US3716631A - Use of radioactive compounds to determine fat absorption - Google Patents

Use of radioactive compounds to determine fat absorption Download PDF

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Publication number
US3716631A
US3716631A US00801771A US3716631DA US3716631A US 3716631 A US3716631 A US 3716631A US 00801771 A US00801771 A US 00801771A US 3716631D A US3716631D A US 3716631DA US 3716631 A US3716631 A US 3716631A
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radioactive
compound
formula
group
urine
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US00801771A
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J Steggerda
A Houtman
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MAALLINCKRODT DIAGNOSTICA (HOLLAND) BV WESTERDUINWEG 3 1755 LE PETTEN NETHERLANDS
US Philips Corp
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US Philips Corp
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Assigned to MAALLINCKRODT DIAGNOSTICA (HOLLAND) B.V., WESTERDUINWEG 3, 1755 LE PETTEN, THE NETHERLANDS reassignment MAALLINCKRODT DIAGNOSTICA (HOLLAND) B.V., WESTERDUINWEG 3, 1755 LE PETTEN, THE NETHERLANDS CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE DATE: SEPTEMBER 3, 1984 Assignors: BYK-MALLINCKRODT CIL B.V.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/13—Tracers or tags

Definitions

  • the invention relates to the absorption of fats through the intestinal wall and has for its object to find disturbances in the fat absorption and to establish the extent of the disturbance.
  • a frequently used method is that in which disturbances in the fat absorption are determined by faces examination.
  • a known quantity of fat is administered to a patient for a period of a few days, usually 5 days, the faces excreted during the last few days of the above-mentioned period are collected, and the quantity of fat present in the feces is then determined quantitatively.
  • the difference between the administered and excreted quantity of fat is assumed to be absorbed in the body.
  • the first few days on which the fat diet is administered is considered as a starting period in which no feces examination takes place.
  • it is a first requisite for the success of the examination that the quantity of fat determined in the feces originates exclusively from a known quantity of administered fat.
  • inert indicators are used which are administered together with -the fat and limit the quantity of feces to be examined.
  • the therapy can be started comparatively late.
  • an accurately determined quantity of radioactive labelled iodine glyceroltrioleate is administered to the patient.
  • the patient is bled and the radioactivity of the blood samples is determined.
  • This method has the drawback that the examination is unpleasant to the patient and the accuracy to be desired in many cases because the method is based on comparative examination and the patient must satisfy certain standard conditions. Moreover precautions must be taken that no supply of radioactive iodine takes place in the body, notably in the thyroid gland. It is therefor desirable that during the examination according to this method the thyroid gland is blocked.
  • the method according to the invention is based on the recognition of the fact that disturbances in the fat absorption can be determined by means of a urine examination. It has been found more particularly that disturbances in fat equilibrium can be determined by using compounds which, as regards the intestinal absorption, behave as fatty acids or esters of fatty acids, for example, glycerol esters of fatty acids, and after absorption in the body are degradated therein, at least one degradation product coming in the urine.
  • the compounds according to the invention are labelled radioactive and that in such manner that upon degradation of the compound in the body at least the degradation product which has come in the urine is radioactive.
  • the method according to the invention has the following advantages:
  • the absorption through the intestinal wall is measured and not, as is the case with the method on feces examination, the sum of the non-absorbed fat, the fat excreted through the intestinal wall out of the body, and the bacterial fat.
  • the urine examination is very simple. It is sufficient to determine the volume of the received urine and the radioactivity in a part thereof.
  • Radioactive compounds according to the invention which are suitable for use in determining disturbances of the fat equilibrium may be represented by the general formula I in which formula X hydroxy group, an alkoxy group containing one to three carbon atoms or a branched or non-branched alkyl group having one to four carbon atoms,
  • Hal a halogen atom chosen from the group consisting of a chlorine, bromine and iodine atom,
  • R carboxyl group, COOMe group, in which Me is a metal atom and preferably an alkali metal atom, or a COOR' group, wherein R is an aliphatic hydrocarbon radical which may be substituted with one to two hydroxy groups, I
  • the symbol H means that the phenyl nucleus with tritium is labelled radioactive (generally labelled), the symbol C that the phenyl nucleus contains radioactive C atoms, the symbol I denotes a iodine isotope 1 or I) and X means a hydrogen atom or an alkali metal atom.
