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PubMed1984

Pharmacokinetics of capacity-limited tissue distribution of methicillin in rabbits.

Single-dose and steady-state studies were carried out in rabbits to characterize the pharmacokinetics of methicillin elimination and tissue distribution. Serum methicillin concentrations after single doses exhibited a biexponential decline with a mean terminal half-life of 27 +/- 5 min. Steady-state volume of distribution (Vdss) decreased twofold as doses increased from 5 to 125 mg/kg, while total clearance was consistent over this dosage range. During steady-state infusions of 8.7-87.2 mg/kg/h, the serum and extravascular fluid concentrations increased in proportion to dose, while clearance remained constant. Methicillin tissue concentrations did not increase in proportion to dose and serum concentration, and the Vdss measured from tissue recovery decreased as dosage and serum concentrations increased. Central compartment volume and serum protein binding did not change. The cause of the dose-dependent change in Vdss was a capacity-limited uptake of methicillin into essentially all nonexcretory tissues. This process was described by a partial physiological pharmacokinetic model based on the actual weights or volumes of the rabbit tissues. Distribution into extracellular fluids was assumed to be complete, while entry into cellular, nonexcretory tissue became capacity limited as the Km (17.2 micrograms/mL) was exceeded. The result was a decline in Vdss with increasing serum concentrations to a limiting value which approached the volume of the central space (Vc) and was similar to the extracellular water volume of the rabbit (0.17 L/kg). In the dosage range where total clearance was independent of serum concentration, the distribution of methicillin was concentration dependent and could be predicted by equations derived from the Michaelis-Menten equation.

Animals↗

PubMed2005

Tissue distribution and ontogeny of organic cation transporters in mice.

Organic cation transporters (Octs) play an important role in transporting cationic xeno- and endobiotics across biological membranes. Little is known about Octs in mice; therefore, the tissue distribution and developmental changes in the mRNA expression of Octs in mice were quantified. Oct1, Oct2, Oct3, Octn1, Octn2, and Octn3 mRNA expression was quantified in 14 tissues from male and female mice using the branched DNA signal amplification assay. Oct1 mRNA expression was highest in kidney, followed by liver. Oct2 mRNA was almost exclusively expressed in kidney, with male mice having twice that in female mice. The higher expression of Oct2 in male mice is due to testosterone. Oct3 mRNA was most highly expressed in placenta, ovary, and uterus, but was expressed at low levels in most tissues. Octn1 and Octn2 mRNA expression was similar, with the highest levels in kidney followed by small intestine. Octn3 mRNA was almost exclusively expressed in testes. The developmental expression of Oct1, Oct2, Octn1, and Octn2 mRNA in kidneys as well as Oct1 in liver was determined in young mice. Ontogenic expression data indicate that each of the Octs approached adult expression levels by about 3 weeks of age. The gender difference in Oct mRNA expression did not become apparent until day 30 after birth. The differences in tissue distribution of the Octs may play an important role in drug disposition to various tissues. Furthermore, low expression of the Octs in young animals may affect the pharmacokinetic behavior of drugs compared with that in adults.

Aging↗

PubMed2001

Pharmacokinetics and tissue distribution of piperine in animals after i.v. bolus administration.

A reverse phase HPLC method to determine piperine, a pungent constituent of black pepper, in rabbit serum and various tissues of the rat was developed. A pharmacokinetic study was performed in rabbits and tissue distribution studies were carried out in rats. High reproducibility was achieved in quantitative analysis over the concentration range of 0.2-20 micrograms/ml serum. After bolus intravenous administration of piperine at a dose of 10 mg/kg, the serum concentration--time curve fitted the two-compartment open model. The tissue distribution pattern of piperine in rats also supports the two-compartment open model.

Alkaloids↗

PubMed1985

Analysis of nonlinear tissue distribution of quinidine in rats by physiologically based pharmacokinetics.

The nonlinear tissue distribution of quinidine in rats was investigated by a physiologically based pharmacokinetic model. Serum protein binding of quinidine showed a nonlinearity over the in vivo plasma concentration range. The blood-to-plasma concentration ratio (Cb/Cp) of quinidine also showed a concentration dependence. The steady-state volume of distribution (Vss) determined over the plasma concentration range from 0.5 to 10 micrograms/ml was 6.0 +/- 0.45 L/kg. The tissue-to-plasma partition coefficient (Kp) of muscle, skin, liver, lung, and gastrointestinal tract (GI) showed a nonlinearity over the in vivo plasma concentration range of quinidine, suggesting saturable tissue binding. The concentration of quinidine in several tissues and plasma was predicted by a physiologically based pharmacokinetic model using in vitro plasma protein binding and the Cb/Cp of quinidine. The tissue binding parameters were estimated from in vivo Kp values. The predicted concentration curves of quinidine in each tissue and in plasma showed good agreement with the observed values.

