CN106110343A - PET tracer of one species-specific diagnosis melanoma and preparation method thereof - Google Patents

PET tracer of one species-specific diagnosis melanoma and preparation method thereof Download PDF

Info

Publication number
CN106110343A
CN106110343A CN201610539882.8A CN201610539882A CN106110343A CN 106110343 A CN106110343 A CN 106110343A CN 201610539882 A CN201610539882 A CN 201610539882A CN 106110343 A CN106110343 A CN 106110343A
Authority
CN
China
Prior art keywords
melan
antibody
ncs
melanoma
pet
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.)
Pending
Application number
CN201610539882.8A
Other languages
Chinese (zh)
Inventor
李爱梅
林夏雯
郭爱斌
张炜
汪彦扬
谭千倩
陈德柱
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing Drum Tower Hospital
Original Assignee
Nanjing Drum Tower Hospital
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 Nanjing Drum Tower Hospital filed Critical Nanjing Drum Tower Hospital
Priority to CN201610539882.8A priority Critical patent/CN106110343A/en
Publication of CN106110343A publication Critical patent/CN106110343A/en
Pending legal-status Critical Current

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
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Immunology (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)
  • Peptides Or Proteins (AREA)

Abstract

The invention discloses the PET tracer of a species-specific diagnosis melanoma, use difunctional improvement chelating agen (Df Bz NCS) labeling method synthesis of melanin tumor PET imaging tracer [89Zr] Df Bz NCS Melan A antibody, simple synthetic method, productivity is higher, and about 54.75 ± 11.02%, radiochemicsl purity reaches more than 95%, stabilization in vitro, analyzes through TLC under 168h room temperature, has no the most de-zirconium performance.There is high sensitivity and specificity, be effectively improved PET CT effect in melanoma early diagnosis and curative effect monitoring, promote the life quality of melanoma patient.