  • the radioactive compounds according to the invention are new and may be prepared in a manner known for similar compounds or in a manner analogous thereto.
  • the compounds according to the invention may be prepared by: 1
  • R is a lower alkyl group and r.a. denotes that the part of the compound enclosed by the broken line is radioactive
  • E Xm OR is obtained, in which formula X, Hal, R, r.a., m, n and p have the above meanings;
  • formula X is an alkoxy group having one to three carbon atoms or a branched or non-branched alkyl group having one to four carbon atoms
  • Hal is a halogen atom selected from the group consisting of a chlorine, bromine and iodine atom
  • r.a. denotes that the part of the compound enclosed by the broken line is radioactive
  • the phenol is reacted in an alkaline solution with the said reagent, initially at room temperature and then on steam bath.
  • Alkylation may also be carried out by reaction with an alkyl halide in the presence of a base or after the starting product has been converted into the acid chloride, for example, by reaction with thionyl chloride, PCl or PCI S converting this acid chloride with an alcoholate, for example, sodium ethanolate.
  • re c and h For the saponification of esters the conventional methods may be used, for example, heating with an alcoholic NaOH solution succeeded by acidification and pouring in water.
  • the m-phenyl fatty acids may be esterified by reacting the acids for a longer period of time with alcohols and preferably with absolute ethanol at a temperature which may vary between room temperature and the boiling point of the reagent.
  • the reaction may be catalyzed by a small quantity of a mineral acid.
  • the esters may also be prepared by first converting the acids with thionyl chloride or a similar acid chlorination agent to the corresponding acid chlorides which are then converted in alkaline medium with an alcohol.
  • an inert solvent for example, benzene or chloroform.
  • halogenation of the aromatic ring use is preferably made of radioactive N-bromosuccinimide, N-chlorosuccinimide or a solution of KJ-J, in an NaOH-boric acid buffer (J. Org. Chem. 30, 304 (1965 re f and g).
  • the reduction of a double bond may be carried out, for example, with zinc amalgam or mercury amalgam according to the method by Clemmensen or catalytically, for example, under the influence of a platinum catalyst or a palladium on carbon catalyst.
  • the starting products in the preparation of the compounds according to the invention may also be prepared according to known methods or according to methods analogous thereto.
  • these starting substances may be obtained by reacting a compound of the formula in which formula X is a hydroxy group, an alkoxy group having one to three carbon atoms or an alkyl group having one to four carbon atoms and m or 1, with a compound of the formula in which p 2 -20 (inclusive) in the presence of a Friedel Crafts catalyst and at a temperature of 0 5 C, in which a compound of the formula X O H:
  • the resulting radioactive acid may serve as a starting product for the methods mentioned sub b and d according to which the phenol group is alkylated (method b) and the radioactive acid is converted into the ester or the salt thereof (method d), respectively.
  • radioactive ester is halogenated directly with radioactive halogen or a halogen compound, the resulting radioactive ester be converted subsequently, if desired, by hydrolysis into the corresponding acid (method 0).
  • Another mode of preparing the starting products consists in acylating radioactive benzene or a radioactive benzene derivative of the formula 1 OCH:
  • the radioactive compounds thus prepared may then be converted into the compounds according to the invention by using the reduction mentioned sub a.
  • the above radioactive benzene or benzene derivative mentioned as a starting substance contains one or several radioactive atoms, for example, a tritium atom, a C atom or a atom.
  • the position of the radioactive atom in the benzene (derivative) molecule is of no essential importance.
  • the radioactive atom may form part of the benzene ring or be in the substituent of the benzene ring denoted by X.
  • the halogen substituent of the benzene ring is radioactive. If the benzene derivative contains two halogen atoms, both atoms or one of both atoms may be radioactive.