Animals↗

PubMed1995

Modulation of the antitumor effect and tissue distribution of highly branched (1-->3)-beta-D-glucan, SSG, by carrageenan.

The action of carrageenan (CAR), a representative blocking reagent for phagocytes, on the antitumor effect and tissue distribution of highly branched (1-->3-beta-D-glucan, SSG, was examined. CAR inhibited the antitumor effect of intraperitoneally administered SSG only when applied before inoculation of the tumor, and had little effect when applied after tumor inoculation. A similar result was observed when SSG was administered intralesionally. In contrast, CAR had considerable effect on tissue distribution of i.p. SSG. The differences with respect to the results in normal mice were: 1) the distribution of SSG from the peritoneal cavity to the rest of the body was inhibited, 2) large numbers of peritoneal exudate cells (PEC) were produced and a relatively high concentration of 3H-SSG was found in the PEC fraction 48h after administration of 3H-SSG, 3) one week after administration, 3H-SSG was distributed to throughout the body but the amount of 3H-SSG distributed was lower than in normal mice, 4) a significant amount of 3H-SSG was recovered from ligaments (containing omental milky spots, peritoneum, mesentery and associated fat) in which negligible amounts were found in normal mice. The results suggest that the inhibition of the antitumor effect of SSG by CAR probably results from the prevention of the natural resistance of mice which is related to phagocytic function, and that the distribution of SSG to throughout the body is significantly modulated by CAR.

Animals↗

PubMed2005

[Cloning, expression and sequence analysis and tissue distribution of angiotensin-converting enzyme 2 (ACE2) gene in adult mice].

OBJECTIVE: o clone angiotensin-converting enzyme 2(ACE2) gene, to analyze its amino acids and nucleotides sequence and to investigate tissue distribution of ACE2 in adult mice. METHODS: The full-length ACE2 encoding sequence was amplified from the RNA of mice kidney tissue by RT-PCR technique, cloned into plasmid pGEM-T easy, then subcloned into plasmid pcDNA3.1+. After identification of DNA sequence, the recombinant plasmid pmACE2 was transfected into Cos7 cells with lipofectin reagent. The transient expression of ACE2 molecule was detected by SDS-PAGE. Sequence analysis was conducted with CLUSTALX program. Tissue distribution of ACE2 in mice was detected by RT-PCR. RESULTS: A fragment about 2.6 kb was amplified and the recombinant plasmid pmACE2 was confirmed by two-enzyme digesting and DNA sequencing. The cloned DNA sequence was consistent with that previously reported, except for 3 variations: A701G, T1102C and T1330C. SDS-PAGE proved that expression of a soluble, truncated products form of ACE2 was a glycoprotein of approximately 80 kD in Cos7 cells. The predicted mice ACE2 sequence contained an N-terminal signal sequence (amino acid residues 1-18), a single HHEMGHIQ zinc-binding domain (amino acid residues 373-380) and C-terminal membrane anchor (amino acid residues 738-765). Mice ACE2 showed 84 % identity with that of human, and 90 % identity with that of rat. Expression of ACE2 was the greatest in lungs, hearts and kidneys, and moderate levels were also detected in testes and livers. CONCLUSION: Mice ACE2 gene has been cloned and successfully expressed in vitro. The tissue-specific expression of ACE2 in different species is not identical.

Amino Acid Sequence↗

PubMed1980

Tissue distribution of antitumor drugs associated with polyalkylcyanoacrylate nanoparticles.

Polymethylcyanoacrylate nanoparticles, polyethylcyanoacrylate nanoparticles, and free 3H-dactinomycin and 3H-vinblastine were studied with emphasis on their distribution pattern in rat tissues after intravenous administration. The adsorption of cytostatic drugs to polyalkylcyanoacrylate nanoparticles can modify drug distribution in tissues. Particularly with vinblastine, modification of drug disposition is important. Data are given concerning the formation and stability of nanoparticle--drug complexes. Polyalkylcyanoacrylate nanoparticles seem to be an interesting drug carrier owing to their size, structure, degradability, and drug sorptive properties.