Description

PET tracer of one species-specific diagnosis melanoma and preparation method thereof
Technical field
The invention belongs to the field of nuclear medicine, be specifically related to PET tracer and the system thereof of a species-specific diagnosis melanoma Preparation Method.
Background technology
Melanoma is the fastest-rising tumor of sickness rate in current all malignant tumor, by being positioned at epiderm skin basilar part Melanocyte cancerate and form, how to be developed by nevus or pigmented spots, once enter fast growing period, then poor prognosis, death Rate is high.90% melanoma betides skin, is most commonly in back, thorax abdomen and leg.American-European white race Crinis Carbonisatus in world wide Sick rate is apparently higher than other colour of skin ethnic group, and the melanoma sickness rate of European and American countries constantly rises.
Melan-A albumen is as the stronger mark of specificity, by the most private or be combined in diagnosis melanoma pathology Section statining.Melan-A is a kind of protein specific expressed at melanoma cell surface, and it is to be compiled by MLANA gene The albumen [14] of code, this protein fragments is made up of 9 aminoacid, and this protein can be by the MHC I in immune system T cell Complex identification, and then activated T lymphocytes, the high expressed of Melan-A is considered closely related with the transfer of melanoma [15].The most existing research is pointed out, in melanoma majority metastatic lesion, Melan-A albumen also has high expressed.Melan-A egg White expression is primarily targeted for cell membrane, for Melan-A albumen is provided theoretical foundation as the applied research of target site.
Positron emission tomography (Positron Emission Tomography, PET) is currently the only dissection Form mode carries out the nucleus medical image technology of function, metabolism and rii receptor, it can with hurtless measure ground, dynamically, quantitatively Observe medicine or metabolite enters the physiology in human body, Biochemical changes.PET is to utilize positron-emitting radionuclides and labelling thereof Compound is tracer, in function image mode, from molecular level display body and the metabolism of lesion tissue cell, function, blood Stream, cell proliferation and Rd distribution situation, provide the diagnostic message in terms of more physiology and pathology for clinic.PET shows More can objectively and accurately show the bio information of live body as result, in recent years, development is more rapid, at diagnosing tumor, by stages, again By stages and the aspect such as curative effect monitoring and Index for diagnosis has important clinical value.
" immune imaging PET (immune-PET) " monoclonal antibody radioactive label is at positron emission tomography (PET) In application, the real animal imaging according to specific targeted molecular becoming a kind of atraumatic, especially for body Interior primary tumo(u)r and the detection of metastatic lesion.For the isotope-labeled common coordination of antibody have zirconium 89 (89Zr, t1/2= 3.3d), iodine 124 (124I, t1/2=4.2d), copper 64 (64Cu, t1/2=12.7h), yttrium 89 (89Y, t1/2=3.3d).89Zr, half Phase of declining is basically identical with antibody drug, and its energy is situated between 18F and 68Ga, can obtain high-resolution PET imaging picture Etc. unique advantage [18], just becoming the popular isotope of immune-PET research nearly ten years.89Zr mark mode has a variety of, The mode that present stage is commonly used is Df-Bz-NCS chelating agen labeling method, and the method labelling productivity is high, and good stability is the shortest, skill Art is ripe, be applied to multiple antibody-89In Zr marker research.This research uses difunctional improvement chelating agen (Df-Bz-NCS) Labeling method synthesis of melanin tumor PET imaging tracer [89Zr]-Df-Bz-NCS-Melan-A polyclonal antibody, Simple synthetic method, productivity is higher, and about 54.75 ± 11.02%, radiochemicsl purity reaches more than 95%, and stabilization in vitro, under 168h room temperature Analyze through TLC, have no the most de-zirconium performance.
Melan-A is a kind of protein specific expressed at melanoma cell surface, and it is by MLANA gene code Albumen, this protein fragments is made up of 9 aminoacid, and this protein can be known by the MHC I complex in immune system T cell Not, and then activated T lymphocytes, the high expressed of melan-A is considered closely related with the transfer of melanoma.Because melan- The specificity that A albumen is expressed in melanoma cell, therefore is used for diagnosing melanin as staining pathologic section clinically Tumor.But, as it has been described above, pathological section can only diagnose the tissue of regional area, the overall condition of whole body can not be reflected, because of This, the melanoma PET diagnostic reagent developing a kind of novel identification melan-A albumen has the clinical practice valency of reality Value.