  • the starting products of the method mentioned sub f may be obtained by reacting a compound of the formula in which formula X, Hal, r.a., m, n and p have the meanings mentioned with the method f, with the methyl ester or ethyl ester of bromoacetic acid, a compound of the formula being obtained, in which formula X, Hal, r.a., m, n and p have the above meanings and R is a methyl group or an ethyl group and then dehydrating the resulting product.
  • the starting substances of method g are prepared in the same manner as described above, but with this difference that instead of the methyl ester or ethyl ester of bromoacitic acid, the methyl ester or ethyl ester of bromocrotonic acid is used.
  • the above-mentioned aldehyde starting product may be prepared by hydrogenating the corresponding acid chloride catalytically (Rosemund reduction) or reducing the corresponding ester according to the method by Bouveault-Blanc.
  • the starting products of the method mentioned sub h may be prepared by reducing a compound of the formula 0R u 1 l. 1
  • the starting substances used in method i are obtained by reacting a compound of the formula A CH Br, in which A is the group in which group X, Hal, r.a., m, n, p and q have the meanings indicated with method i, with Mg to form a compound of the formula ACh Mg-Br and reacting the resulting product in the presence of CdCl with a compound of the formula O OH in which formula q has the above meaning.
  • the starting substances of method k can be prepared by reacting a compound of the formula in which A is the group in which group X, Hal, r.a., m, n and p have the meanings denoted with method k, with a compound of the formula is obtained.
  • This latter compound is hydrolyzed with acid to form a compound of the formula I and then saponified with alkali, the starting product of the method mentioned sub k being obtained.
  • the cyclohexane morpholine reagent may be prepared according to known methods (Berichte 90,
  • a compound according to the invention contains a tritium atom a C atom, the compound produces a B radiation, whereas upon application of, for example, a .1 atom, the compounds according to the invention show a radiation.
  • both compounds having B radiation and 7 radiation may be used in the method according to the invention for determining disturbances of the fat absorption.
  • the compounds according to the invention can be processed in the conventional manner to pharmaceutical compositions suitable for oral administration, for example, tablets, coated tablets, capsules, water-soluble powders and oil dispersions.
  • the active substance is mixed with or dissolve or dispersed in a liquid or solid carrier, if desired while adding surface-active substances, for example, emulsifiers, furthermore lubricants, binding agents, flavoring substances and similar substances.
  • the prescriptions below may be used.
  • the expression active substance means tritiated phenyloctyl-carboxylic acid or the sodium salt thereof.
  • Prescriptions 1 Tablet five grns of active substance are mixed with 100 grns of lactose, 50 gms of sucrose and gms of a binding agent.
  • the mixture is granulated with water and 5 percent potato-starch, 2 percent talcum and 1 percent magnesium stearate are added to the granulate.
  • the resulting product is tabletted in the conventional manner.
  • Capsule five mgms of active substance are mixed with so much microcrystalline lactose (approximately 95 mgms) that a hardened gelatin capsule can be filled with the mixture.
  • Capsule five mgms of active substance are diluted with arachis oil and incorporated in a gelatin capsule.
  • Aqueous solution An aqueous solution is obtained by taking up 5 percent by weight of active substance in water to which approximately 0.1 percent of a preservative, for example, esters of p-hydroxybenzoic acid, has been added.
  • a preservative for example, esters of p-hydroxybenzoic acid
  • the success of the method of examination according to the invention depends upon the accuracy with which the quantity of radioactive compound which has come in the urine and hence the quantity of radioactivity occurring in the urine can be determined.
  • the accuracy greatly depends upon the recording power of the analysis apparatus used with regard to the used radioactivity ([3 or 7 radiation). For good results a minimum quantity of radioactivity occurring in the urine is necessary.
  • the dosing of the composition according to the invention is therefore preferably expressed in a quantity of radioactivity to be administered.
  • the preparation of the composition according to the invention it is desirable to convert the above-men tioned quantity of radioactivity to be administered into a quantity of the radioactive-compound to be administered, or to be processed in pharmaceutical compositions. Since the quantity of radioactivity which is produced by a compound according to the invention depends upon the number of radioactive atoms which the compound contains and the value of the radioactivity of the isotope used (half lifetime), the quantity of active compound to be administered or to be processed, will vary for each individual compound in accordance with specific radioactivity of the compound. In general a dose of from 0.1 to 50 mgms of active compound will give the desired results.
