## 4 Past and Ongoing Biomedical Activities at ISOLDE/Biomedical Research Performed at ISOLDE  
### Past Activities  
The first biomedical research ever performed with the use of radionuclides produced at ISOLDE is dated to as early as 1979, when a batch of around 70 MBq (2 mCi) of \({}^{167}\)Tm was produced, transported to Dresden, Germany, labelled with citrate and then injected into a patient suffering from a lymphoma cancer [8,9]. After that, in the early 1980s, a novel \({}^{81}\)Rb-\({}^{81}\)Kr generator for medical use was developed based on the specific behavior of the noble gases implanted into a tape used in the tape transport collection devices existing at that time at ISOLDE and Dubna. In the test experiment performed at ISOLDE in 1983, \({}^{81}\)Rb ions were implanted into several host materials, such as Mylar foils, filter paper, polyethylene foil and aluminum foil [10]. The \({}^{81}\)Rb implanted foils (4 MBq each) were then mounted at the end of a small gas tube and fixed to a Ge(Li)-detector. For each foil, four different tests were performed: (1) a measurement with no gas in the tube; (2) a measurement with an air stream passing through the tube; (3) a measurement with water as an eluent; and (4) physiological NaCl as the eluent. The obtained results showed above 85% release efficiency of \({}^{81}\)Kr from the Mylar foils with different thicknesses and the polyethylene foil, whereas, the efficiency for Al foil did not exceed 5%. Unexpectedly  
Figure 4: Reproduction of the isotope mass separator installed at the CRC at Louvain La Neuve. The beam switchyard shown on the right allows one to perform three batch collections in parallel (courtesy [PERSON] CRC-KU Leuven). high quantity \({}^{81\rm{m}}\)Kr elution was obtained for both water and NaCl (above 95%), thus demonstrating a possible medical application of the \({}^{81\rm{Rb}}\)-\({}^{81\rm{m}}\)Kr generator for use _in vivo_. The next biomedical activities based on the isotopes produced at ISOLDE were reported nearly a decade later (1990-1993) when [PERSON] _et al_. investigated the influence of EDTMP (ethylenediamine tetra(methylene phosphonic acid) chelator concentration on the bio-distribution of simultaneously injected different radio-lanthanides and \({}^{225}\)Ac in mice bearing carcinoma tumor [11, 12, 13]. For the purpose of these studies, carrier-free and isotopically clean samples of \({}^{145}\)Sm, \({}^{147}\)Eu, \({}^{149}\)Gd, \({}^{153}\)Gd and \({}^{167}\)Tm were produced by the interaction of 1 GeV protons with a Ta-foil target and those of \({}^{141}\)Ce, \({}^{147}\)Nd, \({}^{147}\)Eu and \({}^{225}\)Ac from a U-carbide target. The isotopes were implanted into foils and then recovered in the process of radiochemical purification. The highly concentrated (\(>\)50 MBq/mL) samples of a volume of 10 \(\mu\)L each containing 0.05 M HCl were next shipped to the University Hospital in Geneva, where the final solution preparation took place. The cocktail solutions (0.5 mL) containing different concentrations of EDTMP and about 50 kBq of each isotope were then injected into 30 tumor-bearing mice. The studies of individual bio-distribution of each radio-lanthanide and Ac chelated by EDTMP revealed, on the one hand, much lower liver uptake for all used radio-metals as compared to the citrates and almost no affected tumor uptake, on the other. Consequently, better tumor-to-liver uptake ratios were obtained for all radio-lanthanide and Ac. These ratios, however, turned out to be to a large extent affected by the concentration of the chelating ligand, showing the same close correlation between the ligand concentration and the bio-distribution of metal-chelate complexes _in vivo_. Subsequently, two positron emitting isotopes, \({}^{86}\)Y (Nb-target) and \({}^{142}\)Sm (U-carbide target), were collected in 1993, chelated by EDTMP and, finally, used for quantitative bone imaging in rabbits with a rotating PET (positron emission tomography) scanner at the Department of Radiology, Nuclear Medicine, University of Geneva [14].