Adsorption↗

PubMed2003

Fetal and maternal tissue distribution of the new fluoroquinolone DW-116 in pregnant rats.

We investigated maternal and fetal tissue distribution of DW-116, a newly developed fluoroquinolone with a broad antibacterial spectrum against both G(+) and G(-) bacteria, in pregnant rats. After oral administration of [14C]-DW-116 (labeled 1 mg and unlabeled 500 mg/kg) to female rats on the 18th day of gestational, groups of three rats were killed at various time points up to 24 h, and plasma and tissues were collected, processed and analyzed. [14C]-DW-116 was rapidly absorbed, and distributed into the maternal and fetal tissues, and it declined in a biphasic manner with elimination half-lives (t(1/2)) of 10-15 h and mean residence times (MRT(0-24 h)) of 4-9 h. The radioactivity in most tissues of both dams and fetus reached its peak within 1 h and radioactivity levels of up to 10-25% of the peak level were maintained until 24 h after dosing. Among various tissues, the radioactivity in the maternal lungs was the highest (27 times that of plasma) at the C(max). Radioactivity in other tissues including liver, kidney, heart, lung, brain, spleen, mammary gland, placenta, ovary and uterus was higher than that in the maternal plasma (one- to three-fold). The tissue-to-plasma partition coefficient (K(p), AUC(0-24 h,tissue)/AUC(0-24 h,plasma)) of [14C]-DW-116 in maternal tissues was highest in the lung (K(p)=3.7), followed by the spleen (2.2), kidney (2.0), liver (1.8), heart (1.5), placenta (1.3), brain (1.3), ovary (1.1), uterus (1.1), and mammary gland (1.0). The tissue-to-plasma partition coefficient values in fetal tissues were heart (K(p)=2.2), kidney (2.1), liver (1.9), lung (1.6) and brain (1.4). When lactating rats were given a single oral dose of [14C]-DW-116, the radioactivity was rapidly secreted into the milk with K(p) of 1.7 at T(max) (0.5 h). These results indicate that DW-116 or its related metabolite(s) rapidly cross the blood-placenta and blood-milk barrier, extensively distribute into the fetal tissues, and are eliminated from the body in a prolonged manner. This study sheds insights into the maternal and fetal tissue distribution of DW-116 and will be useful for assessing both therapeutic and toxicological relevance of DW-116 in pregnant subjects.

Administration, Oral↗

PubMed2003

Tissue distribution of a new photosensitizer ATX-S10Na(II) and effect of a diode laser (670 nm) in photodynamic therapy.

The aims of the present study were to analyse the quantitative tissue distribution of ATX-S10Na(II) and to investigate the maximal effect of a diode laser and the irradiation conditions required to obtain this effect in photodynamic therapy (PDT) with ATX-S10Na(II). Spectrofluorometry was used to obtain quantitative tissue distribution of ATX-S10Na(II) in Colon 26 carcinoma-bearing mice as a function of time following administration. Next, transplanted tumours of mice with or without ATX-S10Na(II) were treated with the diode laser under conditions in which power density and irradiation time were varied. Tumour tissue concentrations of ATX-S10Na(II) were higher than in all tissues at all intervals following administration. The uptake of ATX-S10Na(II) by most tissues was rapid, with maximal concentrations occurring 1 h after i.v. injection, and ATX-S10Na(II) was almost excreted within 24 h after administration. The maximal depth of necrosis induced by PDT in the treated tumour was 7.9 mm under conditions in which power density was 160 mW/cm2 and total dose was above 100 J/cm2. PDT with ATX-S10Na(II) and the diode laser is useful for the treatment of superficial cancers.

Animals↗

PubMed1996

Determination of tissue distribution of an intramuscular plasmid vaccine using PCR and in situ DNA hybridization.