The means such as iconography means such as CT, MRI and PET-CT that currently mainly rely on assess the melanoma state of an illness, CT and MRI only provides morphology aspect information, has certain limitation.18F-FDG is higher to the recall rate of primary malignant melanoma, but Being to be 18.75% to lymphatic metastasis malignant melanoma focus early detective rate, this result explanation 18F-FDG is at melanin The effect played in the diagnosis of tumor metastasis is extremely limited.Thus the high specificity of melanoma PET-CT imaging urgently to be resolved hurrily point Sub-probe, had both improved sensitivity, had taken into account again specificity.
Summary of the invention
Goal of the invention: it is an object of the invention to provide one and both improved sensitivity, take into account again specific specific diagnosis PET tracer of melanoma and preparation method thereof.
Technical scheme:
The preparation method of the PET tracer of specific diagnosis melanoma, including following several steps:
1) melan-A antibody solvent displacement: use sodium bicarbonate solution displacement method, by 1.5mg melan-A antibody lyophilizing Powder is dissolved in solvent, and centrifugal concentrating；
2) melan-A antibody-Df-Bz-NCS-modify: take step 1) replacement solvent and concentration after melan-A antibody Solution, regulation pH value is 7.0, add 20mg/mL DFO with DMSO as solvent (DFO, one can with various metals from The chelating agen that son combines) solution, reacts 1h in 36 DEG C of oil baths, every 10min abundant oscillating reactions pipe, obtains-Df-Bz- The melan-A antibody that NCS-modifies；
3) purification of melan-A antibody that-Df-Bz-NCS-modifies: by step 2)-the Df-Bz-NCS-that obtains modifies Melan-A antibody passes through PD10 post and 0.15mol/L (PH=7.2) sodium acetate buffer purification；
4)[89Zr] synthesis of-Df-Bz-NCS-Melan-A antibody: taking radioactivity is 3mCi's89Zr oxalic acid solution 0.5ml, adds the sodium carbonate liquor of 0.1mol/L, and regulation pH value is 7.0, adds the 0.15mol/L (PH=7.2) of 0.3ml Sodium acetate buffer, in aforementioned system, then add step 3) melan-A that the modifies of-Df-Bz-NCS-that obtains resists Body, reacts 40min under room temperature；
5)[89Zr] purification of-Df-Bz-NCS-Melan-A antibody: by step 4) gained [89Zr]-Df-Bz-NCS- Melan-A antibody passes through PD10 post and 0.15mol/L (PH=7.2) sodium acetate buffer purification, i.e. obtain [89Zr]-Df- The Bz-NCS-Melan-A antibody i.e. PET tracer of specific diagnosis melanoma.
The present invention passes through radioactivity paper chromatography (RTLC) detection of radioactive chemical purity, by radioactivity paper chromatography (RTLC) Detection product stability in room temperature places 168h.
Beneficial effect: the present invention uses difunctional improvement chelating agen (Df-Bz-NCS) labeling method synthesis of melanin tumor PET Imaging tracer [89Zr]-Df-Bz-NCS-Melan-A antibody, simple synthetic method, productivity is higher, and about 54.75 ± 11.02%, Radiochemicsl purity reaches more than 95%, stabilization in vitro, analyzes through TLC under 168h room temperature, has no the most de-zirconium performance.There is high sensitivity And specificity, it is effectively improved PET-CT effect in melanoma early diagnosis and curative effect monitoring, promotes melanomatosis The life quality of people.
Accompanying drawing explanation
Fig. 1 be the present invention [89Zr] the building-up process schematic diagram of-Df-Bz-NCS-Melan-A antibody.
Fig. 2 is the cell line Melan-A protein expression western blot qualification figure of Application Example of the present invention.
Fig. 3 is the melan-A overexpression cell line mice with tumor microPET scanning figure of Application Example of the present invention.
Detailed description of the invention
Embodiment 1
As it is shown in figure 1, the preparation method of the PET tracer of specific diagnosis melanoma, including following several steps:
1) melan-A antibody solvent displacement: by molten for 1.5mg Melan-Apolyclonal antibody freeze-dried powder preparation In 1ml 0.1mol/L sodium bicarbonate solution, take one, PD10 post, after cleaning with ultra-pure water, add 0.1mol/L sodium bicarbonate molten Liquid balances, and after balance is good, takes 1mL melan-A antibody stock solution and adds PD10 post stigma end, add appropriate sodium bicarbonate solution, After dried liquid stream in post, discard all effluent, continuously add 3mL 0.1mol/L sodium bicarbonate solution, collect all liquid Body.Take ultra-filtration centrifuge tube one, liquid centrifugal (1500rpm × 5min) will be collected, concentrate；
2) melan-A antibody-Df-Bz-NCS-modify: take step 1) replacement solvent and concentration after melan-A antibody Solution, regulation pH value is 7.0, adds the DFO solution with DMSO as solvent of 20mg/mL, reacts 1h in 36 DEG C of oil baths, every 10min abundant oscillating reactions pipe, obtains the melan-A antibody that-Df-Bz-NCS-modifies；
