Abstract
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Background: Since the development of positron emission tomography (PET) imaging in the 1950s, positron emitting radionuclides have been used extensively in diagnostic medicine. Due to the focus on positrons in the diagnostic setting, the therapeutic potential of positron emitters has been overlooked. This study demonstrates the first cytotoxic in vitro evidence of the positron emitter 18F on the prostate cancer cell line LNCaP C4-2B.
Methods: A clonogenic assay protocol determining the cell survival was designed to benchmark the effect of positron emitters against X-ray therapy. Cells were grown in a flask for 3 days, then administered with a measured initial activity concentration of 18F ranging from 26.2 to 78.6 MBq/mL to achieve 10 to 30 Gy for an 18-hour irradiation, before removing the radioactive media for plating. For the X-ray irradiation, the 225 kVp Small Animal Radiation Research Platform (SARRP, Xstrah Inc, Atlanta, Georgia, USA) was used on the open-field setup (20 x 20 cm2), and the administered dose ranged from 0 to 7.5 Gy in 2.5 Gy increments. The plated cells were incubated for 7 days before staining. The cell survival data was obtained using a vSpot Spectrum EliSpot reader (Autoimmun Diagnostika GmbhH, Strassberg, Germany). Results: A substantial cell kill (approximately 70 % at 10 Gy) by the positron emitter 18F was revealed from the clonogenic assay (Figure 1). Previous in vitro studies in literature using β- emitting radionuclides such as 90Y or 177Y have shown less than 30 % cell kill in a range of different cell lines using 10 Gy, indicating a therapeutic significance for positron emitters. The positron RBE obtained from the benchmark against X-ray irradiation was 0.42, calculated at 0.5 survival fraction. This low RBE calculated from the cell survival curve can be attributed by the difference in dose rate of over 200-fold between the two modalities (7 to 21 mGy/min versus 4.5 x 103 mGy/min for positrons and X-rays respectively). Figure 1: LNCaP C4-2B Clonogenic Cell Survival Curve: 18F positron emission versus SARRP X-ray. Black dotted line depicts the mean absorbed dose required to reduce cell survival fraction to 0.5. Conclusion: The results demonstrated the first in vitro evidence of the therapeutic effect of positron emitters, with an attractive prospective for future studies. The relatively short half-life, along with the cost, availability and reduced imaging time for using positron emitters in therapy justifies attempts to find ways to overcome certain limitations such as the radiation protection and logistics in the administration of the high activities. Furthermore, as the results indicate a higher efficacy compared to the currently used therapeutic β- emitting radionuclides, a potential theranostic role of positron emitters could be established in the near future.
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