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Home » RADIOLABELLED » FDA approves second brain imaging drug Vizamyl (flutemetamol F 18 injection)to help evaluate patients for Alzheimer’s disease, dementia

FDA approves second brain imaging drug Vizamyl (flutemetamol F 18 injection)to help evaluate patients for Alzheimer’s disease, dementia

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  is the structure on right

Vizamyl (flutemetamol F 18 injection)

http://jnm.snmjournals.org/content/50/8/1251/F1.expansion.html get structure

 

Chemical name: 2-{3-[18F]fluoro-4-(methylamino)phenyl}-1,3-benzothiazol-6-ol    diagnostic aid
Cas Number 765922-62-1
INN  name flutemetamol
Molecular Formula:

GE Healthcare

FDA PRESS RELEASE

For Immediate Release: Oct. 25, 2013

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm372261.htm

The U.S. Food and Drug Administration today approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug for use with positron emission tomography (PET) imaging of the brain in adults being evaluated for Alzheimer’s disease (AD) and dementia.

Dementia is associated with diminishing brain functions such as memory, judgment, language and complex motor skills. The dementia caused by AD is associated with the accumulation in the brain of an abnormal protein called beta amyloid and damage or death of brain cells. However, beta amyloid can also be found in the brain of patients with other dementias and in elderly people without neurologic disease.

Vizamyl works by attaching to beta amyloid and producing a PET image of the brain that is used to evaluate the presence of beta amyloid. A negative Vizamyl scan means that there is little or no beta amyloid accumulation in the brain and the cause of the dementia is probably not due to AD. A positive scan means that there is probably a moderate or greater amount of amyloid in the brain, but it does not establish a diagnosis of AD or other dementia. Vizamyl does not replace other diagnostic tests used in the evaluation of AD and dementia.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm372261.htm

About GE Healthcare

GE Healthcare provides transformational medical technologies and services to meet the demand for increased access, enhanced quality and more affordable healthcare around the world. GE GE -0.23% works on things that matter – great people and technologies taking on tough challenges. From medical imaging, software & IT, patient monitoring and diagnostics to drug discovery, biopharmaceutical manufacturing technologies and performance improvement solutions, GE Healthcare helps medical professionals deliver great healthcare to their patients.

For our latest news, please visit http://newsroom.gehealthcare.com

Flutemetamol [ 18 F] Injection is a diagnostic positron emission tomography (PET) agent for the imaging of β-amyloid plaques in the brain. The synthesis of the agent can be performed using automated synthesis platforms with or without using specially-tailored cassettes. For example, the synthesis can be performed using either the TRACERlab FX F-N platform or the FASTlab™ platform, commercially available from GE Healthcare a division of General Electric Company in conjunction with auxiliary preparative high pressure liquid

chromatography equipment. After synthesis, the bulk agent is transferred to high pressure liquid chromatography (HPLC) equipment to separate the physico-chemically similar compounds [ 18 F] flutemetamol from its deprotected precursor, AHl 11832 (6-hydroxy-2-(4′-(N- methyl)amino-3′-nitro)phenylbenzothiazole) and hence obtain purified [ 18 F] flutemetamol.

However there still exists a need in the art for alternative purification methods for the preparation of [ 18 F] flutemetamol. The invention as described below answers such a need. Specifically, Applicants have now found a process that eliminates the use of preparative HPLC equipment. SUMMARY OF THE INVENTION

As [ 18 F]flutemetamol and its deprotected precursor, AH111832 (6-hydroxy-2-(4′-(N- methyl)amino-3′-nitro)phenylbenzothiazole) are physico-chemically very similar, preparative HPLC is required to separate them. However, Applicants have now found that it is possible to replace the preparative HPLC equipment in previous purification processes with low cost, single-use solid phase extraction (SPE) cartridges for purification of [ 18 F]flutemetamol.

Accordingly, the present invention provides a purification process comprising the following steps:

(a) passing a diluted crude product reaction mixture comprising flutemetamol through a first reverse phase SPE cartridge;

(b) washing said first reverse phase SPE cartridge with a water/acetonitrile,

tetrahydrofuran(THF)/water, methanol(MeOH)/water or isopropanol/water mixture; preferably, a water/acetonitrile mixture;

(c) rinsing said first reverse phase SPE cartridge with water once step (b) is completed; (d) eluting said first reverse phase SPE cartridge with acetonitrile or tetrahydrofuran; preferably, acetonitrile;

(e) directly passing the mixture from said eluting step (d) through a normal phase SPE cartridge to give an acetonitrile or tetrahydrofuran solution; preferably, an acetonitrile solution, comprising purified flutemetamol; (f) diluting said acetonitrile or tetrahydrofuran solution; preferably, an acetonitrile solution, comprising purified flutemetamol, with water to form a diluted water/acetonitrile or a diluted water/tetrahydrofuran solution; preferably, a diluted water/acetonitrile solution, comprising purified flutemetamol, wherein said water/acetonitrile solution contains about 40- 70% (v/v) water; preferably at least about 40% (v/v) water; more preferably at least about 50% (v/v) water;

(g) passing the diluted water/acetonitrile or diluted water/tetrahydrofuran solution; preferably, diluted water/acetonitrile solution, comprising purified flutemetamol of step (f) through a second reverse phase SPE cartridge and trapping the flutemetamol on said cartridge second reverse phase SPE cartridge;

(h) rinsing said second reverse phase SPE cartridge with water; and

(i) eluting the trapped purified flutemetamol from second reverse phase SPE cartridge with an injectable organic solvent; preferably, ethanol or DMSO; preferably with ethanol.

According to the invention, the purified flutemetamol can be collected after step (i).

The present invention also provides a purification process of the present invention, wherein the process is automated.

 

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Alzheimer’s disease (AD) is defined histologically by the presence of extracellular β-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. The diagnosis of dementia, along with the prediction of who will develop dementia, has been assisted by magnetic resonance imaging and positron emission tomography (PET) by using [18F]fluorodeoxyglucose (FDG). These techniques, however, are not specific for AD. Based on the chemistry of histologic staining dyes, several Aβ-specific positron-emitting radiotracers have been developed to image neuropathology of AD. Among these, [11C]PiB is the most studied Aβ-binding PET radiopharmaceutical in the world. The histologic and biochemical specificity of PiB binding across different regions of the AD brain was demonstrated by showing a direct correlation between Aβ-containing amyloid plaques and in vivo [11C]PiB retention measured by PET imaging. Because 11C is not ideal for commercialization, several 18F-labeled tracers have been developed. At this time, [18F]3′-F-PiB (Flutemetamol), 18F-AV-45 (Florbetapir), and 18F-AV-1 (Florbetaben) are undergoing extensive phase II and III clinical trials. This article provides a brief review of the amyloid biology and chemistry of Aβ-specific 11C and 18F-PET radiopharmaceuticals. Clinical trials have clearly documented that PET radiopharmaceuticals capable of assessing Aβ content in vivo in the brains of AD subjects and subjects with mild cognitive impairment will be important as diagnostic agents to detect in vivo amyloid brain pathology. In addition, PET amyloid imaging will also help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of antiamyloid therapeutics currently under development in clinical trials.

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DR ANTHONY CRASTO

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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