  • the active compounds present in the composition are taken up quantitatively in the body or for a certain percentage through the small intestine under the influence of secretion products of the liver (emulsifying activity) and the enzyme lipase originating from the pancreas (saponification). It has furthermore been found that the compounds according to the invention are degradated in the body according to the theory by Knoop to benzoic acid derivatives if an even number of CH-,. groups is present between the phenyl group and the carboxylic acid group or to phenyl-acetic acid derivatives if the number of -CH groups is odd.
  • Knoop involves that upon degradation of fatty acids in the body each time two carbon atoms are split off.
  • Knoop used fatty acids with an w-phenyl group namely phenylcapronic acid and phenylvaleric acid.
  • the final products of the degradation (benzoic acid and phenyl acid) are coupled in the liver with glycine to phenylacetal glycine and hippuric acid and then secreted in the urine.
  • the compounds according to the invention after degradation in the body to the above-mentioned benzoic acid derivatives and phenyl acetic acid derivatives are likewise detoxicated in the liver by coupling with glycine and are then secreted in the urine. It has been found, for example, that a quantity of S-tritiated phenyl-octyl-carboxylic acid-l administered to healthy people comes in the urine for substantially percent as radioactive hippuric acid.
  • the percentage of active compound which upon administration of a composition according to the invention is taken up in the body through the small intestine is determined by measuring the quantity of radioactivity of the collected urine fractions and expressing it in per cent of the total quantity of administered radioactivity.
  • Fecal fats were extracted from feces homogenates (approximately 3 gms) after acidification of the homogenates with concentrated HCl (0.1 ml per gram of homogenate) by adding 5 times the volume of methanol. After centrifuging the residue was washed two times with the same volume of methanol. The combined methanol extracts were evaporated to approximately 8 mls under reduced pressure. Then mils of water were added after which this solution was shaken three times with 20 mls of toluene. The toluene-extracted dyes were removed by passing the combined toluene extracts through a column of silicagel and then recovering them quantitatively by washing the column with toluene. The purified toluene extract was evaporated under reduced pressure and a part of the residue was counted in toluene-POPOP-PPO scintilation liquid.
  • the orally administered quantity of radioactivity is rapidly excreted for substantially 100 percent in the urine by healthy persons.
  • the excreted quantity of radioactivity in the urine after oral administration of the same dose is lower than in healthy persons.
  • the difference between the administered quantity of radioactivity and the quantity of radioactivity in the urine, expressed in percent of the administered quantity of radioactivity corresponds to the percentage of fat not absorbed by the body.
  • a radioactivity determination in the feces demonstrated in addition that no radioactive degradation product is stored in the body since the sum of the quantities of radioactivity found in the feces and in the urine is equal to the administered quantity.
  • hippuric acid as sodium salt were dissolved in a quantity of urine which contained 9.9 X 10 dpm l-I activity. If all the H activity originates from hippuric acid, the specific activity must be 4.40 X 10 dpm/g of hippuric acid.
  • the percipitate which was obtained after dissolving 30 gms of NaCl per 100 mls of urine the specific activity was determined as well as of the crystals which were obtained after crystallization of the precipitate from ethanol and of the crystals which were obtained after crystallization from water of the crystals obtained from ethanol. From the results it appeared that substantially all the radioactivity present in the urine was coupled to hippuric acid.
  • the tetrachloroethane layer is separated and the water layer is extracted with benzene.
  • the combined organic extracts are washed with water, dried on Na SQ, and evaporated.
  • the resulting ester is saponified by dissolving it in 30 mls of ethanol and ad ding to it a solution of 3.3 gms of NaOH in 19 mls of water. After heating on a steam bath for 30 minutes the solution is cooled, the sodium salt of 7 H-benzoylheptane carboxylic acid crystallizing out. After sucking off and washing with percent ethanol the resulting sodium salt is dissolved in 50 mls of water.
  • reaction mixture was extracted times with totally 300 mls of ether and the combined ether extracts were washed with water until the color was bright.
