CN1301261C - Diphospho-acid complex of radiative technetium-99m marked oxazole phosphinic acid - Google Patents
Diphospho-acid complex of radiative technetium-99m marked oxazole phosphinic acid Download PDFInfo
- Publication number
- CN1301261C CN1301261C CNB2005100381748A CN200510038174A CN1301261C CN 1301261 C CN1301261 C CN 1301261C CN B2005100381748 A CNB2005100381748 A CN B2005100381748A CN 200510038174 A CN200510038174 A CN 200510038174A CN 1301261 C CN1301261 C CN 1301261C
- Authority
- CN
- China
- Prior art keywords
- technetium
- acid
- labeled
- zoledronic acid
- complex
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention relates to a technetium-99m labeled zoledronic acid type diphosphonic coordination compound and a preparation method thereof, which belongs to the technical field of radioactive drug nuclear medicine. The zoledronic acid type diphosphonic acid specifically comprises 2-(imidazole-1-radical)-1-hydroxy ethane-1, 1-diphosphoric acid(zoledronic acid, ZL), 2-(2-methylimidazole-1-radical)-1-hydroxy ethane-1 and 1-diphosphoric acid (MZL). The preparation method of the coordination compound comprises: a kit is prepared from ligand zoledronic acid type diphosphonic acid (ZL or MZL), a reducing agent, a pH buffering agent, etc.; a pertechnetic acid (<99m>TcO4 <->)solution is added in the kit for reaction to obtain a technetium-99m labeled zoledronic acid type diphosphonic coordination compound <99m>Tc-ZL or<99m>Tc-MZL. The technetium-99m labeled zoledronic acid type diphosphonic acid coordination compound can be used for diagnosing an image in nuclear medicine or be used for treating rheumatoid, tumors, etc.
Description
Technical field
Diphosphonic acid complex of the Zoledronic acid class that radioactivity is technetium-99 m labeled and preparation method thereof the present invention relates to radiopharmaceuticals and the field of nuclear medicine.
Background technology
The main inorganic salt composition of bone is a hydroxyapatite crystal, and its similar ion exchange column has very high surface area, obtains phosphoric acid salt by chemisorption and ion-exchange from blood and usually finishes metabolic turnover with other yuan.Radiopharmaceuticals such as technetium-99m[
99mTc]-be deposited in the bone by hydroxyapatite crystal surface adsorption in the bone rapidly after the phosphonate intravenous injection, show the metabolism situation of bone specifically.When the ill damage of local bone, cause that as inflammation, tumour, fracture etc. regional blood flow and/or the metabolism of bone inorganic salt change, all can show that radioactivity anomaly increases at corresponding site, these are unusual just to have obvious performance in early days usually in disease, adopts technetium-99 m labeled diphosphonate video picture to make early diagnosis and clearly locate various skeletal diseases.Therefore, the bone video picture has obtained a large amount of application in clinical.The video picture of isotropic substance bone can be used for following situation: the early diagnosis that the soft tissue of (1) primary bone tumor and bone tumor and lung shift; (2) check agnogenic ostalgia; (3) select bone histopathologic examination position; (4) formulate radiotherapy planning; (5) reach following up a case by regular visits to after the treatment before the art of other system tumours such as lymphoma, mammary cancer, lung cancer, prostate cancer by stages; (6) the suspected tumor patient is screened; (7) diagnosis of bone inflammatory lesion and following up a case by regular visits to; (8) differential diagnosis of osteoarthrosis such as stress fracture, ischemic osteonecrosis wound; (9) following up a case by regular visits to after the level diagnosis of Paget disease and the treatment.
The radionuclide that is successfully used to the unusual video picture of bone is technetium-99m[
99mTc].Subramanian in 1971 etc. introduce
99mTc polyphosphate marker makes the research of bone iconography tracer agent that very great development arranged.At first be because
99mThe energy of of Tc is 140KeV (energy is moderate), and the transformation period is lacked (transformation period is 6.02h), is suitable for video picture; Secondly, this nucleic is by reactor production, and low price can be promoted the use of.
