Towards a personalised theranostics platform through an improved understanding of the biological effects of radionuclide therapy

Abstract

The clinical incorporation of radiobiology into theranostic nuclear medicine for cancer treatment is still an emerging field. The complexities involved in personalising therapy using radionuclides must be investigated from a cellular level, to improve treatment outcomes and predict dose response for patients. This thesis studied an unexplored therapeutic use of an easily accessible diagnostic radionuclide, 18F, which demonstrated a maximum in vitro cell kill effect of up to 90% at 30 Gy in a radioresistant prostate cancer cell line, LNCaP C4- 2B. The relative biological effectiveness of 0.42 was observed at 50% cell survival, when compared to an external beam x-ray irradiation. The dose rate effects that heavily impact the repair probability of cells were also manipulated for the 18F irradiation, showing a maximum of 12% difference in the cell survival at 15 Gy between a G-factor difference of 0.7 and 0.9, triggering cell cycle arrest in the G2/M phase. Finally, using 177Lu patient images, two dosimetry software platforms, OLINDA/EXM and MIM Encore, were compared in a proof-of-concept biodistribution and activity prescription of 64Cu, 68Ga and 18F, giving MIM/OLINDA activity ratios between 0.5 and 3.5 for six organs of interest. These studies collectively attempted to build a foundation for the personalisation of theranostics in nuclear medicine, while exploring novel modes of therapy using radionuclides with multiple decay pathways.