A joint physics and radiobiology DREAM team vision - Towards better response prediction models to advance radiotherapy.

Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in technology, computing, and experimental biology now create opportunities to incorporate this knowledge into enhanced computational models. The ESTRO DREAM (Dose Response, Experiment, Analysis, Modelling) workshop brought together experts across disciplines to pursue the vision of personalized radiotherapy for optimal outcomes through advanced modelling. The ultimate vision is leveraging quantitative models dynamically during therapy to ultimately achieve truly adaptive and biologically guided radiotherapy at the population as well as individual patient-based levels. This requires the generation of models that inform response-based adaptations, individually optimized delivery and enable biological monitoring to provide decision support to clinicians. The goal is expanding to models that can drive the realization of personalized therapy for optimal outcomes. This position paper provides their propositions that describe how innovations in biology, physics, mathematics, and data science including AI could inform models and improve predictions. It consolidates the DREAM team's consensus on scientific priorities and organizational requirements. Scientifically, it stresses the need for rigorous, multifaceted model development, comprehensive validation and clinical applicability and significance. Organizationally, it reinforces the prerequisites of interdisciplinary research and collaboration between physicians, medical physicists, radiobiologists, and computational scientists throughout model development. Solely by a shared understanding of clinical needs, biological mechanisms, and computational methods, more informed models can be created. Future research environment and support must facilitate this integrative method of operation across multiple disciplines.

Biodistribution of anionic separated MDP complexes from different MDP preparations.

The biodistributions of different Tc-MDP complexes, separated from different MDP preparations by anionic exchange chromatography, were investigated. We included MDP preparations from one producer with both ascorbic and gentisic acid as stabilizing agent and one preparation with ascorbic acid from a second producer. Bone to soft tissue ratios in rats were compared for the different Tc-MDP complexes separated. It seems that the elution profile of the radiochromatogram may indicate the biodistribution of the preparation. Ascorbic acid and gentisic acid caused different elution profiles and the different complexes isolated were demonstrated to have different bone to muscle ratios.

Determination of the oxidation state of 99mTc in complexes with MDP and DTPA.

The oxidation state of technetium-99m, reduced by concentrated hydrochloric acid and evaporation until dryness, was determined by radiochromatography. The dry deposits of reduced 99mTc were allowed to react with DTPA and MDP with and without antioxidants present. The formation of 99mTc(IV)-DTPA and 99mTc(IV)-MDP complexes and the influence of the antioxidants gentisic and ascorbic acids were studied by radiochromatography and by biodistributional studies in rabbits. 99mTc(IV)-MDP complexes thus formed were demonstrated to have the same biodistribution in rabbits as 99mTc-MDP complexes formed by a conventional stannous reduction kit technique.