WO1999020316A1 - Radiotraceurs d'emission monophotonique et leurs methodes d'utilisation - Google Patents

Radiotraceurs d'emission monophotonique et leurs methodes d'utilisation Download PDF

Info

Publication number
WO1999020316A1
WO1999020316A1 PCT/US1998/021954 US9821954W WO9920316A1 WO 1999020316 A1 WO1999020316 A1 WO 1999020316A1 US 9821954 W US9821954 W US 9821954W WO 9920316 A1 WO9920316 A1 WO 9920316A1
Authority
WO
WIPO (PCT)
Prior art keywords
single photon
group
compound
γçö
emitting
Prior art date
Application number
PCT/US1998/021954
Other languages
English (en)
Inventor
Padmakar V. Kulkarni
Michael D. Devous, Sr.
Original Assignee
Board Of Regents, The University Of Texas System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Board Of Regents, The University Of Texas System filed Critical Board Of Regents, The University Of Texas System
Priority to AU98073/98A priority Critical patent/AU9807398A/en
Publication of WO1999020316A1 publication Critical patent/WO1999020316A1/fr

Links

Classifications

    • 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
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers

Definitions

  • the present invention relates to compounds that can be used to study glucose metabolism in a living subject, and to thereby aid in the diagnosis and/or treatment of the subject.
  • SPECT Single photon emission computed tomography
  • an appropriate substrate or substrate analog has to be chosen.
  • the particular compounds must be transported and metabolized via the same reactions and at the same rate as the natural substrate.
  • Glucose analogs labeled with positron-emitting radionuclides have been synthesized and tested for in vivo measurements using positron emission tomography (PET).
  • PET positron emission tomography
  • the substrate most commonly used is 2- F-2-deoxy-D-glucose (FDG).
  • FDG 2- F-2-deoxy-D-glucose
  • positron emitters have serious limitations due to their short half-lives, which require an on-site cyclotron at the location where they will be used.
  • PET is relatively expensive and is available in a relatively limited number of locations.
  • Single photon imaging devices, in contrast to PET, are more widely available and far less expensive. Thus single photon imaging tracers are easier to apply clinically. Further, SPECT tracers can receive approval by the U.S.
  • Radioactive iodine is another radionuclide of interest, and offers some potential advantages over m Tc.
  • the chemistry of iodine is better defined than that of technetium, and I has suitable characteristics for SPECT imaging studies.
  • radioiodinated agents can complement brain blood flow studies that use m Tc-labeled agents, by taking advantage of dual isotope techniques which permit simultaneous imaging of m Tc and
  • the present invention concerns radiation-emitting compounds that comprise:
  • a radiation-emitting moiety that is selected from the group consisting of (i) a heterocyclic group having about 3-12 carbon atoms, labeled with a radionuclide, (ii) a
  • the radinuclide is one preferred embodiment of the invention is a single photon-emitting
  • radionuclide In another embodiment, the radionuclide is a beta emitter.
  • the radiation-emitting moiety is preferably covalently bonded to the glucose or glucose derivative.
  • a suitable glucose derivative is D-glucosamine.
  • the substrate (a) is preferably glucose rather than a derivative thereof such as glucosamine.
  • the substrate (a) is preferably glucosamine.
  • the compound comprises a glucose derivative having the formula
  • Rj is selected from the group consisting of hydrogen, hydroxyl, and OR 7 ; where one of R 3 , R 4 , R 5 , and R 6 is the single photon-emitting moiety, and the rest of R 3 , R 4 , R 5 , and R 6 are selected from the group consisting of hydrogen, hydroxyl, and OR 7 ; and where R 7 is an aliphatic hydrocarbon having from 1-4 carbon atoms.
  • the single photon-emitting moiety can optionally comprise a linker moiety that is covalently bonded to the substrate.
  • the single photon-emitting moiety can be selected from the group consisting of radiolabeled derivatives of:
  • X is halogen or hydroxyl
  • n is an integer from 0-4
  • L is a linker moiety selected from the group consisting of — O(CH 2 ) a — , — NH(CH 2 ) a ⁇ , — OCONH(CH 2 ) b — , and
  • a is from 1-6 and b is from 0-6, with a preferably being 1 or 2 and b preferably being 0-1.
