system as the dienol ether followed by ethynylation and deprotection under base and acid hydrolysis condition gave 7α-cyano-17α-ethynyl-19-nortestosterone. The stannyl derivatives were prepared by addition of tri- n-butylstannyl hydride and converted stereospecifically to the corresponding [ 125 I ]iodovinyl analog using [ 125 I ]NaI and H 2O 2. The [ 125 I ]iodovinylsteroids were intravenously administered to male rats and estrogen-primed immature female rats and tissue uptake was measured up to 6 h post-injection. Co-administration of NLP-004 or ORG-2058, highly selective ligands for the progesterone receptor, to the female rats did not affect uterus uptake of the 125 I -ligands. However co-injection of testosterone to DES-primed male rats induced a marked increase in prostate uptake of the 20 Z-isomer of 7α-cyano-[ 125 I ]-IVNT. The relative binding affinity (RBA) of either 7α-cyano-(17α,20 E/ Z)-IVNT isomer for the AR is low (RBA=4 and 3, respectively, versus 100 for 5α-dihydrotestosterone (DHT)), suggesting the absence of a possible role of the AR in the localization process. These findings contrast previously reported data for the analogous 7α-methyl-[ 125 I ]-IVNT where co-administration of testosterone was shown to result in a 50% drop in prostate uptake. These data indicate that the addition of an electron withdrawing 7α-cyano group to 123 I -labeled nortestosterone derivatives does not improve their potential to serve as SPECT agents for the imaging of AR densities in the prostate.

Progestin radiopharmaceuticals labeled with technetium and rhenium: synthesis, binding affinity, and in vivo distribution of a new progestin N2S2-metal conjugate.

We have prepared and evaluated three metal conjugates of a progestin-monoamine-monoamide (MAMA') bisthiol chelate system. These conjugates of rhenium and technetium-99 and -99m, are structural analogs of the bisamino-bisthiol (BAT) conjugates we have described recently, but the MAMA' chelate, being more polar than the BAT system, gives a conjugate that is much less lipophilic, having an octanol-water partition coefficient that is nearly 80-fold lower. In competitive binding assays, the Re- and 99Tc-MAMA'-progestin conjugates bind to the progesterone receptor with affinities greater than that of progesterone itself, and in a direct binding assay, the equilibrium dissociation constant (Kd) of the 99mTc-MAMA' conjugate was 0.97 nM. As is typical for 11 beta-substituted progestins, these conjugates also have substantial binding affinity for glucocorticoid receptors. In tissue distribution studies in immature female rats, the progestin-99mTc-MAMA' conjugates show selective uptake for principal target tissue (such as uterus) over that of blood and nontarget tissue (such as muscle); these uptake ratios reach maximum levels of 5 and 4, respectively. Uptake by fat, liver, and kidney is quite high; however, only the uptake in uterus is displaceable upon coinjection of the selective progestin ORG2058. Metabolism studies show that the radioactivity in the uterus is essentially unmetabolized out to 4 h, while liver activity is completely due to metabolites. Other tissues show an intermediate fraction of unmetabolized conjugates that decreases with time. The in vivo behavior of the progestin-99mTc-MAMA' conjugate is similar to that of the labeled BAT conjugate: its uptake selectivity is somewhat greater than that of the BAT conjugate, but its target tissue uptake is lower. Factors that may be responsible for limiting the target tissue uptake properties of these conjugates are their moderate affinity for progesterone receptor, their substantial binding to glucorticoid receptors, and their large overall molecular size.

Imaging, biodistribution and therapy potential of Halogenated tamoxifen analogues

