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ADVANCES IN RADIOIMMUNOIMAGING AND RADIOIMMUNOTHERAPY
Perkins A. C. 1, Missailidis S. 2
1 Academic Medical Physics, Queen’s Medical Centre The University of Nottingham, Nottingham, UK
2 Department of Chemistry, The Open University Walton Hall, Milton Keynes, UK
Advances in biotechnology have led to new techniques for the design, selection and production of ligands suitable for molecular targeting. One promising approach is the production of specific receptor binding molecules based on defined nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers. The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). Using these techniques, aptamers can now be produced rapidly, inexpensively, and with high homogeneity. Furthermore, they are stable over long term storage at ambient room temperatures. A monomeric aptamer is small in size, with a molecular weight as low as 5 to 10 kDa. However, the aptamer molecule may be used as building block for custom designed targeting agents, offering several advantages. These molecules penetrate tumour readily, reach peak levels quickly and clear from the body rapidly, thus having properties of low toxicity and immunoreactivity. Previous work with radiolabelled aptamers is limited and is currently restricted to preclinical studies, but the body of evidence is steadily growing and aptamers are emerging as valuable clinical products for diagnostic imaging and therapy. We have shown that aptamers directed against the mucin 1 (MUC1) antigen, a tumour marker previously extensively used in tumour imaging and therapy, demonstrated high specificity and uniform penetration in tumour xenografts. The future strategy will be to manipulate the molecular weight of the molecules to achieve an optimum balance between the low immunogenicity and excellent tumour penetration for diagnostic imaging and targeted therapy. In this way, a balance can be achieved between the rapid renal clearance and adequate tumour uptake required for diagnostic imaging and targeted therapy.