First success
99mTc mark polyphosphate is
99mTc mark tetra-sodium (
99mTc-PYP), it is the inorganics of band P-O-P key, with hydroxyapatite in the human body bone identical structure is arranged, thereby fast with synosteosis, but this structure is in vivo easily stablized by enzymic hydrolysis inadequately.Further studies show that, the P-O-P key in the tetra-sodium is substituted [being that Sauerstoffatom (O) is replaced with carbon atom (C)] with the P-C-P key obtain
99mThe Diphosphonate of Tc mark has fast with synosteosis in vivo characteristics, is difficult for again by enzymic hydrolysis and more stable.Relatively success be used for clinical bone video picture be technetium-99 m labeled methylene-bis phosphonic acids (
99mTc-MDP), it can be by bone resorption, and active or reactive osseous lesion district concentration is higher at bone metabolism, time of developing is also longer, is the most frequently used skeletal imaging agent at present.Relatively more successful at present technetium-99m (
99mTc) two phosphonic chemical structures of mark are shown in general structure 1.Though
99mTc-MDP is a skeletal imaging agent at present commonly used clinically, and whole body bone localization diagnosis metastatic tumor of bone is highly sensitive in CT, MRI and X ray examination, but specificity is relatively low, therefore, is necessary the further novel diphosphonate skeletal imaging agent of research.
R=CH
2:
99mTc-methylene?diphosphonate(
99mTc-MDP)
R=CH-OH:
99mTc-hydroxymethylene?diphosphonate(
99mTc-HMDP)
R=CH
3-C-OH:
99mTc-hydroxyethylene?diphosphonate(
99mTc-HEDP)
General structure 1
The development of two phosphonic acids (salt) medicine has developed into the three generations so far.The first-generation contains straight chained alkyl or halogen is arranged in the C chain of two phosphonic acids structure P-C-P, is its representative with sodium clodronate (Clodronate), etidronate (Etidronate); The s-generation is introduced terminal amino group in the C chain of two phosphonic acids structure P-C-P, be representative with Sodium Pamidronate (Pamidronate) and alendronate sodium (Alendronate); The characteristics of the two phosphonic acids (salt) of the third generation are for containing the ring-type side chain in the C chain of two phosphonic acids structure P-C-P, with Incadronate (YM175, Incadronate) and Zoledronic acid (Zoledronic Acid) be representative.The diphosphonate drug main in first and second generations will be used as the prevention and treatment of osteoporosis medicine, the diphosphonate medicine of the third generation not only is used as the prevention and treatment of osteoporosis medicine, shifts the pain that causes and hypercalcemia etc. but also be used for the treatment of bone that malignant tumour causes.
Incadronate is the third generation diphosphonate of Japanese Yamanouchi company exploitation, in 1997 in Japan's listing, its preparation specification is that per ampoule contains the 10mg Incadronate, clinical indication is the hypercalcemia that malignant metastatic tumor of bone causes.We have also succeeded in developing and have been used for the treatment of the pain that malignant metastatic tumor of bone causes and " the injection Incadronate " of hypercalcemia.External existing document (Makoto S, Susumu S, HiroshiI.New bone-seeking agent:Animal study of Tc-99m-incadronate.Annals ofNuclear Medicine, 2002; 16:55~59) with the report of technetium-99 m labeled Incadronate as skeletal imaging agent.
U.S. Pat 4939130 (1990) has been reported the two phosphonic acids of multiple imidazoles, one of them, chemistry 2-(imidazoles-1-yl) by name-1-hydroxyl ethane-1, the compound of 1-di 2 ethylhexyl phosphonic acid, be Zoledronic acid (ZoledronicAcid), become at present and be used for the treatment of that bone shifts pain (the Corey E that causes due to hypercalcemia that malignant metastatic tumor of bone causes and multiple myeloma and the solid tumor by company of Switzerland Novartis (Novartist) exploitation, Brown LG, Quinn JE, et al.Zoledronic acid exhibits inhibitory effects onosteoblastic and osteolytic metastases of protate cancer.Clinical CancerResearch, 2003; 9:295~306).But with technetium-99m (
99mTc) mark Zoledronic acid is not all seen any report at present both at home and abroad.
Summary of the invention
The objective of the invention is to propose a kind of novel technetium-99 m labeled two phosphonic acids, the diphosphonic acid complex of promptly technetium-99 m labeled Zoledronic acid class.Simultaneously, the invention allows for the preparation method of the diphosphonic acid complex of technetium-99 m labeled Zoledronic acid class, and they in human or animal's organ or tissue as the purposes of developer, in particular as skeletal imaging agent.
