[0001] The present invention relates generally to a method for labeling with Radiotracer Synthesizer, wherein the system Developed a radioactive tracer for cancer detection and treatment in Easy, convenient and User friendly way with wide range of tracer molecule, wherein the produced radioactive tracer is cost and time efficient.
BACKGROUND OF THE INVENTION
[0002] cancer is a most frequent and the leading cause of cancer death in worldwide. One of the key issues in treatment of this cancer is the detection of recurrent disease or metastases. In view of the fact that cancer cells tend to spread to other organs such as the bones and lymph nodes, early detection of the cancer tumor is highly desirable to prevent metastases formation, and furthermore, effective treatment strategies for cancer metastases are urgently needed.

[0003] Recently, some very interesting clinical results based on gallium-68 radiolabeled molecules for imaging in vivo by PET were published and presented. These radiotracers are generally made by assembly of a chelating agent with a targeting agent, generally DOTA-functionalized targeting agents, allowing, respectively, the reaction with a metallic radioisotope or radiometal and biological/metabolic activity of the radiotracer. However, due to the short half-life of gallium-68 (68 minutes), the radiotracer, i.e. radiolabeled chelate-functionalized targeting agent, based on this radioisotope are not suitable for long-distance distribution and require on the spot production and suitable production equipment, such as synthesizers, for the radiolabelling process, making it difficult for widespread use in routine nuclear medicine.
[0004] Gallium-68 itself is obtained from a generator. Said generator is an alternative to the in situ production using a cyclotron or daily delivery of radioisotopes. The system was initially developed for technecium-99m. The principle is based on the radiochemical separation between a parent element of long half-life (or nonradioactive elements such as germanium-68) contained in the generator and a daughter element which is a short half-life element resulting from the disintegration of the parent element. The daughter is recovered with excellent radiochemical purity and radionuclidic properties (i.e. without contamination from other radionuclides or other radiochemical impurities) and with good chemical purity (low metal ion content). This separation is made possible by the different chemical properties of the two elements (parent and daughter).

[0005] Currently, DOTA is the mostly used chelator for the complexation of radio-metals such as 68Ga, 177Lu and 90Y, for both diagnostic and therapeutic application. However, labeling reactions using DOTA as the chelating agent are usually carried out at high temperatures under acidic conditions and require long reaction times, which might result in decomposition of the PSMA ligand, the radioactive isotope, or both.
[0006] In the state of the art, the presence of metal ions that compete with gallium-68 is generally reduced by pre-labelling purification or fractionation. These additional steps however represent a loss of radioactivity resulting from, either wasted time or the process itself. These losses can reach up to 30% of the total radioactivity, respectively, 10% due to decay and 20% coming from the pre-purification process itself.
[0007] In addition, the need for these pre- and post-labelling purification steps makes these gallium-68 labeled radiotracer synthesis dependent, to some extent, on automation and on the use of a synthesis module. In addition to technical expertise, this requires extra time loss unfavorable to the overall performance.
[0008] In this context, it is clear that a need exists for an improved process for the preparation of 68Ga complex which overcomes one or more of the above mentioned problems. This involves identifying an appropriate medium that maintains the pH within a tolerable range, to handle the metal contamination,

which avoids the need to heat for promoting the chelating reaction and allows gallium-68 chelation higher yields .
[0009] All of the prior art stated methods and devices/systems or protocol and some other methods and devices/systems or protocol presently known in the art have had some flaws in design or mechanism and lacks precision. Most of the existing protocol are not very secure and time consuming when transfer repetitive of similar data requests from the original. Some shortfalls of the existing methods and systems and protocols include time, cost and purity. In light of this, there is a need for a method and system and protocol that overcomes these constraints.
[00010] Despite the aforesaid drawbacks, there exists a need to provide a method that produces Very fast labeling with predefined labeling protocols for fully reproducibility, wherein Synthesis time 10 minutes only with an efficiency of 100 percent and with Radiochemical purity more than 95 %.
[00011] The present invention addresses the issues as discussed above.

