Article Figures & Data
Figures
- FIGURE 1.
Diagram comparing present one-size-fits-all RPT approach (A) with vision of precision RPTs (B). Central to such a future is development of robust models that translate therapeutic inputs to clinical outputs, from which one can prescribe optimal protocols in cycle 1 and refine the process in later cycles to adaptively optimize treatment.
- FIGURE 2.
RPT is hybridization of 2 therapeutic paradigms, pharmacotherapy and radiation therapy, but with additional element of physiologically mediated delivery that can be imaged through nuclear medicine. Accordingly, CNO may be considered analogous hybrid of pharmacokinetic modeling and radiobiology-calibrated dosimetry, linked via intermediary of image-based internal dosimetry. PD = pharmacodynamics.
- FIGURE 3.
PBPK modeling and simulation from drug discovery and development communities can be applied to enable RPT dosimetry via theranostic principle, which enables estimation of patient-specific pharmacokinetics with pretherapy PET imaging, and use these models to help prospectively predict patient-specific therapeutic doses that can be verified with real-time SPECT imaging. PI = after injection. (PBPK figure adapted from (118), theranostics schematic adapted from (119), diagnostic PET and therapeutic SPECT cartoons adapted from (120), model-parameterized PBRPK network adapted from (8), and time-integrated activity–to–AD diagram adapted from (121).)
- FIGURE 4.
Concepts, tools, and models of external-beam radiobiology, from which much of modern EBRT treatment planning is based, must be modified for RPT because of physiologically mediated small-scale biodistribution and dosimetry, which modify radiation response via series of complex and incompletely understood mechanisms. RPT-adapted radiobiologic modeling must ultimately be paired with suitably estimated multiscale extrapolation to enable robust end-to-end prediction of clinical outcome, illustrated here for the example of acute kidney injury. AKD = acute kidney disease; AKI = acute kidney injury; CKD = chronic kidney disease; CVD = cardiovascular disease; IM = inner medulla; ISOM = inner strip of outer medulla; OSOM = outer strip of outer medulla. (Multiscale anatomy diagrams adapted from (122), acute injury dynamic function schematic adapted from (123), PET/CT adapted from (124), and multiscale dosimetry figure adapted from (125).)
In this issue
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- Article
- Abstract
- REPURPOSING PHYSIOLOGICALLY BASED PHARMACOKINETICS (PBPK) INTO PHYSIOLOGICALLY BASED RADIOPHARMACOKINETICS (PBRPK) FOR PERSONALIZED RPT DOSIMETRY
- RECALIBRATING EBRT RADIOBIOLOGY FOR MULTISCALE RPT DOSIMETRY
- FORWARD-LOOKING VISION: CNO AS A BASIS FOR CROSS-SPECIALTY DIGITAL TWINS
- CONCLUDING THOUGHTS
- DISCLOSURE
- ACKNOWLEDGMENTS
- Footnotes
- REFERENCES
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