  • the radionuclide used in compounds of the present invention preferably is selected from t .,he group consi •st .i.ng of r- 123 ⁇ I, 125 ⁇ I, 131 ⁇ I, 9 ⁇ 1 ⁇ Tc, 186 ⁇ Re, and , 188r R>e.
  • One specific embodiment of the invention is a glucose or glucose derivative (e.g., glucosamine) that is attached to a thiocarbamate compound that comprises 1 -4 SH groups and 2-
  • Such a thiocarbamate glucose derivative chelating m Tc, Re, or Re is one preferred embodiment of the invention.
  • One specific example of this embodiment of the invention is m Tc labeled N-methyl glucamine dithiocarbamate.
  • Another aspect of the invention concerns a method of imaging an internal portion of a living subject. This method comprises (a) administering internally to a living subject an amount effective to generate a SPECT image of a compound as described above, and (b) performing a
  • Another aspect of the invention is a method of providing radiation treatment to a living subject, especially a human, in which a therapeutically effective amount of a compound as described above is administered internally to the subject.
  • the radionuclide comprised in the compound can itself provide a therapeutic dose of radiation to the subject (e.g., enough radiation to kill tumor cells) as well as permitting the generation of an adequate SPECT image, then the compound can serve the dual purposes of irradiating tissue in the subject for therapeutic effect and simultaneously generating an image of the relevant part of the body.
  • One additional aspect of the invention concerns a pharmaceutical composition for use in SPECT procedures, which comprises a pharmaceutically acceptable carrier and a compound as described above.
  • the compounds of the present invention comprise units that would be recognized by human cells (normal organs, pathologically damaged organs, or tumors) as substrates for metabolism.
  • Compounds of the present invention can be used internally in humans due to their chemical and biological stability.
  • the compounds and methods of the present invention can be used to diagnose and treat human patients, based on the localization of the compounds through metabolic pathways and the emissions of the radiotracer for imaging or therapy.
  • the compounds can be used in single photon metabolic imaging, permitting relatively inexpensive diagnosis and management of brain (e.g., psychiatric and neurologic disorders), cardiac, and oncologic disorders which in the past could only be imaged with PET.
  • Figs. 1-11 are graphs of the biodistribution of compounds of the present invention at various times after injection in animals, as explained further in Examples 1 and 2, below.
  • Table 1 below provides compound reference numbers for the some of the compounds of the present invention that are discussed in the examples or figures.
  • Compounds in accordance with the present invention generally are comprised of a human metabolic substrate such as glucose or a glucose derivative, to which is bonded a moiety that is radiolabeled with a single photon-emitting radionuclide, such as radioactive iodine, technetium, or rhenium.
  • a linker moiety optionally can be interposed between the metabolic substrate and the radiolabeled moiety. Alternatively, the linker moiety can itself be radiolabeled. Examples of compounds which can be radiolabeled for use in the methods of the present invention are as follows.
  • the radionuclide will be preferably provided in the compound by means of, e.g., a radioisotopic exchange reaction, in which the radionuclide is substituted for an, e.g., hydrogen, halogen, or alkali metal atom, or a hydroxyl group.
  • R is as described above.
  • the crystal was hydrolyzed by 20 ml of IN H 2 SO 4 in 8 ml ethanol, boiling for 2 hours. The solution was cooled and neutralized with Ba(OH) 2 solution. The BaSO 4 was filtered and the filtrate was concentrated to dryness in a vacuum. A syrup was obtained.
  • the product was separated with thin layer chromatography (TLC), and washed down by methanol. The solution was concentrated to dryness in a vacuum and a syrup was obtained. The syrup was changed into solid under high vacuum.
  • TLC thin layer chromatography
  • Step 1 Synthesis of 3-O-(m-iodobenzyl)- 1 ,2,5,6-diisopropylidene-D-glucose (A)
  • Step 1 3,4,6-Tri-O-acetyl-piperidine-N-D-glucoside (C)
