DNA damage and apoptosis induced by 188Rhenium in tumour cells

Gamma, β + , β - and α emissions of radionuclides can be successfully spoiled in the preparation of radiopharmaceuticals as a useful tool in radiodiagnosis (imaging) and radiotherapy against cancer. For nuclear imaging, 99m Tc has become the “universal” isotope because of its physical characteristics in the field of scintigraphy (6 hours half-life, 140 keV γ emission) [1]. Among the radionuclides the β - emitters are particularly promising in radiotherapy for the capability of their 0.3-2.3 MeV electrons to penetrate tissues in a range of 0.5-12 mm avoiding problems related to cellular internalization of radiopharmaceuticals. 188 Re (16.9 hours half life), a β - and γ emitter similar to the congener 99m Tc, is a promising candidate in nuclear medicine. In fact, while the β - emission (85%, E max = 2.12 MeV) is relevant for therapeutic purposes, the γ-rays (15%, 155 keV) can be detected to evaluate the biodistribution of the radiunuclide. Because of its multiple decay modes, 188 Re might be used for a real-time monitoring of regional drug distribution during radiation therapy. Furthermore 188 Re is available as perrhenate from a 188 W/ 188 Re generator. To date, few data are available in the literature on the sensitivity of different tumour cells to such radionuclide. In this context, the aim of the experiment SCINTIRAD supported by the National Institute for Nuclear Physics (INFN, Italy) is to determine the radio-response of tumour cell lines treated “in vitro” with 188 Re, the biodistribution in different organs of “in vivo” mice and subsequently the therapeutic effect on tumours induced in mice. Furthermore, dedicated devices as an optimized YAP camera for the 188 Re photon spectrum and appropriate software have been developed and improved for imaging of small animals. In particular, we present preliminary results on the genotoxic effect of 188 Re-perrhenate on a panel of human tumour cell lines (U87, H460, MCF-7, LNCaP) in terms of inhibition of cell viability, micronuclei induction and apoptosis.