The increasing use of nucleic acid-based therapeutics has created a need for new methods of determining tissue distribution and levels. Radiolabel methods may not always be appropriate because nucleic acids are easily degraded. Quantitation using the polymerase chain reaction (PCR) has the advantage that only continuous stretches of DNA will be amplified. In situ hybridization allows detection of specific sequences in histological preparations. We have used quantitative PCR and in situ hybridization techniques to study the pharmacokinetics and distribution of PGagPol (a potential anti-HIV plasmid vaccine) in rabbits. Samples were obtained 4 hr, 24 hr, 7 days, and 28 days after intramuscular injection of 100 micrograms or 400 micrograms of plasmid. A simplified procedure for collecting and processing tissues for PCR that minimizes the risk of contamination was developed. Using PCR, plasmid was found principally in the skin and muscle of the injection site and in blood plasma. At 4 hr after dosing with 400 micrograms, the plasmid was detected at the injection site with mean copy numbers of 10(6) (in muscle) and 4 x 10(4) (in skin) per microgram of tissue. Plasmid copy number declined rapidly in muscle during the first 24 hr and was undetectable at 7 and 28 days after injection. The decline was slower in the skin, and the plasmid was still detectable at 28 days. With in situ hybridization, plasmid was detected in muscle, mainly in the perimysium and to a lesser degree in the endomysium and within the muscle fibers. These data indicate that quantitative PCR and in situ hybridization are sensitive methods for examining tissue distribution of DNA used for gene therapy.

Animals↗

PubMed1998

Pharmacokinetics and tissue distribution of a new carbapenem DA-1131, after intravenous administration to mice, rats, rabbits and dogs.

The pharmacokinetic parameters including tissue distribution and/or biliary excretion of DA-1131, a new carbapenem, were evaluated after intravenous (iv) administration to mice, rats, rabbits, and dogs. After i.v. administration to mice (20, 50, 100, and 200 mg kg-1), rats (50, 100, 200, and 500 mg kg-1), rabbits (20, 50, 100, and 200 mg kg-1), and dogs (10, 20, 50, 100, and 200 mg kg-1), the pharmacokinetic parameters of DA-1131 seemed to be independent of DA-1131 doses studied in all four animal species. However, the renal clearance of percentage of i.v. dose of DA-1131 excreted in 24 h urine as unchanged drug decreased significantly in rabbits (from 200 mg kg-1) and dogs (from 100 mg kg-1) due to reduced kidney function induced by DA-1131. The creatinine clearance decreased significantly in rabbits at 200 mg kg-1 compared with that in the control rabbits (0.466 versus 4.31 mL min-1 kg-1). Renal active secretion of DA-1131 was observed in rabbits and was less considerable in rats, but renal active reabsorption of DA-1131 was observed in dogs. Although DA-1131 was widely distributed in all tissues studied in mice (20-200 mg kg-1), rats (200 mg kg-1), rabbits (50 mg kg-1), and dogs (50 mg kg-1) affinity of DA-1131 for tissues was low: the tissue-to-plasma concentration ratios were greater than unity only in the kidney and/or liver. The low affinity of DA-1131 for tissues was also supported by relatively low values of the apparent volume of distribution at steady state in rats (147-187 mL kg-1), rabbits (91.7-148 mL kg-1), and dogs 243-298 mL kg-1). The contribution of biliary excretion of unchanged DA-1131 to nonrenal clearance of DA-1131 seemed to be minor in rats (200 mg kg-1) and dogs (50 mg kg-1); the percentages of i.v. dose excreted in 8 h bile as unchanged DA-1131 were 1.76 and 2.71% after i.v. administration of the drug to rats and dogs, respectively.

Animals↗

PubMed2004

Plasma pharmacokinetics and tissue distribution of the breast cancer resistance protein (BCRP/ABCG2) inhibitor fumitremorgin C in SCID mice bearing T8 tumors.

Multidrug resistance (MDR) remains a major obstacle in the treatment of human cancers. The recently discovered breast cancer resistance protein (BCRP/ABCG2) has been found to be an important mediator of chemotherapeutic MDR. Fumitremorgin C (FTC) is a selective and potent inhibitor of BCRP that completely inhibits and reverses BCRP-mediated resistance at micromolar concentrations. We report a study of the pharmacokinetics and tissue distribution of FTC when administered intravenously (IV) at a dose of 25 mg/kg to female SCID mice bearing the BCRP-overexpressing human ovarian xenograft Igrov1/T8 tumors. Plasma pharmacokinetics and tissue distribution of FTC in various organs and tissues were studied. In addition, the effect of FTC administration on the expression of BCRP in T8 tumors was also assessed by RT-PCR. Administration of a single FTC IV dose did not appear to cause any major toxicities. The resulting pharmacokinetic data were fit to a two-compartment model using NONMEM and the FTC clearance was determined to be 0.55 ml/min (25.0 ml/min/kg) with a 56% inter-animal variability. Area under the plasma concentration time curve was determined by Bailer's method and was calculated to be 1128+/-111 microg min/ml. FTC was widely distributed in all tissues assayed with highest concentrations found in lungs, liver and kidney in decreasing order, respectively. FTC did not appear to have any effect on the expression of BCRP in T8 tumors. Less than 2% of the administered dose was recovered in the urine and feces after 24 h, suggesting hepatic metabolism as a primary mechanism of elimination. The current study can be used as a basis for future animal or in vivo studies with FTC designed to further understand the impact of BCRP on drug resistance.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed1998

Human mitochondrial transmembrane metabolite carriers: tissue distribution and its implication for mitochondrial disorders.