  • Glucosamine hydrochloride (1.0 g; 0.0046 mol) was dissolved in 1 N NaOH solution (4.6 ml). After adding 0.63 g of p-anisaldehyde (0.0046 mol) into this mixture, the solution was stirred for 3 h. at room temperature and subsequently left standing for 30 min at 0°C. The collected crude product was first washed with cold water followed by a mixture of ethanol : ether (1 : 1). The obtained crystals dried in a desiccator, were used in the next stage of the synthetic process. Yield: 1.09 g, 81%.
  • Step 2 N-(4'-methoxybenzyden)- 1 ,3 ,4,6-tetra-O-acetyl-glucosamine (F)
  • Step 3 1,3,4,6-tetra-O-acetyl-glucosamine (G) Having dissolved 5.0 g (0.01 mol) of compound (F) in acetone (25 ml), concentrated HC1 (1 ml) was added prior to letting the mixture stand for 5 min. The collected crystals were washed with cold ether, resuspended in 2 M sodium acetate solution (50 ml) and thereafter extracted by chloroform (4 x 50 ml). The chloroform layer was decanted, dried with sodium sulfate and evaporated to dryness in vacuo. The obtained crystals were recrystallized from ether. Yield: 1.9 g, 55%.
  • Step 4 N-(4'-iodobenzoyl)- 1 ,3 ,4,6-tetra-O-acetyl-glucosamine (H)
  • Glucosamine hydrochloride 2.15g (0.01 mol) and sodium bicarbonate 1.05g (0.012 mol) were dissolved in 20 ml of water, and sahcylaldehyde 1.1 ml (0.01 mol) added. The mixture was stirred vigorously at the room temperature, and in 30 min, crystal formation commenced. Stirring was continued for three and half hours, then the crystals were filtered, washed with cold water, and recrystallized from methyl alcohol. A bright yellow needle crystal was obtained.
  • the product (1.3 g) was dissolved in 10 ml of DMSO and 10 ml of methanol, then sodium borohydride (81 mg; 0.0022 mmol) was added. The mixture was stirred 2 h. under nitrogen at room temperature.
  • This compound was found to be air sensitive, and therefore could not be radiolabeled.
  • One embodiment of the present invention involves radiotracer compounds which include Technetium-99m. Preparation of such compounds can be done by the following three steps: (1) The first step involves the synthesis of bifunctional chelating agent (BCA) containing N 2 S 2 ligand along with and functional group needed for binding a biological active molecule. (2) The second step involves the attachment of the above bifunctional chelating agent (BCA) to glucose molecule (or glucosamine) in which some of the functional hydroxyl groups are selectively protected. (3) The third step involves the deprotection of the functional groups and technetium labeling.
  • BCA bifunctional chelating agent
  • D-glucose, p-toluidine, N-methyl-D-glucamine, carbon disulfide, and sodium hydroxide were obtained from Aldrich Chemical Company.
  • Sodium hydroxide (20 gm, 0.5 mol) was dissolved in 200 ml of water and N-methylglucamine (97.6 gm) was added to it. The mixture was stirred with a magnetic stirrer. The resulting clear solution was cooled in an ice bath and a solution of carbon disulfide (50 ml) in 100 ml absolute ethanol was added slowly with continuous stirring. The temperature of the reaction mixture was kept between 0-5°C during the addition of carbon disulfide.
  • the compound is believed to chelate Tc, thus allowing the complex to function as a biocompatible radiotracer in vivo.
  • the present invention can be further understood from the following examples.
  • Compound 3 showed 0.15% uptake at one min., which slowly declined to 0.1% by 45 min. after injection. These compounds also showed not inconsequential myocardial uptake (3% injected dose/gram which declined slowly to 2.5% by 45 minutes). This suggests that these compounds could be used as myocardial glucose imaging agents as well as brain imaging agents. Blood activity was initially high (1 1% for compound 1 and 7% for both compounds 2 and 3) but declined to 4-7% by 15 minutes and to 3-5% by 45 minutes. As a consequence, the brain-to-blood ratios, an important indicator of the ability to image these compounds, steadily increased for compounds 1 and 2 and remained reasonably constant for compound 3. (See Figs. 4 and 5.) All three compounds had a brain-to-blood ratio in excess of 3 at 45 minutes after injection. Of the three compounds, compound 1 showed the highest brain uptake at 45 minutes and the most stable distribution over time.
  • Compound 4 appeared to be the most promising of the three.
