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Binding Studies of 111Ag to Macrocyclic Thioethers: The First Step to New Radioimmunoconjugates for Cancer Therapy B. Cortecka, C. Lippert, X. Ni, W. Tröger, T. Butz Systemic target radiotherapy is a systemic treatment of mostly cancer in which a radioisotope is selectively taken up due to the high affinity of either the radionuclide or its carrier to the affected tissue. Besides the selective tissue uptake of the radionuclide also its nuclear properties (half-life, emitted radiation) have to be considered for its therapeutic use. Pure or almost pure b- emitters are most widely used due to the convenient range of b- radiation in tissue (few mm) which allows to deposit most or even all radiation to the treated tissue without damaging the surrounding normal tissue. 32P (t1/2=14.4 d), 67Cu (t1/2=2.6 d),89Sr (t1/2=50 d), 131I (t1/2=8 d), and 153Sm (t1/2=1.9 d) are most frequently used for this pupose. 111Ag (t1/2=7.5 d) which decays with 93% probability to the groundstate of 111Cd would be another useful therapeutic isotope. Since 111Ag exhibits no tissue selectivity like 131I (thyroid) or 89Sr (skeleton) it has to be conjugated to a carrier such as peptides, hormones or antibodies which can be used for tumour targeting. The carriers are either labelled with the radioisotope directly or with a chelating agent containing the radioisotope. In the case of 111Ag derivatized hexadendate macrocyclic thioethers (...18S6(OH), 19S6(OH), 20S6(OH)...) are used as chelating ligands which are coupled to antibodies via an OH-group. In order to monitor the complexation of 111Ag by the macrocyclic thioether the (95-247) keV g-g-cascade in 111Cd (populated by approximately 1% of the decays) is used to detect the nuclear quadrupole interaction (NQI) via time differential perturbed angular correlation (TDPAC). Besides the structural information on the binding site of the complexed radioisotope derived by the NQI the rotational correlation time tc of the NQI provides quantitative information on the binding of the 111Ag- chelator complex to the antibody due to mass variations. In this way also the selectivity of the antibody binding to tumour tissue can be checked. Due to the extreme sensitivity of the TDPAC method (1011 to 1012 radioisotopes are sufficient) these studies can be easily performed in the regime of trace amouts used for clinical applications which is almost inaccessible for other techniques used for metal speciation.
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