Radiopharmaceutical solutions with advantageous properties

Abstract

Methods and solutions are describes whereby radiopharmaceutical radium-224 solutions are added complex for scavenging daughter nuclide, which may enhance the overall targeting and reduces uptake of daughter nuclide in normal tissues and cells. This is accomplished without reducing the bone targeting ability of radium. The methods and solutions are convenient to use since the complexation of daughter nuclide can be done in situ in a ready to use radiopharmaceutical solution or, depending on the activity concentration, in a simple kit format by mixing two solutions and store the mixture for typically 1 minute to a few hours before administration to a patient. The use of targeted chelate scavengers for 224Ra daughter nuclide opens up the possibility for using 224Ra based solutions for medical treatments.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]The present invention relates to a radiopharmaceutical solution comprising 224Ra and a complex capable of scavenging 212Pb and / or 212Bi. This solution can be used for medical purposes, including treatment of cancer. Further aspects of the invention relates to kits and methods for providing specific solutions.[0003]2. Description of the Related Art[0004]Targeted alpha particle radionuclide therapy holds promise as therapeutic modality against malignant and non-malignant diseases. Alpha-emitting radionuclides are highly cytotoxic and the alpha particles produced are of high linear energy, which is delivering a high amount of ionization over a short range, causing destruction of DNA by a high degree of irreparable double strand breaks.[0005]Thus, it is important when using alpha emitting radionuclides that they do reach the target and are not released from the targeting compound and that they do not produce longer lived da...

AI Technical Summary

Benefits of technology

The present invention provides a radiopharmaceutical solution containing 224Ra and a complex capable of scavenging at least 212Pb. The complex can be a chelator, cryptands, crown ethers, porphyrins, or polyphosphonates. The 212Pb and / or 212Bi can be complexed by bone-seeking EDTMP. The complexing agent can be conjugated to a compound such as a monoclonal or polyclonal antibody, an antibody fragment, synthetic protein, peptide, vitamin, or vitamin derivative. The invention also provides a kit comprising a radiopharmaceutical solution and a neutralizing solution, and a method of treating skeletal disease by administering the radiopharmaceutical solution to an individual in need. The method also includes a method for providing a 224Ra solution by mixing chelate labeled protein or peptide with a solution of 224.

Problems solved by technology

Alpha-emitting radionuclides are highly cytotoxic and the alpha particles produced are of high linear energy, which is delivering a high amount of ionization over a short range, causing destruction of DNA by a high degree of irreparable double strand breaks.

Thus, it is important when using alpha emitting radionuclides that they do reach the target and are not released from the targeting compound and that they do not produce longer lived daughter nuclides that diffuse away from the mother nuclide, since this can cause toxicity in remote tissues.

It is a challenge in the field to find a radionuclide with appropriate half life, decay properties, chemical properties and daughter products that are suitable for development of medical treatments.

Although reintroduced after the development of improved purification methods for a brief period about year 2000, its use was finally abandoned partly due to fear of late effects and the appearance of new treatment options for AS.

Therefore 224Ra is not in use as a radiopharmaceutical today and is not considered among the plausible candidates for alpha therapy by leading experts in the field.

There is, however, research going on using 224Ra loaded wires for local intratumoral brachytherapy / radon diffusion therapy but they are not using aqueous 224Ra solutions for therapy.

Such purification is impractical since it would require laborious procedures to be performed at the hospital where the product is being used or that the production and use is being geographically restricted.

Probably to a significant extent because of this short product shelf life (in addition to increased competition with the new drugs for AS) and the thereby logistics and supply constraint the product has been discontinued.

Dissolved 224Ra salt has previously been tested in cancer therapy but was abandoned because of unfavorable properties and ineffectiveness.

Therefore it is known in the field that 224Ra has unfavorable daughter nuclide restricting its use in radiopharmaceutical solutions.

Radium-223 used against bone metastases today is a pure bone-seeker and do not address the problem of CTC's.

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