## 4 Past and Ongoing Biomedical Activities at ISOLDE/Biomedical Research Performed at ISOLDE
### Past Activities
The PET studies with \({}^{86}\)Y-EDTMP constituted the first studies using isotopes produced at CERN that were ever performed in Geneva. The collected activity of \({}^{86}\)Y was rather poor, and even though it allowed for obtaining good bone images of rabbits, it was too low for performing any studies on humans. The observed behavior of \({}^{86}\)Y-EDTMP was as expected: fast blood clearance and non-detectable liver uptake. The PET studies with \({}^{142}\)Sm-EDTMP were, to the best of our knowledge, the first PET scans ever performed with this isotope. \({}^{142}\)Sm-EDTMP exhibited, similarly to \({}^{86}\)Y-EDTMP, a fast blood clearance and undetectable liver uptake. However, the excreted activity was highly accumulated in the bladder [15]. In 1994 the first clinical patient studies with \({}^{83}\)Sr and \({}^{142}\)Sm were performed and the collaboration between the Department of Medical Biochemistry, University of Geneva, and ISOLDE was fully established [16]. The study of the possible use of radioactive ion beams for biomedical research was then extended to a bio-conjugate (chelator-antibody), which is known to have higher tumor specificity: aminooxyacetyl-ferrioxamine coupled to murine anti carcinoembryonic antigen (CEA) IgG1 monoclonal antibody MAB 35, synthesized by [PERSON] and co-workers [17]. The chelator-antibody conjugates were labelled by 2 h incubation in acetate solution with several different lanthanides (\({}^{153}\)Gd, \({}^{169}\)Yb, \({}^{167}\)Tm, \({}^{141}\)Ce) and \({}^{225}\)Ac produced from U-carbide and Ta-foil targets and purified by cation-exchange chromatography column containing \(\alpha\)-hydroxyisobutyric acid (HIB) [18]. The radiolabelled conjugates were then injected into a sample of nude mice bearing xenografted colorectal tumors at the University Hospital in Geneva. The pharmacokinetic behavior of the radionuclides was studied by \(\gamma\)-ray spectroscopy and further compared to \({}^{111}\)In-labelled bio-conjugate with a well-known pharmacokinetic behavior. The obtained results showed that radio-lanthanides exhibit an _in vivo_ behavior similar to clinically used \({}^{111}\)In-labelled immunoconjugates. \({}^{225}\)Ac-labelled conjugates revealed, however, much faster blood clearance, indicating the same insufficient _in vivo_ stability. This series of experiments was concluded by a comparative study of biokinetics of the octreotide peptide linked to aminobenzyl diethylene triamine pentaacetic acid (DTPA) and labelled with \({}^{141}\)Ce, \({}^{143}\)Pm, \({}^{153}\)Gd and \({}^{159}\)Dy and \({}^{111}\)In. For the purpose of this study, bio-conjugates were injected into insulinoma bearing rats at the partner hospital. The obtained results showed a similar tissue uptake for all radio-lanthanides and In and slightly better tumor uptake of the lanthanides-labelled forms [19]. The systematic studies described above aimed at the understanding of the biokinetic behavior of radio-lanthanides and radio-lanthanide-labelled bioconjugates _in vivo_, in order to be able to optimize the conditions for the maximum uptake in the tumor tissue. These studies were followed by experiments aiming at testing several positron emitting lanthanides, which decay to homologue elements that possibly can be used for cancer therapy. Within these studies, it has been shown that, for example, \({}^{152}\)Tb can be used for _in vivo_ dosimetry for monitoring the bio-distribution of \({}^{149}\)Tb in radionuclide therapy [20]. The carrier-free and isotopically clean batches of 500 and 800 MBq of \({}^{152}\)Tb and \({}^{149}\)Tb, respectively, were produced at ISOLDE and then transported to the University Hospital in Geneva, where a Jaszczak phantom was filled with four liters of one activated solution at a time. The comparative PET studies showed significantly better scan quality for \({}^{152}\)Tb (12% positron decay) than for \({}^{149}\)Tb (4% positron decay); however, the energy windows had to be set between 440 and 560 keV in order to reduce the \(\gamma\)-radiation coming from \({}^{152}\)Tb.