Technical scheme of the present invention:
Two phosphonic acids of Zoledronic acid class, its chemical structure is shown in general structure 2:
General structure 2
R in the general structure 2 represents hydrogen or methyl etc.When R is a Zoledronic acid during for hydrogen, its chemistry 2-(imidazoles-1-yl) by name-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid (English 2-(imidazol-1-yl) by name-1-hydroxyethane-1,1-diphosphonic acid is abbreviated as ZL); When R is methyl, its chemistry 2-(glyoxal ethyline-1-yl) by name-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid (English 2-(2-methylimidazol-1-yl) by name-1-hydroxyethane-1,1-diphosphonic acid is abbreviated as MZL).
The diphosphonic acid complex of technetium-99 m labeled Zoledronic acid class newly provided by the invention, its structural formula is shown in general structure 3.
General structure 3
R wherein is hydrogen or methyl etc.
The preparation method of the diphosphonic acid complex of technetium-99 m labeled Zoledronic acid class is: at first two phosphonic acids and a certain amount of reductive agent, the pH buffer reagent with the Zoledronic acid class is mixed with medicine box, add an amount of high technetium acid solution again, with mixture jolting number minute, promptly obtain the diphosphonic acid complex of technetium-99 m labeled Zoledronic acid class.Reductive agent is tin protochloride (SnCl
2.2H
2O), vitamins C etc.
The diphosphonic acid complex of technetium-99 m labeled Zoledronic acid class can be used for the diagnostic imaging of nuclear medicine, also can be used for the treatment of diseases such as similar rheumatism, tumour.
Beneficial effect of the present invention: the present invention proposes a kind of new two phosphonic acids skeletal imaging agents--diphosphonic acid complex of technetium-99 m labeled Zoledronic acid class, the Zoledronic acid medicine that U.S. Pat 4939130 is reported improves, and comes mark with technetium-99m.Simultaneously, with the technetium-99 m labeled methylene-bis phosphonic acids of document [Liu Liqin etc., Beijing Normal University's journal (natural science edition), 230~233 pages of the 39th the 2nd phases of volume of April in 2003] report (
99mTc-MDP) relatively, the osseous tissue intake (A of product of the present invention
M, bone) (%ID/g) and (A
M, bone/ A
M, blood) than literature value height, illustrate that product of the present invention can be better as the effect of skeletal imaging agent.
Specific embodiments
Embodiment 1
Technetium-99m Zoledronic acid title complex (
99mTc-ZL) preparation and performance measurement thereof
1) preparation of technetium-99m Zoledronic acid title complex
In the 10ml cillin bottle, add Zoledronic acid 3~5mg, SnCl
22H
2(concentration of hydrochloric acid is 1molL to hydrochloric acid soln 0,05~0.2mL of O
-1, include 2.5gL
-1SnCl
22H
2O), shake up the back be adjusted to pH5~7 with phosphate buffer soln (pH8.0), add new drip washing high technetium-99m acid (
99mTcO
4 -) solution 18.5~185 megabecquerels (MBq), abundant mixing, room temperature was placed 5~10 minutes, mark finishes, promptly get technetium-99 m labeled Zoledronic acid title complex of the present invention (
99mTc-ZL).
2) mensuration of technetium-99m Zoledronic acid title complex mark rate
The mark rate of technetium-99m Zoledronic acid title complex is meant that the radioactivity of technetium in the system-99m Zoledronic acid title complex accounts for the per-cent of gross activity.Adopt the HPLC method to measure: adopt U.S. Varian 5000 type HPLC instrument, chromatographic column is the C-18 reversed-phase column, and moving phase is water, and flow velocity is 1.0 milliliters of per minutes.The retention time (Rt) of technetium-99m Zoledronic acid title complex is 1.49 minutes, and the retention time (Rt) of unreacted high technetium-99m acid is 2.39 minutes.The result shows:
99mThe mark rate of Tc-ZL is greater than 95%.
3) mensuration of the vitro stability of technetium-99m Zoledronic acid title complex
Because the transformation period of technetium-99m is 6.02 hours, therefore, freshly prepd technetium-99 m labeled Zoledronic acid title complex is placed room temperature, and different time (1,2,3,4,5 and 6 hour) sampling analysis is investigated technetium-99 m labeled Zoledronic acid title complex shelf stability at room temperature.Experimental result shows: after technetium-99m Zoledronic acid title complex was at room temperature deposited 6 hours, its mark rate and outward appearance had no significant change.Still can satisfy the requirement of clinical application.