SUMMARY OF THE PRESENT INVENTION
[00012] An object of the present invention is to provide a method for generating Radioactive tracer for cancer detection in Easy, convenient and User friendly way with wide range of tracer molecule, wherein Synthesis time is 10 minutes only with an Efficiency of 100 % and Radiochemical purity more than 95 %.
[00013] It has now been found, in accordance with the present invention, that highly-efficient radiolabeling with the radioactive isotope 68Ga, can be carried out in a fast, simple and safe manner which renders the use of the current synthesis module, and the requirements for the whole protecting constructions associated therewith, redundant. As shown herein, such a process is applicable for radioactive isotopes other than 68Ga as well.
[00014] Another object of the present invention to provide method or system that generate Radiotracer in a Time and money saving manner.
[00015] Another object of the present invention to provide a system that is very compact in size.
[00016] Another object of the present invention to provide method or system that generate Radiotracer with Great Performance.
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[00017] Another object of the present invention to provide method or system that is Easy and convenient, User friendly and Synthesizing wide range of radio tracer.
[00018] Another object of the present invention to provide system that improve production of a Radiotracer and a corresponding improved method.
[00019] Another object of the present invention to provide system that generate more stable tracers than known from the prior art.
[00020] Another object of the present invention to provide system, wherein a gallium 68 is generate when HCL is passed through gallium generator.
[00021] In order to maintain the pH of the gallium 68, a buffering medium is used, wherein the buffer must be nontoxic, must effectively maintain the pH within a range of 3.0 to 5.0, should not compete with gallium-68 ions. it must be strong enough to maintain the pH within the desired range with 10% changes in the generated gallium 68 from gallium generator.
[00022] The details of one or more implementations are set forth in the accompanying description below. Other aspects, features and advantages of the subject matter disclosed herein will be apparent from the description and the claims.
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DETAILED DESCRIPTION OF THE INVENTION:
[00023] As required, an exemplary-only embodiment of the present application is disclosed herein; however, it is to be understood that the disclosed embodiment is merely exemplary of the present disclosure, which may be embodied in various and / or alternative forms. Specific process details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed processes.
[00024] Aspects, advantages and/or other features of the exemplary embodiment of the disclosure will become apparent in view of the following detailed description, which discloses various non-limiting embodiments of the invention. In describing exemplary embodiments, specific terminology is employed for the sake of clarity. However, the embodiments are not intended to be limited to this specific terminology. It is to be understood that each specific portion includes all technical equivalents that operate in a similar manner to accomplish a similar purpose.
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[00025] Exemplary embodiments may be adapted for many different purposes and are not intended to be limited to the specific exemplary purposes set forth herein. Those skilled in the art would be able to adapt the exemplary-only embodiment of the present disclosure, depending for example, on the intended use of adapted embodiment. Moreover, examples and limitations related therewith brought herein below are intended to be illustrative and not exclusive. Other limitations of the related art will become apparent to those of skill in the art upon a reading of the following specification and a study of the related figures. The invention will be more clearly understood from the following description of the product thereof.
[00026] The present invention describes new methods for radiolabeling with suitable radioactive isotopes, such as 68Ga under mild reaction conditions (e.g., room temperature) and for short periods of time (e.g., 3 to 30 minutes), , wherein said radiolabeled radiotracer is suitable for the diagnosis or therapy of cancer. Accordingly, the present invention provides methods for radiolabeling, which are both simple and fast, and require neither sophisticated nor expensive equipment as required by the automated synthesis module currently available, such as the "hot-cell".
[00027] Moreover, since the method of the invention enables over 95% binding of the radiotracer, it eliminates the need for a step of removing unbound tracer from the reaction vial, which is an essential step of the presently known labeling methods.
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[00028] A 68 Ge / 68 Ga-generator provides the required 68 for marking gallium. The 68 Ge / 68 Ga-generator is react with hydrochloric acid, for example, the concentration is 0.1 mol / l. In this way, 68 gallium is generated.
[00029] 68 Gallium is called by means of so-called gallium-68 generators, also 68 Ge / 68 Ga generators, generated from 68 germanium.
[00030] The invention also encompasses the 68 gallium obtained by passing HCL in a gallium-68 generator.
[00031] The generated 68 gallium is collected in a reactor, wherein the reactor comprises a precursor and a buffer, mix the collected 68 gallium with the precursor and the buffer and heat the mixture at room temperature, wherein the buffer and precursor is used in order to maintain the PH value.
[00032] In an embodiment the mixture may be heated to 90 °C to 100 °C optionally for example over a period of 5 minutes to 15 minutes, in particular seven minutes in order to accelerate the reaction. Also, the reaction can also be performed at room temperature, with correspondingly more time may be necessary.
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[00033] Colling the heated mixture via water.
[00034] Passing the cooled mixture through cartridge and the waste is
separated and collected in an unbounded product.
[00035] separating the bounded product from the cartridge with the help of ethanol.
[00036] The present invention relates to preparing a radiotracer, comprising the steps of:
- gallium 68 is generated, when HCL is passes through a 68 Ge / 68 Ga-
generator.
- feeding the generated gallium 68 to reactor, wherein the reactor comprises a
buffer and pre cursor, in order to maintain PH value.
- heating, the generated gallium 68 with buffer and pre cursor in the reactor and then cool the heated mixture via water.
– passing, the cooled mixture through cartridge and the waste is separated and collected in an unbounded product.
– separating, the bounded product from the cartridge with the help of ethanol.
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[00037] In order to maintain the pH of the labelling solution in a range where it is possible to ensure solubility, a buffering medium is generally used. The desired buffer must be nontoxic, must effectively maintain the pH within a range of 3.0 to 5.0, should not compete with gallium-68. It must also be able to tolerate possible small changes in the volume of generated gallium-68 (and therefore the amount of HCI), i.e. it must be strong enough to maintain the pH within the desired range with 10% changes in the volume of gallium 68.
[00038] As according to an embodiment of the invention, Generated gallium-68 as described herein, react in the radiolabelling reaction for a short period of time, in particular between about 2 minutes and about 60 minutes, preferably from about 2 minutes to about 30 minutes, for example about 10 minutes.
[00039] As according to an embodiment of the invention,, the radiolabelling reaction is performed in the reactor at a temperature below 50° C, preferably of below 45°C, below 40°C, below 35°C, or below 30°C, most preferably at room temperature, e.g. between 20 and 25°C.
[00040] As according to an embodiment of the invention, the radiolabelling reaction is performed in the reactor at a pH between about 3 and about 5, more preferably between about 3.5 and about 4.5.
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[00041] As according to an embodiment of the present invention, the method perform the radiolabeling reaction at a temperature close to room temperature.
[00042] The invention has several advantages. With this invented method for synthesis of Radiotracer, wherein the Radiotracer is generated in a time and cost efficient manner.
[00043] It is therefore submitted that the instant invention has been shown and described in what is considered to be the most practical and preferred embodiments. It is recognized, however, that departures may be made within the scope of the invention and that obvious modifications will occur to a person skilled in the art. With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in composition, materials, form, function and manner of operation, and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.
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[00044] While in the foregoing specification, several embodiments of the invention have been set forth for purposes of making a complete disclosure, it will be apparent to those skilled in the art that numerous changes may be made without departing from the spirit and principles of the invention.
[00045] Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.

