Application of 3D printed phantoms to preclinical radiotherapy and PET imaging studies. Dr. Christopher Cawthorne

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1 Application of 3D printed phantoms to preclinical radiotherapy and PET imaging studies Dr. Christopher Cawthorne

2 Preclinical Radiotherapy The aim of preclinical experimentation is to understand how to improve the effectiveness of radiotherapy in clinical practice Two major overall goals: Identify drug targets for combination therapy and understand MOA Develop tools for patient stratification for targeted therapy and the measurement of response

3 Preclinical Radiotherapy Day et al. Cell, 2015 Use of orthotopic/gemm cancer models to better mimic clinical situation

4 Preclinical Radiotherapy State of the art radiotherapy platforms can mimic clinical IMRT and IGRT delivery approaches University of Leeds Preclinical dosimetry is currently non-standardised (or completely lacking) Radiation response curves are typically steep, and dose uncertainty leads to high variation/large number of animals

5 Preclinical Radiotherapy Radiation response curves are typically steep, and dose uncertainty leads to high variation/large number of animals Need for physically accurate phantom to assess delivered dose.

6 Preclinical Dosimetry phantom Project outline: segment CT images of mouse into bone/lung/soft tissue Derive STL files for 3D printing skeleton and body for moulding

7 Preclinical Dosimetry phantom Skeleton embedded in vacuum-cast mould derived from print of whole mouse Mould filled with gelatin to re-create whole body Density of 3D printed material not high enough to mimic bone

8 Preclinical Dosimetry phantom A range of tissue-equivalent materials were evaluated for fabrication 3D printing of bone-density material combined with CNC milling of lung insert and moulding of body

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10 Preclinical Dosimetry phantom Evaluation of morphology and density via CT

11 Preclinical Dosimetry phantom Evaluation of morphology and density via CT

12 Preclinical Dosimetry phantom Evaluation of morphology and density via CT

13 relative response Preclinical Dosimetry phantom Evaluation of passive detectors for dosimetry ongoing reading:1,2 Aug 2017 (Co-60) reading:3,4 Aug 2017 (Co-60) reading:8 Aug 2017 (Co-60) reading:15 Aug 2017 (Co-60) reading:17 Aug 2017 (Co-60) TLD #

14 Preclinical Imaging with PET Development of imaging biomarkers: Defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention". (Atkinson et al., 2001) Diagnostic/prognostic biomarkers predictive of patient outcome Predictive biomarkers predictive of patient outcome in response to a particular therapy, enabling patient stratification Response biomarkers early readouts of drug efficacy in clinical trials PET is has unlimited depth and is thus translatable

15 Preclinical Imaging with PET Imaging of mouse cancer models (similar to radiotherapy models) Quantitation in PET is dependent on many factors: size of ROI vs resolution of scanner, image reconstruction Positron ranges differ between isotopes, affecting resolution and % annihilation in different tissues Although scatter is negligible in a single mouse, this is not the case for multiple animal scanning Standard phantom (NEMA-NU4) suited to general figures of merit Need for physically accurate phantom to assess accuracy of image quantitation

16 Preclinical PET phantom Project outline: assess PSF in tissue equivalent material Incorporate voids for radioisotope addition to 3D-printed tissue equivalent phantom Tissue equivalent materials provided by Leeds Test objects: Lung inhale Lung exhale Water eq. Lung inhale (PU330) Lung exhale (PU450) Water equivalent (WT1) Trabecular bone (HA50) Cortical bone (SB5) Trabecular bone Cortical bone

17 Preclinical PET phantom 0.4 mm syringe 0.2 mm capillary 10 mm Mean Positron range for: 18 F = 0.56 mm 68 G = 2.57 mm 0.2 mm external diameter silica capillary with 0.1 mm internal diameter to minimize positron annihilation

18 Preclinical PET phantom 18 F 9.00 radial profile distribution (mm) FWHM FWTM FWThM Lung inhale Lung exhale Water equivalent Trabecular bone Cortical Bone

19 Preclinical PET phantom 68 Ga radial profile distribution (mm) FWHM FWTM FWThM Lung inhale Lung exhale Water equivalent Trabecular bone Cortical Bone

20 FWHM (MM) Preclinical PET phantom 68 Ga: FBP vs OSEM 3.50 Full width at Half Maximum (mm) Lung inhale Lung exhale Water equivalent Trabecular bone Cortical Bone FBP OSEM

21 FWHM (MM) FWHM (MM) Preclinical PET phantom 68 Ga: FBP vs OSEM Full width at Tenth Maximum (mm) Full width at Twentieth Maximum (mm) Lung inhale Lung exhale Water equivalent Trabecular bone Cortical Bone FBP Lung inhale Lung exhale Water equivalent Trabecular bone Cortical Bone FBP OSEM OSEM

22 Preclinical PET phantom Density also affects quantitation!

23 Preclinical PET phantom Phantom design to assess quantitative effects of reconstruction Plastic phantom recapitulated 3 areas of uptake seen in animals, regions filled independently with typical activity levels

24 Preclinical PET phantom

25 Acknowledgements Giuseppe Schettino Anna Subiel Sanjiv Mooneram Georgios Soultanidis Nikos Efthymiou John Greenman Vicky Green Craig Moore Time Wood Andy Beavis Amanda Tulk Adrian Walker Funding: