Methods and kits for preparing radionuclide complexes

Abstract

A method for preparing a complex comprising a radioisotope of gallium for use in radiotherapy or in a medical imaging procedure, said method comprising adding a gallium radioisotope solution obtained directly from a gallium radionuclide generator to a composition comprising a pharmaceutically acceptable buffer and optionally also a pharmaceutically acceptable basic reagent, in amounts sufficient to increase the pH to a level in the range of 3 to 8, wherein the composition further comprises a chelator that is able to chelate radioactive gallium within said pH range and at moderate temperature, said chelator being optionally linked to a biological targeting agent.

Description

[0001]The present invention relates to methods for preparing radioactive gallium complexes for use in therapy or diagnosis, for example in molecular imaging procedures, to kits for use in these methods, and to novel compositions used in them as well as to methods for molecular imaging and therapy carried out using the compositions or the kits.BACKGROUND TO THE INVENTION[0002]Molecular imaging is a well-known and useful technique for in vivo diagnostics. It may be used in a wide variety of methods including the three-dimensional mapping of molecular processes, such as gene expression, blood flow, physiological changes (pH, etc.), immune responses and cell trafficking. It can be used to detect and diagnose disease, select optimal treatments, and to monitor the effects of treatments to obtain an early readout of efficacy.[0003]A number of distinct technologies can in principle be used for molecular imaging, including positron emission tomography (PET), single photon emission tomography...

AI Technical Summary

Benefits of technology

The invention provides a way to effectively label gallium with a single step, using acidic solutions from (68Ga) radionuclide generators. This simplifies the labeling process and eliminates the need for additional purification steps. The resulting products are physiologically acceptable and have a high level of labeling purity (over95%), which maximizes the available half-life of the radiolabel. This invention provides a convenient and efficient solution for clinical situations that require gallium labeling.

Problems solved by technology

Some hospitals have difficulty with this if they do not have specialist radiochemistry laboratories and therefore their ability to offer treatments such as PET may be restricted.

It may be difficult to prepare radiotracers with sensitive functional moieties.

For example, incorporation of radioisotopes into the radiotracer may involve elevated temperatures that would disrupt protein structure and add undesirable complexity to the labelling process.

However, DOTA has a long radiolabelling time of around 30 to 60 minutes (relative to the half-life of 68Ga ˜68 minutes), which reduces the useful life of the tracer.

In addition, chelation of gallium by DOTA derivatives often requires a high labelling temperature of around 95° C. and acidic pH, which may be damaging to any biological targeting agent associated with the biotracer and adds complexity to the process.

However, a residual problem arises in relation to the radionuclides themselves.

In particular, gallium is liable to precipitate out of solution at neutral to high pH and so requires particular handling.

In many cases, the labelling procedure is also complex.

All this requires complex and dedicated apparatus and the time taken erodes the useful life of the radionuclide.

Such procedures require skilled staff and complex equipment which is not always available.

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