18Oxygen Substituted Nucleosides Combined with Proton Beam Therapy: Therapeutic Transmutation In Vitro

• Published in: International journal of particle therapy Vol. 7; no. 4; pp. 11 - 18
• Main Authors: Rich, Tyvin, Pan, Dongfeng, Chordia, Mahendra, Keppel, Cynthia, Beylin, David, Stepanov, Pavel, Jung, Mira, Pang, Dalong, Grindrod, Scott, Dritschilo, Anatoly
• Format: Journal Article
• Language: English
• Published: The Particle Therapy Co-operative Group 01-03-2021; Elsevier
• Subjects: nucleoside; Original; oxygen-18; positron emission tomography (pet); proton therapy; theranostic
• ISSN: 2331-5180; 2331-5180
• DOI: 10.14338/IJPT-D-20-00036.1

PURPOSEProton therapy precisely delivers radiation to cancers to cause damaging strand breaks to cellular DNA, kill malignant cells, and stop tumor growth. Therapeutic protons also generate short-lived activated nuclei of carbon, oxygen, and nitrogen atoms in patients as a result of atomic transmutations that are imaged by positron emission tomography (PET). We hypothesized that the transition of 18O to 18F in an 18O-substituted nucleoside irradiated with therapeutic protons may result in the potential for combined diagnosis and treatment for cancer with proton therapy. MATERIALS AND METHODSReported here is a feasibility study with a therapeutic proton beam used to irradiate H2 18O to a dose of 10 Gy produced by an 85 MeV pristine Bragg peak. PET imaging initiated >45 minutes later showed an 18F decay signal with T1/2 of ∼111 minutes. RESULTSThe 18O to 18F transmutation effect on cell survival was tested by exposing SQ20B squamous carcinoma cells to physiologic 18O-thymidine concentrations of 5 μM for 48 hours followed by 1- to 9-Gy graded doses of proton radiation given 24 hours later. Survival analyses show radiation sensitization with a dose modification factor (DMF) of 1.2. CONCLUSIONSThese data support the idea of therapeutic transmutation in vitro as a biochemical consequence of proton activation of 18O to 18F in substituted thymidine enabling proton radiation enhancement in a cancer cell. 18O-substituted molecules that incorporate into cancer targets may hold promise for improving the therapeutic window of protons and can be evaluated further for postproton therapy PET imaging.