  • the ether was then evaporated in vacuo and the residue poured out in 300 mls of water, benzoylbutyric acid precipating. Yield 1.5 gms (43.4 percent), melting point 124-127 C.
  • a method of determining the degree of fat or fatty acid absorption in a mammal comprising orally administering to said mammal a measured amount of a radio-active compound of the formula wherein X is a moiety selected from the group consisting of hydroxy, alkoxy of l-3 carbon atoms and alkyl of 14 carbon atoms, Hal is a halogen selected from the group consisting of chlorine, bromine and iodine, R is a moiety selected from the group consisting of carboxyl, COO Me wherein Me is a pharmaceutically acceptable metal and COOR' wherein R' is aliphatic hydrocarbon of up to two carbon atoms unsubstituted or substituted with up to two hydroxy groups, m 0 or 1, n 0, l or 2, p 2-20 inclusive and wherein the broken line denoted by r.a.
  • the part of the compound enclosed by the broken line is radioactively labeled the degree of absorption of said radioactive compound having a previously determined and constant relationship to the degree of absorption of a fat or fatty acid, said radioactive compound when absorbed through the intestinal wall metabolizing to form at least one radioactive metabolite eliminated in the urine of said mammal, the total amount of said radioactive metabolite in said urine bearing a constant relationship to the total amount of the specific radioactive compound administered and determining by radioactive measurement the total amount of said radioactive metabolite in the urine.
  • the radioactive compound is of the formula 21 22 wherein r.a. donates that the phenyl nucleus contains at (CH COOR least one radioactive atom, R is a moiety selected from 2 a the group consisting of hydrogen, alkali metal, alkyl of 3H 7 D V 1 to 2 rb n ato d l l d p -4 12 wherein 3' denotes that the phenyl nucleus is labelled 5.
  • the radioactive with tritium and R is a moiety Selected from the group compound i f h fo l consisting of hydrogen and alkali metal.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
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  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US00801771A 1968-02-23 1969-02-24 Use of radioactive compounds to determine fat absorption Expired - Lifetime US3716631A (en)

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JP (1) JPS518937B1 (enrdf_load_stackoverflow)
BE (1) BE728805A (enrdf_load_stackoverflow)
DE (1) DE1908804A1 (enrdf_load_stackoverflow)
ES (1) ES363958A1 (enrdf_load_stackoverflow)
FR (1) FR8405M (enrdf_load_stackoverflow)
GB (1) GB1263756A (enrdf_load_stackoverflow)
NL (1) NL6802651A (enrdf_load_stackoverflow)
SE (1) SE348290B (enrdf_load_stackoverflow)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3907846A (en) * 1973-04-12 1975-09-23 Lilly Industries Ltd Preparation of substituted decenoic acids
US4065552A (en) * 1975-05-05 1977-12-27 Giovanni Giacomo Costa Method of detecting malignant neoplasms
DE2947500A1 (de) * 1979-11-24 1981-05-27 Hoechst Ag, 6000 Frankfurt Radiojodierte (omega) -phenylfettsaeuren, ihre herstellung und praeparate zur szintigraphischen untersuchung desherzmuskels und der leber
US4970146A (en) * 1986-01-16 1990-11-13 Havbrukskjemi A/S Method of determining absorbed nutriment in living organisms
US5347030A (en) * 1987-10-23 1994-09-13 The Board Of Regents Of The University Of Michigan Radioiodinated phospholipid ether analogues and methods of using same
WO1997019705A1 (en) * 1995-12-01 1997-06-05 Elmaleh David R Stereoisomers of fatty acid analogs for diagnostic imaging
US20060258009A1 (en) * 2003-08-06 2006-11-16 Jandacek Ronald J Use of non-absorbable fat in determining dietary fat absorption