Mitochondrial transmembrane carrier deficiencies are a recently discovered group of disorders, belonging to the so-called mitochondriocytopathies. We examined the human tissue distribution of carriers which are involved in the process of oxidative phosphorylation (adenine nucleotide translocator, phosphate carrier, and voltage-dependent anion channel) and some mitochondrial substrate carriers (2-oxoglutarate carrier, carnitine-acylcarnitine carrier, and citrate carrier). The tissue distribution on mRNA level of mitochondrial transport proteins appears to be roughly in correlation with the dependence of these tissues on mitochondrial energy production capacity. In general the main mRNA expression of carriers involved in mitochondrial energy metabolism occurs in skeletal muscle and heart. Expression in liver and pancreas differs between carriers. Expression in brain, placenta, lung, and kidney is lower than in the other tissues. Western and Northern blotting experiments show a comparable HVDAC1 protein and mRNA distribution for the tested tissues. Patient's studies showed that cultured skin fibroblasts may not be a reliable alternative for skeletal muscle in screening for human mitochondrial carrier defects.

Adenine Nucleotides↗

PubMed1990

Rat brain natriuretic peptide--tissue distribution and molecular form.

Using an antiserum against the ring structure of rat brain natriuretic peptide (rat BNP), we have established a specific radioimmunoassay (RIA) for rat BNP and elucidated its tissue distribution and molecular form. Rat BNP-like immunoreactivity (-LI) was detected in the highest amount in cardiac extracts (574.0 +/- 138.8 pmol/g in the atrium and 4.3 +/- 1.1 pmol/g in the ventricle). The secretory rate of rat BNP-LI from the perfused whole heart was 50.0 +/- 1.9 fmol/min, about 60% of which was maintained even after atrial removal. We also detected rat BNP-LI throughout the spinal cord (134-175 fmol/g), although no detectable amount was present (less than 100 fmol/g) in other tissues including the brain. High performance-gel permeation chromatography and reverse phase-high performance liquid chromatography coupled with the RIA revealed that rat BNP with 45 amino acids is a major storage form as well as a secretory form of rat BNP-LI in the heart. The major component in the spinal cord was also rat BNP. These findings indicate that the tissue distribution and the processing pattern of rat BNP are different from those of atrial natriuretic peptide and porcine BNP, thereby suggesting the presence of complicated diversity of the natriuretic peptide system.

Animals↗

PubMed1990

Tissue distribution of a coliphage and Escherichia coli in mussels after contamination and depuration.

Experiments were undertaken to determine the tissue distribution of Escherichia coli and a coliphage after contamination of the common mussel (Mytilus edulis). Mussels were contaminated with high levels of feces-associated E. coli and a 22-nm icosahedral coliphage over a 2-day period in a flowing-seawater facility. After contamination, individual tissues were carefully dissected and assayed for E. coli and the coliphage. Contaminated mussels were also analyzed to determine the tissue distribution of the contaminants after 24- and 48-h depuration periods. The majority of each contaminant was located in the digestive tract (94 and 89% of E. coli and coliphage, respectively). Decreasing concentrations were found in the gills and labial palps, foot and muscles, mantle lobes, and hemolymph. Our results indicate that contamination above levels in water occurred only in the digestive tract. Contaminated mussels were depurated in a commercial-scale recirculating UV depuration system over a 48-h period. The percent reductions of E. coli occurred in the following order: digestive tract, hemolymph, foot and muscles, mantle lobes, and gills and labial palps. The percent reductions of the coliphage were different, occurring in the following order: hemolymph, foot and muscles, gills and labial palps, mantle lobes, and digestive tract. Our results clearly demonstrate that E. coli and the coliphage are differentially eliminated from the digestive tract. The two microorganisms are eliminated at similar rates from the remaining tissues. Our results also clearly show that the most significant coliphage retention after depuration for 48 h is in the digestive tract. Thus, conventional depuration practices are inappropriate for efficient virus elimination from mussels.

