'Relationship between thermal dose and cell death for "rapid" ablative and "slow" hyperthermic heating'.
Ter Haar, G
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<h4>Aim</h4>Thermal isoeffective dose (TID) has not been convincingly validated for application to predict biological effects from rapid thermal ablation (e.g., using >55 °C). This study compares the classical method of quantifying TID (derived from hyperthermia data) with a temperature-adjusted method based on the Arrhenius model for predicting cell survival in vitro, after either 'rapid' ablative or 'slow' hyperthermic exposures.<h4>Methods</h4>MTT assay viability data was obtained from two human colon cancer cell lines, (HCT116, HT29), subjected to a range of TIDs (120-720 CEM<sub>43</sub>) using a thermal cycler for hyperthermic (>2 minutes, <50 °C) treatments, or a novel pre-heated water bath based technique for ablative exposures (<10 seconds, >55 °C). TID was initially estimated using a constant R<sub>CEM>43</sub>°<sub>C</sub>=0.5, and subsequently using R<sub>CEM</sub>(T), derived from temperature dependent cell survival (injury rate) Arrhenius analysis.<h4>Results</h4>'Slow' and 'rapid' exposures resulted in cell survival and significant regrowth (both cell lines) 10 days post-treatment for 240 CEM<sub>43</sub> (R<sub>CEM>43</sub>°<sub>C</sub>=0.5), while 340-550 CEM<sub>43</sub> (R<sub>CEM>43</sub>°<sub>C</sub> =0.5) delivered using 'rapid' exposures showed 12 ± 6% viability and 'slow' exposures resulted in undetectable viability. Arrhenius analysis of experimental data (activation energy ΔE = 5.78 ± 0.04 × 10<sup>5</sup> J mole<sup>-1</sup>, frequency factor A = 3.27 ± 11 × 10<sup>91</sup> sec<sup>-1</sup>) yielded R<sub>CEM</sub>=0.42 * e<sup>0.0041*T</sup> which better-predicted cell survival than using R <sub>CEM> 43</sub>°<sub>C</sub>=0.5.<h4>Conclusions</h4>TID calculated using an R<sub>CEM</sub>(T) informed by Arrhenius kinetic parameters provided a more consistent, heating strategy independent, predictor of cell viability, improving dosimetry of ablative thermal exposures. Cell viability was only undetectable above 305 ± 10 CEM<sub>43</sub> using this revised measure.
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Imaging for Radiotherapy Adaptation
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International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2019, 36 (1), pp. 229 - 243