PANICHELLI PAOLA (IT)
MARTINI DOMENICO (IT)
VALENTINI GIANLUCA (IT)
PANICHELLI PAOLA (IT)
MARTINI DOMENICO (IT)
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SZAJEK, L. P. ET AL: "Semi-remote production of [64Cu]CuCl2 and preparation of high specific activity [64Cu]Cu-ATSM for PET studies", XP002436404, retrieved from STN Database accession no. 143:412232
| CLAIMS
1. Chemical synthesis Of 64 CUASP (Copper64-Asparagine) characterized by
the combination of the Copper 64 isotope with Asparagine according to the
formula 64 Cu(ASp) 2 for PET investigations or for radiotherapy investigations.
2. Chemical synthesis of 64 CUASP (Copper64- Asparagine) as claimed in
claim 1 characterized by the formula 64 Cu(Asp) 2 2H 2 O.
3. Chemical synthesis of 64 CUASP (Copper64-Asparagine) as claimed in
claims 1 and 2 characterized by the formula [ 64 Cu(ASn)(OH)(H 2 O) 2 ].
4. Chemical synthesis of 64 CUASP (Copper64-Asparagine) as claimed in
claims 1, 2, 3 characterized by the formula [ 64 Cu(ASn)(H 2 O) 4 ] (I).
5. Chemical synthesis of 64 CUASP (Copper64- Asparagine) as claimed in
claims 1, 2, 3, 4 characterized by the coordination of asparagine to the metal
with a reaction between acceptor Cu and Asparagine.
6. Chemical synthesis of 64 CUASP (Copper64-Asparagine) as claimed in
claims 1, 2, 3, 4, 5 characterized in that it can be administered by general
parenteral route in the form of aqueous or oily solutions or in suspension in
suitable dispersing agents even in the form of freeze-dried products to be
dispersed at the time of administration.
7. Chemical synthesis of 64 CUASP (Copper64- Asparagine) as claimed in
claim 6 characterized in that it can be administered by general oral route in
the form of tablets, oily or percolate soft or hard gelatin capsules, sugarcoated
pills, dispersible powders, suspensions or emulsions.
8. Chemical synthesis of 64 CUASP (Copper64-Asparagine) as claimed in
claim 6 characterized in that it can be administered by topical or transdermal
route in suitable forms and in vehicles or devices suitable for administration
of the active ingredient at the primary and/or secondary site of the tumour.
9. Chemical synthesis of 64 CUASP (Copper64-Asparagine) as claimed in the
previous claims and as described and illustrated for the specified objects. |
Title: "Chemical synthesis of 64 CUASP (Copper64-Asparagine) for PET
investigations and for radiotherapy".
The present invention concerns a new molecule, 64-copper(II)asparagine, that
in the PET diagnostic method allows a double use in "vivo": a diagnostic use
and a radiotherapeutic use.
PET (Position Emission Tomography) is a method that enables the study of
the metabolism of the various organs examined, so allowing early diagnostic
parameters of various pathologies to be obtained. In recent years, the use of
this method has spread considerably in the USA, and the number of PET
diagnostic centres is currently increasing throughout Europe, mainly in the
oncological sector. In this sector, PET introduces two clinical parameters,
namely early diagnosis and therapy optimisation, that change the life
expectancy of patients and improve the management of their disease.
Other fields of application, such the neurological, cardiological and
rheumatological fields, are playing an increasingly greater role. In an age
where there is a continual increase in the average length of life, PET will
certainly play an important role in the study of age-related diseases, such as
Parkinson's and Alzheimer's, as well as in the study of molecules with which
it is possible to make an early diagnosis of the onset of acute cardiac events
that today are one of the main causes of death.
PET is carried out by injecting patients with a radiopharmaceutical and
following the distribution of the radiopharmaceutical inside the body with
specific machines called PET Tomographs.
Radiopharmaceuticals consist of two main parts, one of which is the
radioisotope (which emits beta radiations) and the other a molecule that will
bind to the radioisotope and is the metabolic substrate of the PET
investigation. Radioisotopes are produced by an instrument called a cyclotron
and are bound to the molecule that one wishes to study through specific
chemical synthesis methods.
The most commonly used radioisotope today is 18-Fluorine that has a half-
life of about two hours and has suitable chemical characteristics to make it
easily bound, in liquid form, to various molecules.
The most commonly used molecule today is 18-Fluoro-deoxy glucose (FDG)
that enables identification of the sites inside the body that have a greater
glucose consumption than the normal metabolic standards and that may
therefore be of a cancerous nature.
The emerging limit of this application is its insufficient specificity in
distinguishing tumour sites from sites of infection. In this regard, other
molecules, such as Fluoro-choline or Fluoro-thymidine, have been tested;
these molecules increase diagnostic specificity especially in some tumoral
forms such as prostate tumour or pulmonary and cerebral tumour.
Another sector in which PET diagnostics is developing rapidly is in the
development of radiotherapy treatment plans that allow optimisation of the
therapeutic effect. In this regard, there are various research development
stages in the sector that range from a demonstrated usefulness of FDG to the
recent experiments with the 64-Cu-ATSM molecule that allows a map of
oxygen distribution within the tumoral mass to be obtained. This molecule is
synthesised in the USA and modifies treatment plans in the sense of its ability
to reduce the intervention area and the exclusion of areas that do not show
oxygen and therefore do not offer radiotherapy response possibilities.
Experiments of this type also exist with molecules marked with 18-Fluorine,
such as F-MISO, but the half-life characteristics of 64-Copper, about 12
hours, make it today a radioisotope of great interest for the prospects of the
sector.
The present invention concerns the testing and the synthesis of the Copper-64
radioisotope with the Asparagine molecule that leads to the production of a
new molecule, Copper-64-Asparagine, whose abovementioned components
give it a double potential in "vivo": for diagnostic treatment and for
radiotherapeutic treatment, which today is not possible with the molecules
known until now.
Therefore, the subject of the present invention are copper complexes of
general formula 64 Cu(Asp) 2 ; 64 Cu(Asp) 2 2H 2 O; [ 64 Cu(ASn)(OH)(H 2 O) 2 ];
[ 64 Cu(ASn)(H 2 O) 4 ] (I), whose molecular structures are shown in the following
drawings:
- figure 1 shows the molecular structure of the general formula
64 Cu(ASp) 2 2H 2 O
- figure 2 shows the molecular structure of the general formula
[ 64 Cu(ASn)(OH)(H 2 O) 2 ]
- figure 3 shows the molecular structure of the general formula
[ 64 Cu(ASn)(H 2 O) 4 ] (I)
- figure 4 shows the molecular structure of the general formula 64Cu(Asp) 2
where R 1 = O or NH 2 ; R 2 = CONH 2 or CH 2 COOH.
Synthesis takes place by taking 10 mCi Of 64 CuCl 2 , drying it and adding 100
μl of a 6 10 "2 mol/1 solution of L-Asparagine (or D-Asparagine or DL-
Asparagine) in pH 5.5 acetate buffer. The solution is passed through a 0.22
μm filter and is diluted with saline solution. Another synthesis route involves
drying 10 mCi of 64 CuCl 2 and adding 100 μl of a 6 10 "2 mol/1 solution of L-
Asparagine (or D-Asparagine or DL-Asparagine) in a solution containing
ammonium sulphate, potassium monoacid phosphate, potassium diacid
phosphate, sodium citrate and magnesium sulphate at pH 7. The solution is
passed through a 0.22 μm filter and is diluted with saline solution.
Next Patent: SELECTING AUTOFOCUS AREA IN AN IMAGE