First steps in the preparation of 188Re-based radiopharmaceuticals

1. INTRODUCTION Rhenium-188 is a promising radionuclide for radiotherapeutic applications. It emits β- particles with a maximum energy of 2.12 MeV, suitable for deep tissue penetration (≥ 1 cm) [2]. In addition, it emits a 155 keV γ-ray (15 %) [2], which can be used for imaging with current SPECT (single-photon emission computed tomography) systems. However, several high-energy γ-rays in emission spectrum of 188Re, together with radiation produced by β--particles (Bremsstrahlung), may complicate quantitative imaging. Another challenge is the selection of a proper chelator for 188Re complexation, as rhenium, like technetium (Tc), offers complex coordination chemistry according to their numerous oxidation states. 2. MATERIALS AND METHODS Simulations have been performed to obtain spectra of detected events in simple SPECT systems, to distinguish particles’ origin or scatter factor, both with 99mTc and 188Re point sources. GATE software (Geant4 Application for Tomographic Emission) was used to execute Monte Carlo simulations. A point source (3.7 MBq, 100 µCi) was placed in the middle of phantom cylinder (2 cm radius) filled with water. The single-crystal NaI detector (50×50×4 mm) was positioned in front of the source at 7 cm (center of the detector plane). Simulations were run for 60 seconds. Mercaptoacetyltriglycine (MAG3) was selected as a reference chelator for radiolabelling. Influence of the temperature and concentrations of N Ethyl N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and of 2,3,5,6-tetrafluorophenol (TFF) were tested with 99mTc. 3. RESULTS AND DISCUSSION Results of the simulations show that effect of high-energy γ-rays from the 188Re spectrum is negligible in these simple systems. However, for short distances between the source and the detector – e. g. in preclinical systems – detection of the primary β--particles is possible, which may contribute up to 20 % of the events. Simulations with more complex systems, including various phantoms and collimators, are necessary for verification. Results will be compared also by phantom studies on small animal imaging SPECT systems. In radiolabelling, concentration effect at room temperature is corresponding to already reported data [1]. Yields obtained at higher temperature are lower, therefore heating the reaction mixture is counter-productive in this case. Results of these studies are promising for future development of 188Re-labelled radiopharmaceutical and related imaging protocols. References [1] Gomez de Castiglia, S. et al., "Optimization of biomolecules labelling with Rhenium-188 using direct and indirect methods," IAEA, Vienna, Austria, 2003. [2] Hafeli, U. O. et al., "Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres after neutron-activation," Applied Radiation and Isotopes, 54, 869 - 879, 2001.