Tamoxifen binds to estrogen receptors (ERs) and prevents breast cancer cell proliferation. This study is aimed at developing a ligand for imaging ER (+) breast tumors by positron emission tomography (PET) or single photon emission computed tomography (SPECT). [ 18F]-Labeled tamoxifen analogue ([ 18F]FTX) was prepared in 30–40% yield and [ 131I]-labeled tamoxifen analogue ([ 131I]ITX) was prepared in 20–25% yield. In mammary tumor-bearing rats, the biodistribution of [ 18F]FTX at 2 h showed a tumor uptake value (% injected dose/gram tissue) of 0.41 ± 0.07; when rats were pretreated with diethylstilbestrol (DES), the value changed to 0.24 ± 0.017. [ 131]ITX at 6 h showed a tumor uptake value of 0.26 ± 0.166; when rats were pretreated with DES, the value changed to 0.22 ± 0.044. Priming tumor-bearing rats with estradiol, a tumor uptake value for [ 131]ITX was increased to 0.48±0.107 at 6 h. In the [ 3H]estradiol receptor assay, tumors had a mean estrogen receptor density of 7.5 fmol/mg of protein. In gamma scintigraphic imaging studies with [ 131I]ITX, the rabbit uterus uptake can be blocked by pretreatment with DES. Both iodotamoxifen and tamoxifen reduced ER(+) breast tumor growth at the dose of 50 μg in tumor-bearing mice. The findings indicate that tamoxifen analogue uptake in tumors occurs via an ER-mediated process. Both analogues should have potential for diagnosing functioning ER(+) breast cancer.

Synthesis of A-ring fluorinated derivatives of (17 alpha,20E/Z)-[125I]iodovinylestradiols: effect on receptor binding and receptor-mediated target tissue uptake.

We have prepared a series of 2- and 4-fluoro derivatives of the isomeric (17 alpha,20E)- and (17 alpha, 20Z)iodovinylestradiols (IVE2) and also the analogs substituted with either a 7 alpha-methyl (7 alpha-Me-IVE2) or 11 beta-methoxy group (11 beta-OMe-IVE2) and evaluated their in vitro and in vivo properties. Electrophilic substitution of the estrone derivatives with N-fluoropyridinium salt gave the 2- and 4-fluoro analogs which were subsequently converted to the 17 alpha-ethynyl derivatives. The tributylstannyl intermediates were obtained from the corresponding 17 alpha-ethynyl analogs using azobisisobutyronitrile or triethylborane as catalyst. All 12 products were also prepared as their no-carrier-added [125I]iodovinyl analogs via destannylation of the tributylstannyl precursors. Binding affinity for the estrogen receptor (ER) was in general higher for the 4-F derivatives as compared to the 2-F derivatives, while the 20Z isomers of the same compounds showed somewhat higher ER binding affinity as compared to the 20E isomers. The combination of an A-ring fluoro and 7 alpha- or 11 beta-substituent decreased ER binding affinity. Substitution of a fluoro atom at C-4 on either the 17 alpha-ethynylestradiol or isomeric 17 alpha-IVE2 enhanced the affinity of the parent molecule for the ER. A-ring fluorination of all other analogues tested had no effect or depressed ER binding affinity. Varying incubation conditions showed substantial differences in ER binding kinetics between the 20E and 20Z isomers. Tissue distribution in immature female rats showed that the highest uterus uptake and uterus to blood/nontarget ratios in the IVE2 series were obtained with the 4-F-(17 alpha,20Z)IVE2 isomer. The combination of A-ring fluoro and 7 alpha- or 11 beta-substitution decreased uterus uptake but had little or no effect on uterus to blood/nontarget ratios. The highest uterus to blood ratios were observed for the 4-F-(17 alpha,20E)11 beta-OMe-IVE2 (75 at 6 h and 125 at 12 h pi) reflecting rapid blood clearance and in vivo stability, as confirmed by the low levels of thyroid radioactivity. The lack of correlation between ER binding affinities and uterus uptake, and/or uptake ratios, suggests that other factors, including nonspecific binding and metabolic processes, also are involved in the tissue localization process. Our data suggest that 4-F substitution onto (17 alpha,20Z)IVE2 and (17 alpha,20E)11 beta-OMe-IVE2 enhances the potential of these compounds to function as SPECT imaging agents of ER-rich tissues.

Uptake of relaxin in the uterus and cervix of rats in vivo: influence of ovarian steroids and tolerance.