Animals↗

PubMed2004

Tissue distribution of bitespiramycin and spiramycin in rats.

AIM: To investigate the tissue distribution of bitespiramycin (BSPM) and spiramycin (SPM) in rats. METHODS: Liquid chromatographic-mass spectrometric assay was applied for the determination of three major components (isovalerylspiramycins, ISV-SPMs) of BSPM and their major active metabolites (SPMs) in rat tissues and plasma after an oral dose of bitespiramycin, as well as SPMs. RESULTS: High levels of drug concentrations were observed in most tissues, especially in the liver, stomach, intestine, spleen, lung, womb, and pancreas. BSPM persisted long time in many rat tissues such that the drug concentration in spleen was 69.4 nmol/g at 60 h post-dose and it was still above the minimum inhibitory concentration of many susceptible pathogens. At 2.5 h post-dose, the total concentrations of ISV-SPMs and SPMs achieved in tissues were from 6 to 215 times higher than the corresponding concentrations in plasma. At 2.5 h post-dose, the mean C(t)/C(p) of BSPM appeared to be 2- or 3-fold those of SPM in most tissues. The tissue to plasma concentration ratios following oral dose of BSPM were higher than those of SPM in most tissues. The drug was not detected in brain and testis after a single dose of BSPM and SPM. CONCLUSION: Both BSPM and SPM penetrate into rat tissues well and BSPM has higher tissue affinity than SPM.

Administration, Oral↗

PubMed1997

Tissue distribution and localization of natriuretic peptide receptor subtypes in stroke-prone spontaneously hypertensive rats.

OBJECTIVE: To investigate tissue distribution and localization of the natriuretic peptide receptor (NPR) subtypes' messenger RNA (mRNA) and to compare their expression between stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto (WKY) rats. METHODS: Total RNA was extracted from organs of SHR-SP and WKY rats aged 13 weeks. The mRNA level was examined by RNase protection assay. The localization of the transcripts was determined by in-situ hybridization. RESULTS: In SHR-SP aged 13 weeks, NPR-A was expressed most abundantly in the adrenal gland, lung and aorta, in that order. NPR-B was expressed highly in the uterus and ovary, and also in the lung, adrenal, and brain. NPR-C was expressed predominantly in the atrium and mesentery, less so in the lung, vein, and kidney. In the adrenal gland, NPR-A was expressed mainly in zona glomerulosa cells. In the atrium, NPR-C was expressed throughout the wall. In the mesentery, NPR-C mRNA was detected mainly in adipocytes. In the kidney, NPR-C was found predominantly in podocytes. Whereas the levels of expression of NPR subtypes in most tissues examined did not differ between SHR-SP and WKY rats, the NPR-C mRNA level was significantly greater in the kidneys of SHR-SP than it was in those of WKY rats. CONCLUSIONS: These results indicated that each NPR subtype had a distinct tissue distribution pattern and that the expression of NPR-C in the kidneys of SHR-SP was greater than that in the kidneys of WKY rats.

Animals↗

PubMed1991

20-[18F]fluoromibolerone, a positron-emitting radiotracer for androgen receptors: synthesis and tissue distribution studies.

To develop an androgen receptor-based, positron-emitting imaging agent for prostate tumors, we have prepared 20-fluoromibolerone (F-Mib) and evaluated its tissue distribution. This compound was synthesized in eight steps from 7 alpha-methyl-19-nortestosterone, with fluorine introduced in the penultimate step by fluoride ion displacement on a spirocyclic sulfate. Fluoromibolerone was obtained in 9%-19% radiochemical yield (decay corrected), at 1.5 hr after bombardment, with an effective specific activity of 217-283 Ci/mmol. The relative binding affinity of F-Mib is 53 (versus R1881 = 100 or mibolerone = 118). In tissue distribution studies in diethylstilbestrol-treated male rats, 18F-Mib demonstrates high target/tissue uptake efficiency and selectivity: the prostate uptake at 0.5 hr and 4 hr is 1.0%-1.3% injected dose/gram tissue (ID/g) and 0.5%-0.6% ID/g, respectively; the prostate-to-blood and the prostate-to-muscle (non-target) ratios are both ca. 4 at 0.5 hr, and increase to ca. 12 by 4 hr after injection. The observed distribution of 18F-Mib suggests that it may be useful for in vivo imaging of prostatic tumors in man by positron emission tomography.

Animals↗