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5497273A (en) * 1978-01-10 1979-08-01 Nippon Carbide Ind Co Ltd Method of controlling vermin of useful plants and agricultural covering material to be used therefor
JPS54184388U (enrdf_load_stackoverflow) * 1978-06-19 1979-12-27

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3061510A (en) * 1958-08-01 1962-10-30 Olin Mathieson Radioactive iodinated (i131) fatty material admixed with wax-like material in capsule
US3466361A (en) * 1968-04-18 1969-09-09 Atomic Energy Commission Technetium-99m labeled chelates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3061510A (en) * 1958-08-01 1962-10-30 Olin Mathieson Radioactive iodinated (i131) fatty material admixed with wax-like material in capsule
US3466361A (en) * 1968-04-18 1969-09-09 Atomic Energy Commission Technetium-99m labeled chelates

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3907846A (en) * 1973-04-12 1975-09-23 Lilly Industries Ltd Preparation of substituted decenoic acids
US4065552A (en) * 1975-05-05 1977-12-27 Giovanni Giacomo Costa Method of detecting malignant neoplasms
DE2947500A1 (de) * 1979-11-24 1981-05-27 Hoechst Ag, 6000 Frankfurt Radiojodierte (omega) -phenylfettsaeuren, ihre herstellung und praeparate zur szintigraphischen untersuchung desherzmuskels und der leber
US4970146A (en) * 1986-01-16 1990-11-13 Havbrukskjemi A/S Method of determining absorbed nutriment in living organisms
US5795561A (en) * 1987-10-23 1998-08-18 The Board Of Regents Of The University Of Michigan Radioiodinated phospholipid ether analogues
US5347030A (en) * 1987-10-23 1994-09-13 The Board Of Regents Of The University Of Michigan Radioiodinated phospholipid ether analogues and methods of using same
US20030215386A1 (en) * 1995-12-01 2003-11-20 Biostream Stereoisomers of fatty acid analogs for diagnostic imaging
EP0869821A4 (en) * 1995-12-01 2002-08-28 David R Elmaleh STEREOISOMERS OF FATTY ACID ANALOGS FOR DIAGNOSTIC IMAGING
WO1997019705A1 (en) * 1995-12-01 1997-06-05 Elmaleh David R Stereoisomers of fatty acid analogs for diagnostic imaging
US7005119B2 (en) 1995-12-01 2006-02-28 Molecular Insight Pharmaceuticals, Inc. Stereoisomers of fatty acid analogs for diagnostic imaging
US20060078495A1 (en) * 1995-12-01 2006-04-13 Molecular Insight Pharmaceuticals, Inc. Stereoisomers of fatty acid analogs for diagnostic imaging
US20070128110A1 (en) * 1995-12-01 2007-06-07 Molecular Insight Pharmaceuticals,Inc. Stereoisomers of fatty acid analogs for diagnostic imaging
EP1767224A3 (en) * 1995-12-01 2007-11-28 Molecular Insight Pharmaceuticals, Inc. Stereoisomers of fatty acid analogs for diagnostic imaging
US7314609B2 (en) 1995-12-01 2008-01-01 Molecular Insight Pharmaceuticals, Inc. Stereoisomers of fatty acid analogs for diagnostic imaging
JP2008201774A (ja) * 1995-12-01 2008-09-04 Molecular Insight Pharmaceuticals Inc 診断用イメージングのための脂肪酸アナログの立体異性体
US20080247948A1 (en) * 1995-12-01 2008-10-09 Molecular Insight Pharmaceuticals, Inc. Stereoisomers of fatty acid analogs for diagnostic imaging
US20060258009A1 (en) * 2003-08-06 2006-11-16 Jandacek Ronald J Use of non-absorbable fat in determining dietary fat absorption
US7695971B2 (en) 2003-08-06 2010-04-13 Children's Hospital Medical Center Use of non-absorbable fat in determining dietary fat absorption

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BE728805A (enrdf_load_stackoverflow) 1969-08-21
GB1263756A (en) 1972-02-16
DE1908804A1 (de) 1969-09-18
NL6802651A (enrdf_load_stackoverflow) 1969-08-26
FR8405M (enrdf_load_stackoverflow) 1971-03-31
JPS518937B1 (enrdf_load_stackoverflow) 1976-03-22
ES363958A1 (es) 1971-01-01
SE348290B (enrdf_load_stackoverflow) 1972-08-28

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