3) purification of melan-A antibody that-Df-Bz-NCS-modifies: by step 2)-the Df-Bz-NCS-that obtains modifies Melan-A antibody passes through PD10 post and 0.15mol/L (PH=7.2) sodium acetate buffer purification, takes one, PD10 post, with super After pure water cleans, add the sodium acetate buffer balance of 0.15mol/L (PH=7.2).Balance adds above-mentioned reaction after terminating Crude product, adds hac buffer, after dried liquid stream in post, discards all effluent.Continuously add 3mL acetate buffer molten Liquid, collects all liq.Take ultra-filtration centrifuge tube one, liquid centrifugal (1500rpm × 5min) will be collected, concentrate and delay with acetic acid Dissolved liquid washs for several times；
4)[89Zr] synthesis of-Df-Bz-NCS-Melan-A antibody: taking radioactivity is 3mCi's89Zr oxalic acid solution 0.5ml, adds the sodium carbonate liquor of 0.1mol/L, and regulation pH value is 7.0, adds the 0.15mol/L (PH=7.2) of 0.3ml Sodium acetate buffer, in aforementioned system, then add step 3) melan-A that the modifies of-Df-Bz-NCS-that obtains resists Body, reacts 40min under room temperature；
5)[89Zr] purification of-Df-Bz-NCS-Melan-A antibody: by step 4) gained [89Zr]-Df-Bz-NCS- Melan-A antibody passes through PD10 post and 0.15mol/L (PH=7.2) sodium acetate buffer purification, i.e. obtain [89Zr]-Df- The Bz-NCS-Melan-A antibody i.e. PET tracer of specific diagnosis melanoma.
The product obtaining embodiment 1 carries out purity and Detection of Stability:
1. by radioactivity paper chromatography (RTLC) detection of radioactive chemical purity.
ITLC method measures radio-chemical purity: draws and obtains in the marked product of 10 μ l89Zr-Df-Bz-NCS- Melan-A antibody-solutions, with iTLC glass fibre for fixing phase (1cm x 8cm instant silica gel strip), so After with concentration as 20mmol/L, pH value be 6.5 citric acid-sodium citrate be that developing solvent launches, be dried, according to Chinese Pharmacopoeia Two annex XIII radiochemical purity algoscopy the first methods of version in 2010, measure its radio-chemical purity；Its result Without free89Zr ion.
2. detect product stability in room temperature places 168h, operational approach by radioactivity paper chromatography (RTLC)
Fetch and deliver medicine to keep sample medicine, carry out iTLC analysis according to time point 1h, 2h, 6h, 24h, 48h, 72h, 120h and 168h. The Rf value of each time point is respectively as follows: 0.185,0.179,0.163,0.168,0.169,0.169,0.163 and 0.168, not Find significantly89Zr ion is unimodal.
89After Zr oxalic acid solution and Df-Bz-NCS-Melan-A antibody response, unconjugated in solution89Zr oxalic acid solution (Rf=0.5),89Zr-Df-Bz-NCS-Melan-A antibody products close to source point (Rf=0.1), illustrates without free89Zr, Radio-chemical purity > 99%.The marked product obtained in the present invention is stored at room temperature in 168h, its radio-chemical purity > 99%, good stability.
Application Example
Small animal position emission tomography (PET) scanning and bio distribution:
SK-MEL-28 and A375 total protein of cell Melan-A expresses western blot checking
The A375 of Humanized cell strain SK-MEL-28 and the melan-A feminine gender filtering out expression positive for melan-A is thin Born of the same parents, cultivate amplification at cell culture incubator, and dystopy is inoculated in nude mice oxter, use two kinds of cells of western blot experimental identification The expression of melan-A.As shown in Figure 2, SK-MEL-28 cell line Melan-A expresses the positive, high expressed Melan-A；A375 Cell line Melan-A expresses feminine gender, low expression Melan-A
89Zr-Df-Bz-NCS-Melan-A antibody is microPET imaging in lotus tumor BALB/c nude mouse:
The injection of SK-MEL-28 mice with tumor [89Zr] 2h after-DFO-Df-Bz-Melan-A antibody, 6h, 24h, 72h, 120h and 168h images as shown in Figure 3.ROI semi-quantitative analysis shows, SK-MEL-28 mice with tumor tumor locus for developer absorb in Reach maximum after 72h, uptake values about 15.85 ± 2.56%ID/g.
Thus embodiment understands, and 89Zr-Df-Bz-NCS-Melan-A antibody prepared by the present embodiment has preparation method Simply, productivity is high, radiochemicsl purity is high, stabilization in vitro is good, specificity advantages of higher, in reaction live body that can be objective and accurate in tumor The expression of Melan-A, can diagnosis melanoma more in early days.Additionally animal uses identical PET tracer with human body, Melan-A albumen expresses high conservative at different genera, and 89Zr-Df-Bz-NCS-Melan-A antibody prepared by the present embodiment can It is widely used in clinical stage melanoma PET diagnosis and tumor efficiency is assessed, and provide for melanoma transfer diagnosis in early days Imaging evidence reliably.