4) technetium-99m Zoledronic acid title complex is in the intravital bio distribution of mouse
According among the embodiment 1 1), 2) prepare mark rate greater than 90%
99mTc-ZL solution.(male and female are regardless of with 24 normal mouses, body weight 18~20 grams) be divided into 8 groups at random, from tail vein injection 0.2mL (about 0.80~1.10MBq) technetium-99 m labeled Zoledronic acid complex solution, then respectively at injection back 2,5,10,15,30,60,120 and 180 minutes with the mouse sacrificed by decapitation.Get related organization and organs such as its heart, liver, spleen, lung, kidney, muscle, bone and blood, in trap type gamma ray probe, measure radioactivity after weighing, the radioactivity of calculating every gram tissue accounts for the ratio of the percentage ratio of total injected dose (%ID/g) and bone and the radioactivity of each tissue, and the quality of the whole blood of mouse is calculated by 6.5% of its body weight.Each the time get 3 groups of panel datas mutually, experimental result is represented with mean value.Absorb the amount (A of technetium-99m Zoledronic acid in the different time osseous tissue
M, bone) (%ID/g) be respectively 5.41,5.51,7.08,10.40,13.45,9.78,10.05 and 8.55; Amount (the A of technetium in the different time blood-99m Zoledronic acid
M, blood) (%ID/g) be respectively 13.78,4.54,2.13,1.49,0.79,0.42,0.35, O.17; A
M, bone/ A
M, bloodBe respectively 0.39,1.21,3.33,6.98,17.03,23.29,28.71 and 50.29.
Embodiment 2
Technetium-99 m labeled 2-(glyoxal ethyline-1-yl)-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid title complex (
99mTc-MZL) preparation and performance measurement thereof
1)
99mThe preparation of Tc-MZL
In the 10ml cillin bottle, add 2-(glyoxal ethyline-1-yl)-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid 3~5mg, SnCl
22H
2(concentration of hydrochloric acid is 1molL to hydrochloric acid soln 0.05~0.2mL of O
-1, include 2.5gL
-1SnCl
22H
2O), shake up the back be adjusted to pH5~7 with phosphate buffer soln (pH8.0), add new drip washing high technetium-99m acid (
99mTcO
4 -) solution 18.5~185 megabecquerels (MBq), abundant mixing, room temperature was placed 5~10 minutes, promptly got technetium-99 m labeled 2-of the present invention (glyoxal ethyline-1-yl)-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid title complex (
99mTc-MZL).
2)
99mThe mensuration of Tc-MZL mark rate
Adopt the HPLC method to measure: adopt U.S. Varian 5000 type HPLC instrument, chromatographic column is the C-18 reversed-phase column, and moving phase is V (w=25% ammoniacal liquor)/V (water)=1/9, and flow velocity is 1.0 milliliters of per minutes.
99mThe retention time of Tc-MZL (Rt) is 1.39 minutes, unreacted high technetium-99m acid (
99mTcO
4 -) retention time (Rt) be 2.41 minutes.The result shows:
99mThe mark rate of Tc-MZL is greater than 95%.
3)
99mThe mensuration of the vitro stability of Tc-MZL
Because the transformation period of technetium-99m is 6.02 hours, therefore, with freshly prepd 9
9mTc-MZL places room temperature, and different time (1,2,3,4,5 and 6 hour) sampling analysis is investigated
99mTc-MZL shelf stability at room temperature.Experimental result shows:
99mAfter Tc-MZL at room temperature deposited 6 hours, its mark rate and outward appearance had no significant change.