The influence of oestradiol benzoate and progesterone treatment and of tolerance to relaxin on the uptake of 125I-labelled porcine relaxin by reproductive tissues was investigated in anaesthetized female rats. In ovary-intact rats, 125I-labelled relaxin uptake increased with time in reproductive tissues and in tissues concerned with metabolism and excretion. Administration of 50 micrograms unlabelled porcine relaxin before injection of 125I-labelled relaxin significantly reduced uptake of 125I-labelled relaxin into the uterus and cervix, but had no effect on uptake of 125I-labelled relaxin into other tissues, indicating that specific uptake of relaxin was occurring in the uterus and cervix. In ovariectomized rats, treatment with oestradiol benzoate or oestradiol benzoate plus progesterone for 1 day did not significantly increase uterine or cervical 125I-labelled relaxin uptake compared with corn oil-treated rats, but induced a significant increase in uterine uptake of 125I-labelled relaxin after treatment for 2 days. Induction of tolerance to relaxin by i.v. infusion of a high dose of relaxin significantly reduced uterine and cervical uptake of 125I-labelled relaxin at 3 h after termination of infusion compared with saline-infused rats. By 12 h after termination of infusion, 125I-labelled relaxin uptake in the uterus and cervix was similar in saline-infused rats and in rats given an infusion of relaxin. Infusion of glibenclamide (20 mg kg-1) did not influence uterine or cervical uptake of 125I-labelled relaxin; however, treatment with phentolamine (10 mg kg-1) significantly reduced 125I-labelled relaxin uptake in uterus, bladder and jejunum. This study demonstrates that steroid hormone treatment and tolerance modulate relaxin uptake in reproductive tissues.

ChemInform Abstract: SYNTHESIS, RECEPTOR BINDING, AND TARGET‐TISSUE UPTAKE OF CARBON‐11 LABELED CARBAMATE DERIVATIVES OF ESTRADIOL AND HEXESTROL

AbstractDurch Umsetzung der Amine (I) und (VII) mit Chlorameisensäureethylester (II) erhält man die Carbamate (III) bzw. (VIII).

UPTAKE OF RADIOACTIVE OESTRADIOL IN SOME ORGANS OF IMMATURE MICE.

ABSTRACT The uptake of radioactivity in some organs after the injection of oestradiol-3H to immature mice has been studied. The uterus and vagina contained more radioactivity per unit wet weight than skeletal muscle, for at least 15 hours. The uptake in the uterus and vagina could be inhibited by carrier oestradiol at a dose level of about 0.3 μg. Oestradiol accumulated by the uterus and vagina could not be easily displaced by a second injection of oestradiol. Oestrogen-stimulated uteri and vaginae retained their capacity to take up oestradiol. The structure specificity of the uptake was demonstrated by the two 17-OH isomers of oestradiol. 17β-oestradiol was more uterotrophic than the 17α-isomer and the 17β-isomer was also a stronger inhibitor of 17β-oestradiol-3H uptake in uterus and vagina than the 17α-isomer. This indicates a relationship between uptake in the target organs and oestrogenic activity. Progesterone and cortisol given before oestradiol-3H did not depress the uptake of radioactivity. Testosterone if anything stimulated the uptake. The uptake in liver and muscle was essentially not inhibited.

EFFECT OF ESTROGEN, PROGESTERONE AND TESTOSTERONE ON THE INCORPORATION OF L-VALINE-1-C14 INTO PROTEIN OF THE RAT LIVER AND UTERUS.

The influence of progesterone on the uptake of L-valine-1-C14 into the trichloroacetic acid precipitated protein of rat liver and rat uterus has been studied in normal and pregnant rats. Rats were treated 6 hr before experiments with combinations of estradiol, progesterone and in some instances testosterone. L-Valine-1-C14 was then injected into the tail vein, or liver and uterine slices were incubated with L-valine-1-C14. After trichloroacetic acid extraction and drying, aliquots were dissolved in hyamine hydroxide and counted in a scintillation counter. Hormonal administration was shown to affect the uterus uptake but not that of the liver. Theincreased uptake in the uterus after estrogen administration was depressed after the addition of progesterone. Testosterone had no effect. Liver and uterine slices from pregnant rats at 6 and 16 days of gestation were incubated with L-valine-1-C14. A significant increase (P < 0.01) was shown in the liver uptake of Lvaline-1-C14 between rats at 6 days and 16 days of gestation. The uteri similarly showed a significant (P < 0.005) increase in uptake. There is, therefore, an increasing influence of advancing pregnancy on the uptake of Lvaline-1-C14 in vitro into both liver and uterus. (Endocrinology74: 1, 1964)