Claims (2)

1. the PET tracer of a species-specific diagnosis melanoma, it is characterised in that this tracer is89Zr labelling melan-A resists The marked product of body.
The preparation method of the PET tracer of specific diagnosis melanoma the most according to claim 1, it is characterised in that Including following several steps:
1) melan-A antibody solvent displacement: use sodium bicarbonate solution displacement method, by 1.5mg melan-A antibody freeze dried powder It is dissolved in solvent, and centrifugal concentrating；
2) melan-A antibody-Df-Bz-NCS-modify: take step 1) replacement solvent and concentration after melan-A antibody-solutions, Regulation pH value is 7.0, adds the DFO solution with DMSO as solvent of 20mg/mL, reacts 1h, every 10min in 36 DEG C of oil baths Fully oscillating reactions pipe, obtains the melan-A antibody that-Df-Bz-NCS-modifies；
3) purification of melan-A antibody that-Df-Bz-NCS-modifies: by step 2)-the Df-Bz-NCS-that obtains modifies Melan-A antibody passes through PD10 post and 0.15mol/L (PH=7.2) sodium acetate buffer purification；
4)[89Zr] synthesis of-Df-Bz-NCS-Melan-A antibody: taking radioactivity is 3mCi's89Zr oxalic acid solution 0.5ml, Adding the sodium carbonate liquor of 0.1mol/L, regulation pH value is 7.0, adds the acetic acid of the 0.15mol/L (PH=7.2) of 0.3ml Sodium buffer solution, then adds step 3 in aforementioned system) the melan-A antibody the modified of-Df-Bz-NCS-that obtains, room temperature Lower reaction 40min；
5) purification of [89Zr]-Df-Bz-NCS-Melan-A antibody: by step 4) [89Zr]-Df-Bz-NCS-of gained Melan-A antibody passes through PD10 post and 0.15mol/L (PH=7.2) sodium acetate buffer purification, i.e. obtains [89Zr]-Df- The Bz-NCS-Melan-A antibody i.e. PET tracer of specific diagnosis melanoma.
CN201610539882.8A 2016-07-08 2016-07-08 PET tracer of one species-specific diagnosis melanoma and preparation method thereof Pending CN106110343A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610539882.8A CN106110343A (en) 2016-07-08 2016-07-08 PET tracer of one species-specific diagnosis melanoma and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610539882.8A CN106110343A (en) 2016-07-08 2016-07-08 PET tracer of one species-specific diagnosis melanoma and preparation method thereof

Publications (1)

Publication Number Publication Date
CN106110343A true CN106110343A (en) 2016-11-16

Family

ID=57282824

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610539882.8A Pending CN106110343A (en) 2016-07-08 2016-07-08 PET tracer of one species-specific diagnosis melanoma and preparation method thereof

Country Status (1)