  • the two-minute images it provided were clearly superior to those at later times. Virtually no blood pool activity was seen, and appropriate structural delineation was observed.
  • the 15 minute images showed loss of structural detail, which further degraded by the time of the 45 minute images.
  • autoradiographic images with this compound showed no structural detail at any time post- injection, and on a second occasion, structural detail was minimal.
  • the %ID/g and %ID/organ were significantly higher at 2 minutes post-injection for compound 4 than for the other two compounds, but by 15 and 45 minutes post-injection, uptake was not different among the three. Uptake in heart or blood was not different at any time among the three compounds.
  • Compound 7 provided intermittent results. On two occasions, some structural detail was observed that did not degrade at all over time. However, on two other occasions little detail was observable at any time period even though the biodistribution (% uptake) was not different among these experiments. The explanation for these inconsistencies is not presently known.
  • compositions of the present invention are preferably formulated with a pharmaceutically acceptable carrier, such as sterile water or saline solution, such that the composition will be biocompatible and suitable for internal administration to a human, or other mammal.
  • a pharmaceutically acceptable carrier such as sterile water or saline solution
  • other pharmaceutically acceptable materials including biologically active agents, could be included in the composition as well.
  • compositions are preferably administered internally to a living subject by intravenous injection, but other methods of administration, such as oral or intra-arterial administration, could also be used.
  • concentration of the compound in an aqueous formulation can vary, but can suitably be between about 0.1% and about 10% by weight.
  • the amount administered to a living subject in order to perform a SPECT imaging procedure will also vary, but is preferably between about 0.1-30 mCi, most preferably between about 3-30 mCi.
  • an intravenous bolus of the composition is administered to the patient and photon emissions from the patient or a region thereof are monitored for a period of time.
  • the SPECT procedure can be performed in a fashion that is known to those skilled in this field. Suitable SPECT equipment is well known in the field, and examples include those disclosed in Michael D. Devous, Sr., "SPECT Functional Brain Imaging,” in Clinical SPECT Imaging, pp. 97-128 (E.L. Kramer and J. J. Sanger, eds.) (Raven Press 1995).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Une partie interne d'un sujet vivant peut être reproduite en image par: (a) administration par voie interne au patient vivant d'une dose efficace pour produire une image SPECT (tomographie d'émission monophotonique) d'un composé d'émission monophotonique, le composé comprenant (i) du glucose ou un dérivé du glucose constituant un substrat pour un processus métabolique humain et (ii) une fraction d'émission monophotonique choisie dans le groupe comprenant (A) un groupe hétérocyclique ayant environ 3 à 12 atomes de carbone, marqué par un radionucléide d'émission monophotonique, (B) un groupe hydrocarbure ayant environ 3 à 12 atomes de carbone, marqué par un radionucléide d'émission monophotonique allylique, (C) un groupe thio marqué par un radionucléide d'émission monophotonique, (D) un groupe aromatique ayant environ 6 à 12 atomes de carbone, marqué par un radionucléide d'émission monophotonique, et (E) un groupe hydrocarbure ayant environ 3 à 12 atomes de carbone, marqué par un radionucléide d'émission monophotonique vinylique; et (B) exécution d'une procédure SPECT sur le sujet afin de détecter les photons émis par le composé, produisant ainsi une image SPECT d'une partie interne du sujet. Des compositions et des méthodes thérapeutiques sont également décrites.
PCT/US1998/021954 1997-10-20 1998-10-16 Radiotraceurs d'emission monophotonique et leurs methodes d'utilisation WO1999020316A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU98073/98A AU9807398A (en) 1997-10-20 1998-10-16 Single photon-emitting radiotraces and methods for their use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US95422397A 1997-10-20 1997-10-20
US08/954,223 1997-10-20