We Claim:

A method for preparing a radiotracer (8), comprising the steps of: - 68 comprising gallium from a 68 Ge / 68 Ga-generator is generated when hydrochloric acid (HCI) is passes through the 68 Ge / 68 Ga-generator;
feeding the generated gallium 68 to a reactor, wherein the reactor comprises a buffer and precursor, in order to maintain PH value.
heating, the generated gallium 68 with buffer and pre cursor in the reactor and then cool the heated mixture via water.
passing, the cooled mixture through cartridge and the waste is separated and collected as an unbounded product.
separating, the bounded product from the cartridge with the help of ethanol.
The method for preparing a radiotracer, of claim 1, wherein the generated gallium-68 with buffer and pre cursor in the reactor react for a short period of time, in particular between about 2 minutes and about 60 minutes, preferably from about 5 minutes to about 15 minutes.
As according to an embodiment of the invention, the radiolabelling reaction is performed in the reactor at a temperature below 50° C, preferably of below 45°C, below 40°C, below 35°C, or below 30°C, most preferably at room temperature, e.g. between 20 and 25°C.
As according to an embodiment of the invention, the radiolabelling reaction

is performed in the reactor at a pH between about 3 and about 5, more preferably between about 3.5 and about 4.5.
5. - A system for preparing a radiotracer, comprising: - a 68 Ge / 68 Ga-generator for generate 68 comprising gallium when hydrochloric acid (HCI) is passes through the 68 Ge / 68 Ga-generator;
A reactor for a radiolabelling reaction of the generated 68 gallium, wherein the reactor comprises a buffer and precursor, in order to maintain PH value.
A cartridge for collect cooled mixture of 68 gallium with buffer and pre cursor, wherein an ethanol is used to separate bounded product from the cartridge.