Country Link
CN (1) CN106110343A (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060057062A1 (en) * 2004-09-10 2006-03-16 Trotter Dinko G Compositions and methods useful in pretargeted imaging
CN104645364A (en) * 2015-01-27 2015-05-27 南京江原安迪科正电子研究发展有限公司 Mark product of <89>Zr marked denosumab, and preparation method and application thereof
CN104725510A (en) * 2015-01-27 2015-06-24 米度（南京）生物技术有限公司 Labelling product for labelling Ipilimumab by 89Zr and preparation method thereof, and quality control method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060057062A1 (en) * 2004-09-10 2006-03-16 Trotter Dinko G Compositions and methods useful in pretargeted imaging
CN104645364A (en) * 2015-01-27 2015-05-27 南京江原安迪科正电子研究发展有限公司 Mark product of <89>Zr marked denosumab, and preparation method and application thereof
CN104725510A (en) * 2015-01-27 2015-06-24 米度（南京）生物技术有限公司 Labelling product for labelling Ipilimumab by 89Zr and preparation method thereof, and quality control method

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王伯沄 等: "《病理学技术》", 31 March 2001, 人民卫生出版社 *

Similar Documents

Publication Publication Date Title
Börjesson et al. Performance of immuno–positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients
Yao et al. Infection imaging with 18F-FDS and first-in-human evaluation
CN108434468B (en) Radioiodinated protein binding ligand and application thereof
CN102781316A (en) Cancer diagnosis and imaging
Haubner et al. [68 Ga] NODAGA-RGD–Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis
Garai et al. Limitations and pitfalls of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) scintigraphy
CN103830753A (en) Imaging drug &lt;68&gt;Ga-NOTA-IF7 targeting Anxa1 in tumor blood vessels and preparation method thereof
CN106581700A (en) Novel HER2-targeting polypeptide radioactive medicine and preparation method and application thereof
CN105126128A (en) Novel tumor VEGFR-3 molecular photographic developer and application thereof
CN110305187A (en) Prostate cancer PET diagnostic reagent68Ga-NOTA-ANCP-PSMA and its preparation method and application
CN113583089A (en) PET imaging agent targeting tumor PD-L1, labeled precursor thereof, preparation method and application
CN103833829A (en) Radioactive &lt;18&gt;F-labeled imaging drug &lt;18&gt;F-AL-NOTA-IF7 targeting Anxa1 in tumor blood vessels and preparation method thereof
CN106474495B (en) Imido- oxalic acid99mThe rgd peptide cancer diagnosis drug and preparation method thereof of Tc label
CN103030689B (en) CART polypeptide compound, and preparation method and application of compound
Zhao et al. Radiosynthesis and Preliminary Biological Evaluation of 18 F-Fluoropropionyl-Chlorotoxin as a Potential PET Tracer for Glioma Imaging
US20230105190A1 (en) Fapi dimer compound, fapi dimer-based positron emission tomography (pet) imaging agent for tumor diagnosis, and preparation method and use thereof
CN105524610B (en) Multi-modal leucocyte molecular probe compound, preparation method and application
CN108434469A (en) A kind of HER2 affinities body68Ga markers and preparation method thereof, application
CN106110343A (en) PET tracer of one species-specific diagnosis melanoma and preparation method thereof
US20200078478A1 (en) Structural molecule of peptide derivative for PSMA-targeting radiotherapy diagnosis and treatment
CN110305186A (en) Prostate cancer PET diagnostic reagent68Ga-DOTA-ANCP-PSMA and its preparation method and application
Traub-Weidinger et al. Preliminary experience with 68Ga-DOTA-lanreotide positron emission tomography
CN102617728B (en) Preparation process of 18F labeled product of Exendin-4
CN104645362A (en) Preparation process of positron imaging agent 18F-5-floro-N-(2-(diethylamino) ethyl) pyridinecarboxamide
Wang et al. Radiation dosimetry estimates of 18F-alfatide II based on whole-body PET imaging of mice

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20161116

RJ01 Rejection of invention patent application after publication