Publications (1)

Publication Number Publication Date
WO1999020316A1 true WO1999020316A1 (fr) 1999-04-29

Family

ID=25495119

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/021954 WO1999020316A1 (fr) 1997-10-20 1998-10-16 Radiotraceurs d'emission monophotonique et leurs methodes d'utilisation

Country Status (2)

Country Link
AU (1) AU9807398A (fr)
WO (1) WO1999020316A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001054734A2 (fr) * 2000-01-28 2001-08-02 Molypharma, S.A. Produit radiopharmaceutique utilise en therapie tumorale radio-isotopique
WO2003082301A1 (fr) * 2002-03-29 2003-10-09 Threshold Pharmaceuticals, Inc. Compositions et methodes pour le traitement du cancer
US6989140B2 (en) 2001-12-21 2006-01-24 Threshold Pharmaceuticals, Inc. Methods for cancer imaging
JP2008531755A (ja) * 2005-01-05 2008-08-14 ボード オブ リージェンツ， ザ ユニバーシティ オブ テキサス システム 二重画像化および放射線化学療法のためのコンジュゲート：組成物、製造および適応
US7560230B2 (en) 2003-03-07 2009-07-14 Threshold Pharmaceuticals, Inc. Method for determining susceptibility of tumor to treatment with anti-neoplastic agent
WO2016052488A1 (fr) * 2014-09-29 2016-04-07 株式会社ダステック Composé chélate et son procédé de production
CN106565797A (zh) * 2016-10-18 2017-04-19 浙江工业大学 一种葡萄糖酰胺类化合物及其制备与应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0074429A1 (fr) * 1981-09-16 1983-03-23 Nihon Medi-Physics Co., Ltd. Agent de diagnostic radioactif et sa préparation
US4789542A (en) * 1986-04-29 1988-12-06 The United States Of America As Represented By The United States Department Of Energy Radioiodinated glucose analogues for use as imaging agents
US4826966A (en) * 1986-04-29 1989-05-02 The United States Of America As Represented By The United States Department Of Energy Radioiodinated branched carbohydrates
EP0413145A1 (fr) * 1989-07-13 1991-02-20 Nihon Medi-Physics Co., Ltd. Agent diagnostique radioactif
WO1996034872A1 (fr) * 1995-05-02 1996-11-07 Cis Bio International Derives iodes de monosaccharides utilisables comme produits radiopharmaceutiques
WO1997007829A1 (fr) * 1995-08-23 1997-03-06 University Advanced Bio-Imaging Associates Nouveaux agents de contraste et leur procede de preparation et d'utilisation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0074429A1 (fr) * 1981-09-16 1983-03-23 Nihon Medi-Physics Co., Ltd. Agent de diagnostic radioactif et sa préparation
US4789542A (en) * 1986-04-29 1988-12-06 The United States Of America As Represented By The United States Department Of Energy Radioiodinated glucose analogues for use as imaging agents
US4826966A (en) * 1986-04-29 1989-05-02 The United States Of America As Represented By The United States Department Of Energy Radioiodinated branched carbohydrates
EP0413145A1 (fr) * 1989-07-13 1991-02-20 Nihon Medi-Physics Co., Ltd. Agent diagnostique radioactif
WO1996034872A1 (fr) * 1995-05-02 1996-11-07 Cis Bio International Derives iodes de monosaccharides utilisables comme produits radiopharmaceutiques
WO1997007829A1 (fr) * 1995-08-23 1997-03-06 University Advanced Bio-Imaging Associates Nouveaux agents de contraste et leur procede de preparation et d'utilisation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GOODMAN M M ET AL: "SYNTHESIS OF 4-O-(E)-IODOPROPENYL GLUCOSE AS A POTENTIAL BRAIN AND HEART IMAGING AGENT", JOURNAL OF NUCLEAR MEDICINE, vol. 30, no. 11, 1 November 1989 (1989-11-01), pages 3AB, XP000069668 *
J. E. BISKUPIK ET AL.: "Synthesis of an (iodovinyl)misonidazole Derivative for hypoxia imaging.", JOURNAL OF MEDICINAL CHEMISTRY, vol. 34, 1991, WASHINGTON US, pages 2165 - 2168, XP002091797 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001054734A2 (fr) * 2000-01-28 2001-08-02 Molypharma, S.A. Produit radiopharmaceutique utilise en therapie tumorale radio-isotopique
WO2001054734A3 (fr) * 2000-01-28 2001-12-06 Molypharma S A Produit radiopharmaceutique utilise en therapie tumorale radio-isotopique
US6989140B2 (en) 2001-12-21 2006-01-24 Threshold Pharmaceuticals, Inc. Methods for cancer imaging
WO2003082301A1 (fr) * 2002-03-29 2003-10-09 Threshold Pharmaceuticals, Inc. Compositions et methodes pour le traitement du cancer
US7001888B2 (en) 2002-03-29 2006-02-21 Threshold Pharmaceuticals, Inc. Compositions and methods for treating cancer
US7560230B2 (en) 2003-03-07 2009-07-14 Threshold Pharmaceuticals, Inc. Method for determining susceptibility of tumor to treatment with anti-neoplastic agent
JP2008531755A (ja) * 2005-01-05 2008-08-14 ボード オブ リージェンツ， ザ ユニバーシティ オブ テキサス システム 二重画像化および放射線化学療法のためのコンジュゲート：組成物、製造および適応
WO2016052488A1 (fr) * 2014-09-29 2016-04-07 株式会社ダステック Composé chélate et son procédé de production
JP2016069467A (ja) * 2014-09-29 2016-05-09 株式会社ダステック キレート化合物及びその製造方法
CN106565797A (zh) * 2016-10-18 2017-04-19 浙江工业大学 一种葡萄糖酰胺类化合物及其制备与应用
CN106565797B (zh) * 2016-10-18 2019-06-14 浙江工业大学 一种葡萄糖酰胺类化合物及其制备与应用

