Out-licensing

Development of a Novel Method to Enhance Tissue Accumulation of Radiolabeled Compounds: Improved Killing of Unwanted Tumour Cells

Introduction/Background

Radiolabelled compounds are used for both tumour detection and tumour therapy. Many tumour cells have a higher density of cell receptors for various circulating compounds than do non-tumour cells; e.g., endocrine tumours show a high density of cell surface receptors for somatostatin, and brain gliomas show a high density of receptors for epidermal growth factor. Thus a radiolabeled compound that binds to these cellular receptors preferentially binds to the tumour cells. Additionally, angiogenesis, the formation of new blood vessels from established microvasculature, is a critical process for tumour growth. Primary tumours and metastases will not grow beyond 2 mm in diameter without an enhanced vascular supply. Angiogenic cells also have a higher density of cell receptors for various circulating compounds than do non-angiogenic vascular tissue; e.g., receptors for both somatostatin and vascular endothelial growth factor are higher in angiogenic tissue. Thus a tumour can also be detected by radiolabeled compounds binding to the angiogenic cells that are closely associated with the tumour cells.

Aims/Hypothesis

Radioimaging and radiotherapy are increasingly important in identifying and killing unwanted tumour cells. The effectiveness of the radioligand depends on the concentration that is accumulated in the target cells. Although methods have been developed to increase the tumour to background ratio, few methods have actually increased the concentration of the radioligand inside either the tumour cells or closely associated angiogenic cells. Thus, there is a need for a method to increase the accumulation and retention of radioligand inside the target cells without an increase in the destruction of normal body cells.

Research

Administration of a radioisotopic compound by infusion over a period of time greater than two hours, preferably greater than twelve hours, greatly increases the maximum radioactivity that accumulates in the target cell. The efficacy of the administration of the radiolabeled compound can be increased about five times higher than prior bolus injection or short infusion methods. This method enhances the tumour to background ratio by increasing the actual radioligand accumulated inside the target cells. This technique works for any radiolabeled compound whose cellular uptake is limited by a cellular process of either binding to a cellular receptor or to a transport protein. Once the radiolabeled compound is bound and internalized, the ability of an unlabeled compound to compete with the radioligand is markedly decreased. The primary factor governing residence time after internalization is the physical half-life of the radioisotope, not biologic half-life.

Conclusion

A method of administering a radioisotopic compound by infusion that can increase efficacy of the administration to about five times higher than prior bolus injection or short infusion methods. This method enhances the tumour to background ratio by increasing the actual radioligand accumulated inside the target cells. This technique works for any radiolabeled compound whose cellular uptake is limited by a cellular process of either binding to a cellular receptor or to a transport protein.

Relevance/Opportunity

We are currently seeking licensing or codevelopment partnerships. Please enquire quoting reference no. 4-97-10.

Preclinical

Issued US Issued Patent # : 6,180,082