4)
99mTc-MZL is in the intravital bio distribution of mouse
According among the embodiment 2 1), 2) prepare mark rate greater than 90%
99mTc-MZL solution.24 normal mouses (male and female are regardless of, body weight 18~20 grams) are divided into 8 groups at random, from tail vein injection 0.2mL (about 0.80~1.10MBq)
99mTc-MZL solution is then respectively at injecting back 2,5,10,15,30,60,120 and 180 minutes with the mouse sacrificed by decapitation.Get related organization and organs such as its heart, liver, spleen, lung, kidney, muscle, bone and blood, in trap type gamma ray probe, measure radioactivity after weighing, the radioactivity of calculating every gram tissue accounts for the ratio of the percentage ratio of total injected dose (%ID/g) and bone and the radioactivity of each tissue, and the quality of the whole blood of mouse is calculated by 6.5% of its body weight.Each the time get 3 groups of panel datas mutually, experimental result is represented with mean value.Absorb in the different time osseous tissue
99mAmount (the A of Tc-MZL
M, bone) (%ID/g) be respectively 13.28,14.30,13.08,11.78,8.50,7.95,11.29,13.88; In the different time blood
99mAmount (the A of Tc-MZL
M, blood) (%ID/g) be respectively 15.73,6.18,3.49,2.54,0.69,0.34,0.145,0.099; A
M. bone/ A
M. bloodBe respectively 0.84,2.31,3.75,4.64,12.32,23.38,77.86,140.20.
And the technetium-99 m labeled methylene-bis phosphonic acids of document [Liu Liqin etc., Beijing Normal University's journal (natural science edition), 230~233 pages of the 39th the 2nd phases of volume of April in 2003] report (
99mTc-MDP) amount (A that absorbs in the osseous tissue when 30 minutes, 60 minutes, 120 minutes and 180 minutes
M, bone) (%ID/g) be respectively 3.26,4.79,3.87,7.71; In the different time blood
99mAmount (the A of Tc-MDP
M, blood) (%ID/g) be respectively 0.47,0.28,0.15,0.12; A
M, bone/ A
M, bloodBe respectively 6.91,17.31,26.22,67.34.
Claims (6)
2, the diphosphonic acid complex of the technetium-99 m labeled Zoledronic acid class of radioactivity according to claim 1, when wherein R is hydrogen, its chemistry technetium-99 m labeled 2-(imidazoles-1-yl)-1-hydroxyl ethane-1 by name, 1-di 2 ethylhexyl phosphonic acid title complex is abbreviated as
99mTc-ZL.
3. the diphosphonic acid complex of the Zoledronic acid class that radioactivity according to claim 1 is technetium-99 m labeled, when wherein R is methyl, its chemistry technetium-99 m labeled 2-(glyoxal ethyline-1-yl)-1-hydroxyl ethane-1 by name, 1-di 2 ethylhexyl phosphonic acid title complex is abbreviated as
99mTc-MZL.
4. the preparation method of the diphosphonic acid complex of the Zoledronic acid class that radioactivity as claimed in claim 1 is technetium-99 m labeled is characterized in that this method is: in cillin bottle, add two phosphonic acids 3~5mg of Zoledronic acid class, adding concentration of hydrochloric acid again is 1molL
-1, include 2.5gL
-1SnCl
2.2H
2Hydrochloric acid soln 0.05~0.2mL of O, phosphate buffer soln with pH8.0 after shaking up is adjusted to pH5~7, high technetium-99m acid solution 18.5-185 the megabecquerel that adds new drip washing, abundant mixing, room temperature was placed 5~10 minutes, promptly obtained the diphosphonic acid complex of described technetium-99 m labeled Zoledronic acid class.
5. the preparation method of the diphosphonic acid complex of the Zoledronic acid class that radioactivity according to claim 4 is technetium-99 m labeled, the two phosphonic acids that it is characterized in that Zoledronic acid class used in this method are Zoledronic acid, then prepare technetium-99 m labeled 2-as claimed in claim 2 (imidazoles-1-yl)-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid title complex.