Also Published As

Publication number Publication date
AU9807398A (en) 1999-05-10

Similar Documents

Publication Publication Date Title
KR910006978B1 (ko) 에스테르-치환된 디아민디티올
EP1698350B1 (fr) Composés à base de porphyrine pour des applications dans l'imagerie des tumeurs et en thérapie photodynamique
EP2341944B1 (fr) Conjuguées de hexose et de composées coordinand des métaux pour utilisation dans l'imagerie
CN117159753A (zh) 放射性标记的伊文思蓝衍生物药物的制备方法及用途
WO2008024830A2 (fr) Halogénoimatinibes radiomarqués et leurs procédés de synthèse et d'utilisation dans l'imagerie par tep de cancers
WO1999020316A1 (fr) Radiotraceurs d'emission monophotonique et leurs methodes d'utilisation
AU633597B2 (en) 99m tc(iii) myocardial imaging agents that are effective in humans
US20170334804A1 (en) F-18 labeled tracer and methods of manufacture
EP3721907B1 (fr) Dérivés d'inhibiteur de psma pour l'étiquetage au 99mtc via hynic, kit radiopharmaceutique, préparations radiopharmaceutiques et leur utilisation dans le diagnostic du cancer de la prostate
KR101191649B1 (ko) 이작용기성 테트라아자 거대고리 화합물의 제조방법 및 용도
JPH03264599A (ja) 組織ヒポキシアの新標識剤
KR101130737B1 (ko) 방사성 세포 표지자
CA1337986C (fr) Ether-oxyde de dihematoporphyrine marque par un isotope et son emploi pour la detection et le traitement de tissus neoplastiques
US4781912A (en) Cationic complex of technetium-99m.
US8198432B2 (en) Porphyrin-based compounds for tumor imaging and photodynamic therapy
WO2006121035A1 (fr) Procede de production d’un compose organique marque avec un halogene radioactif
JPH09176179A (ja) グルコースまたはマンノース誘導体、および該誘導体を含有する放射性診断剤
EP4382137A1 (fr) Nouveau composé comprenant un groupe ester et ses utilisations
CN101486707A (zh) 2-甲基-5-硝基咪唑类化合物及其制备方法和应用
US6165441A (en) Method of diagnosis and photodynamic therapy of tumours
Jalilian et al. No‐carrier‐added, 18F‐labelling of a cholesterol derivative, used in detection of adrenal malignancies
CN116987128A (zh) 一种含(D)-α-亚氨基酸修饰的甘露糖衍生物及其应用
KR920002167B1 (ko) 에스테르-치환된 디아민디티올을 포함하는 키트 및 방사성 약제
JPH03261786A (ja) ポルフィリン金属複合体とその用途
CN114853827A (zh) 一种葡萄糖衍生配体化合物及其制备方法和应用

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: CA

122 Ep: pct application non-entry in european phase