Use of Radioactive Ion Beams for Biomedical Research 1. in vivo labelling of monoclonal antibodies with radio-lanthanides and $^{225}$Ac

% IS330 \\ \\\begin{enumerate} \item The aim of this study was to contribute to developments of new radiopharmaceuticals for tumour diagnosis and therapy. CERN-ISOLDE is the leading facility in the world to provide radioactive ion beams with high selectivity, purity and intensity. Radioisotope production by spallation makes available a complete range of rare earth isotopes having as complete a diversity of types and energy of radiation, of half-life, and of ionic properties as one would wish. The availability of exotic nuclei, e.g. radionuclides of rare earth elements and $^{225}$Ac, opens new possibilities for the development of radiopharmaceuticals for diagnosis and therapy.\\ \\ \item Two approaches were followed within the experimental program. The radioactive metal ions are bound either to bio-specific ligands (monoclonal antibodies or peptides) or to unspecific low molecular weight form. The aim of the experimental program is to evaluate relationships between physico-chemical parameters of the tracer molecule (such as complex stability, structure, ionic radius, concentration, etc.) and the corresponding biological behaviour (expressed in clearance, biodistribution, ratio of enrichment, tumor uptake, therapeutic efficacy, etc.).\\ \\ \item Results \\ The biokinetic behaviour of EDTMP (EDTMP = ethylenediamine- tetramethylene phosphonic acid) has been studied simultaneously in combination with different radioisotopes of rare earth elements and $^{225}$Ac. A strong influence of the concentration of the chelating ligand on the biodistribution has been measured. Low molecular weight chelating ligands give a wide scope for influencing the biodistribution of carrier free radio-lanthanides. Already tumor-to-liver ratios of about 10 have been obtained for tumor-bearing mice.\\ \\DTPA substituted anti-CEA monoclonal antibodies have been successfully labelled with radiolanthanides. They show promisingly high in vivo stability and high tumor uptake. The new labelled bio-conjugates show approximately the same biological behaviour as is known for $^{111}$In labelled monoclonal antibodies. Also $^{225}$Ac could clearly be incorporated into the protein fraction. In this case, however, the in vivo stability is far from satisfactory. New chelators must be found in order to increase the binding stabiltiy of the $^{225}$Ac.\\ \\Systematic biokinetic studies have been performed with succinylaminobenzyl-DTPA\\ \\Octreotide (a peptide consisting of a special sequence of 8 aminoacids) labelled with different lanthanides have been performed. The in vivo stability of the new bioconjugates was in all cases satisfactory. High tumor-to-liver ratios suggest the use of the new group of tracers in systemic radionuclide therapy, however the kidney uptake is very high. New molecule designs will overcome this problem.\\ \\\item The experiments will be continued in the frame of a new experiment and an extended collaboration.\\ \\\\ \\\\ \\\\ \\