6. the preparation method of the diphosphonic acid complex of the Zoledronic acid class that radioactivity according to claim 4 is technetium-99 m labeled, the two phosphonic acids that it is characterized in that Zoledronic acid class used in this method are 2-(glyoxal ethyline-1-yl)-1-hydroxyl ethane-1, the 1-di 2 ethylhexyl phosphonic acid, then prepare technetium-99 m labeled 2-as claimed in claim 3 (glyoxal ethyline-1-yl)-1-hydroxyl ethane-1,1-di 2 ethylhexyl phosphonic acid title complex.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2005100381748A CN1301261C (en) | 2005-01-18 | 2005-01-18 | Diphospho-acid complex of radiative technetium-99m marked oxazole phosphinic acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2005100381748A CN1301261C (en) | 2005-01-18 | 2005-01-18 | Diphospho-acid complex of radiative technetium-99m marked oxazole phosphinic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1680409A CN1680409A (en) | 2005-10-12 |
CN1301261C true CN1301261C (en) | 2007-02-21 |
Family
ID=35067210
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2005100381748A Expired - Fee Related CN1301261C (en) | 2005-01-18 | 2005-01-18 | Diphospho-acid complex of radiative technetium-99m marked oxazole phosphinic acid |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1301261C (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101985456B (en) * | 2010-07-02 | 2012-05-16 | 江苏省原子医学研究所 | Bone-seeking 99mTc-IPrDP coordination compound as well as preparation method and application thereof |
CN111166898B (en) * | 2020-02-21 | 2022-09-02 | 上海市第十人民医院 | Technetium [ alpha ] 99 Tc]Application of zoledronic acid in preparation of medicine for treating osteoporosis |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1102125A (en) * | 1993-10-30 | 1995-05-03 | 陶燃 | Medicine using trace element technetium as active component |
US6267936B1 (en) * | 1996-09-30 | 2001-07-31 | Basf Aktiengesellschaft | Method for effecting solvent extraction of metal ions using hydrocarbon soluble aminomethylene phosphonic acid compounds |
-
2005
- 2005-01-18 CN CNB2005100381748A patent/CN1301261C/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1102125A (en) * | 1993-10-30 | 1995-05-03 | 陶燃 | Medicine using trace element technetium as active component |
US6267936B1 (en) * | 1996-09-30 | 2001-07-31 | Basf Aktiengesellschaft | Method for effecting solvent extraction of metal ions using hydrocarbon soluble aminomethylene phosphonic acid compounds |
Also Published As
Publication number | Publication date |
---|---|
CN1680409A (en) | 2005-10-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Palma et al. | Bisphosphonates as radionuclide carriers for imaging or systemic therapy | |
Neves et al. | Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies | |
CN107106711A (en) | Conjugation diphosphonate for diagnosing and treating osteopathy | |
AU657641B2 (en) | Macrocyclic aminophosphonic acid complexes, their preparation, formulations and use | |
Lin et al. | Preparation and preclinical pharmacological study on a novel bone imaging agent 99mTc-EMIDP | |
Ogawa et al. | Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent | |
Lin et al. | Preparation and in vivo biological investigations on a novel radioligand for bone scanning: technetium-99m-labeled zoledronic acid derivative | |
Lin et al. | Development of superior bone scintigraphic agent from a series of 99mTc-labeled zoledronic acid derivatives | |
Wang et al. | Animal studies of 99mTc–i-PIDP: A new bone imaging agent | |
CN1301261C (en) | Diphospho-acid complex of radiative technetium-99m marked oxazole phosphinic acid | |
Xu et al. | Radiolabeling, quality control, biodistribution, and imaging studies of 177Lu‐ibandronate | |
CN101985456B (en) | Bone-seeking 99mTc-IPrDP coordination compound as well as preparation method and application thereof | |
Mirković et al. | Investigation of 177Lu-labeled HEDP, DPD, and IDP as potential bone pain palliation agents | |
CN100469781C (en) | Double phospho acid compound of 99mT.C. mark and preparation method | |
Banerjee et al. | Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models | |
Kodina et al. | Osteotropic radiopharmaceuticals in Russian nuclear medicine techniques | |
CN101693724A (en) | Technetium-99m labeled propyl zoledronic acid composition and preparation method thereof | |
CN101250201A (en) | Technetium-99m marked triazole diphosphonic acid complex and preparation method thereof | |
Chauhan et al. | 68Ga-Labeled bismacrocyclic methylene phosphonate as potential bone seeking PET radiopharmaceutical | |
Xu et al. | A study on the preparation, evaluation of biological characteristics, and preliminary imaging of [188Re] Re-ibandronate | |
CN1418884A (en) | 99TcMN dimercaptosuccinate compound, its preparation process and application in nucleic medicine science | |
CN101130555B (en) | **TC*N nucleus marked dithiocarbamate complex, preparing method and application of the same | |
Qiu et al. | A Novel 99mTc-labeled Diphosphonic Acid as Potential Bone Seeking Agent: Synthesis and Biological Evaluation | |
CN1260234C (en) | Diphosphonic acid derivative, 99 mTc labelled diphos phonic acid derivative and its application | |
Nikzad et al. | Development and assessment of 153Sm-zoledronate complex as a possible bone pain palliative agent |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |