Development of a CD8 tracer for in vivo evaluation of CD8

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Development of a CD8 tracer for in vivo evaluation of CD8 T cell tumor infiltration during immunotherapy (Conference Abstract)

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Conference Abstract: Tracer for CD8 T-cell tumor infiltration

Development of a CD8 tracer for in vivo evaluation of CD8 T cell tumor infiltration during immunotherapy (Conference Abstract)

René Raavé, Milou Boswinkel, Gerwin Sandker, Peter Wierstra, Erik H. J. G. Aarntzen, Sandra Heskamp


EMIM 2019, Glasgow: #858. EMIM 2019 Abstracts.

Abstract

Introduction

Immunotherapy is considered a hallmark in cancer treatment by its profound and durable clinical responses in patients with various types of cancer. However, only a subgroup of patients responds to immunotherapy and methods for accurate early response monitoring are lacking. Noninvasive quantitative imaging of CD8+ cytotoxic T cells can provide dynamic and spatial information of anti-tumor response. In the present study we characterized an 111In-labeled anti-mouse CD8 antibody for imaging of tumor infiltrating CD8+ cytotoxic T cells in vitro and in vivo in mice bearing murine CT26 colon tumors.

Methods

An anti-mouse CD8 antibody (clone: YTS 169.4) was randomly conjugated with a 30 times molar excess of NCS-DTPA and radiolabeled with 111In. Using CD8+ TK1 mice lymphoma cells, the immunoreactivity, IC50, internalization and affinity characteristics were determined. CT26 tumor bearing BALB/c mice (10-12 weeks old) were intravenously injected with 8.5 µg (8.5 MBq) [111In]In-DTPA-anti-CD8. One group received an excess of non-radiolabeled CD8 antibody (250 µg). SPECT/CT imaging was performed and organs were collected to quantify tracer uptake at 4h, 24h, 48h and 72h after injection. Autoradiography and immunohistochemistry were performed on paraffin embedded tissue sections of tumor, spleen, lymph nodes and duodenum.

Results/Discussion

In vitro assays demonstrated that the immunoreactive fraction was 44%, IC50 was 1.77 nM, Kd was 3.83 nM, and 6.5% internalization of the total membrane bound activity after 4.5 h of incubation. CD8+ T cell containing organs (lymph nodes, spleen and duodenum) were clearly visible on SPECT scans of mice injected with [111In]In-DTPA-CD8-antibody at all time points. Mice that received an excess of non-radiolabeled CD8-antibody showed most uptake in the spleen. Low to moderate tumor uptake was visible in all groups. Ex vivo biodistribution data confirmed results from SPECT imaging. In the lymph nodes, spleen, duodenum and tumor, an uptake of 38.6 ± 12.3% ID/g (±SD), 87.1 ± 18.0% ID/g, 31.7 ± 16.9% ID/g, and 12.9 ±2.9% ID/g at 24h after injection, respectively. The tumor-to-blood ratio increased from 0.48 at 4h after injection to 2.23 at 72h after injection. Autoradiography and immunohistochemistry confirmed these findings.

Conclusions

The CD8 antibody showed specific uptake in CD8+ T cell containing tissues in vivo, but uptake in the tumor was limited because of presence low number of CD8+ T cells. In the future, this tracer has potential for in vivo evaluation of CD8+ T cell infiltration in tumors and lymphoid tissues before and during immunotherapy.

CONFERENCE ABSTRACT: TRACER FOR CD8 T-CELL TUMOR INFILTRATION
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Evaluation of novel 89Zr chelators and corresponding

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Evaluation of novel 89Zr chelators and corresponding 89Zr-labeled immunoconjugates (Conference Abstract)

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Conference Abstract: Novel 89Zr chelators and immunoconjugates

Evaluation of novel 89Zr chelators and corresponding 89Zr-labeled immunoconjugates (Conference Abstract)

Pierre Adumeau, René Raavé, Christian B. Jacobsen, Gerwin Sandker, Sandra Heskamp, Otto Boerman, Mark Rijpkema, Floriane Mangin, Michel Meyer, Jean-Claude Chambron, Mathieu Moreau, Claire Bernhard, Adrien Dubois, Laurène Da Costa, Victor Goncalves, Franck Denat


EMIM 2019, Glasgow, #654. EMIM 2019 Abstracts.

Abstract

Introduction

For immunoPET with 89Zr, the current gold standard to label antibodies is desferrioxamine (DFO).1 However, preclinical studies have shown that the 89Zr-DFO complex is partly unstable in vivo, leading to 89Zr release and subsequent accumulation in mineral bone. This bone uptake may impede the detection of bone metastases, and hampers accurate estimation of the radiation dose to the bone marrow in dose planning for radioimmunotherapy. Therefore, there is a need for more stable 89Zr chelators.

Methods

We have synthesized new octacoordinating 89Zr-bifunctional chelating agents derivated from the DFO* chelator.2 These new chelators were synthesized by coupling different hydroxamic acid-bearing arms to DFO, followed by the introduction of an isothiocyanate moiety. The model antibody trastuzumab was conjugated to the NCS-derivated chelators and DFO-pPhe-NCS as a reference, and radiolabeled with 89Zr. The stability of the radiolabeled chelators and radiolabeled conjugates were evaluated in human plasma, and in PBS in presence of EDTA or DFO. The in vitro behavior of the most promising compounds was investigated more thoroughly using HER2-experessing SK-OV3 cells, and in vivo distribution was studied in mice with subcutaneous SK-OV3 xenografts by PET/CCT imaging and ex vivo tissue analysis.

Results/Discussion

The bifunctional chelators were conjugated efficiently to trastuzumab. Radiolabeling of the conjugates with 89Zr yielded the radioconjugates with high yield, purity and specific activity (RCY >95%, RCP >99%, SA >100 MBq/mg). When challenged with EDTA or DFO, the 89Zr-chelates and the corresponding radioconjugates displayed an improved stability compared to 89Zr-DFO and 89Zr-DFO-trastuzumab, with the best results obtained for the chelator dubbed cycloDFO*. The immunoreactive fraction and IC50 were similar for 89Zr-DFO-trastuzumab and 89Zr-cycloDFO*-trastuzumab. Internalisation after 2h was significantly higher for 89Zr-cycloDFO*-trastuzumab compared to 89Zr-DFO-trastuzumab. Accumulation of 89Zr in bone was significantly lower for 89Zr-DFO-cyclo*-trastuzumab compared to 89Zr-DFO-trastuzumab in knee (3.6 ± 0.4% vs 5.9 ±0.6%), femur (2.2 ± 0.2% vs 3.4 ± 0.3%), and sternum (3.5± 0.4% vs 4.5 ±0.4%) at 72 h after injection. Uptake in the SK-OV3 tumor was similar for both antibody conjugates.

Conclusions

The new 89Zr-chelators and the associated radioconjugates show improved in vitro stability compared to DFO and 89Zr-DFO-trastuzumab. The radioconjugate derivated from the more promising chelator, 89Zr-cycloDFO*-trastuzumab, demonstrated a better in vivo stability compared to 89Zr-DFO-trastuzumab. Therefore, less radiation exposure to bone marrow and improved bone metastasis detection could be achieved using cycloDFO*.

References

1 S. Heskamp, R. Raavé, O. Boerman, M. Rijpkema, V. Goncalves, F. Denat, Bioconjugate Chem., 2017, 28, 2211-2223.

2 D. Vugts, C. Klaver, C. Sewing, A. Poot, K. Adamzek; S. Huegli, C. Mari, G. Visser, I. Valverde, G. Gasser, T. Mindt, G. van Dongen, Eur. J. Nucl. Med. Mol. Imaging, 2017, 44, 286-295

CONFERENCE ABSTRACT: NOVEL 89ZR CHELATORS AND IMMUNOCONJUGATES
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Direct comparison of the in vitro and in vivo stability

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Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET.

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89Zr-DFO Derivative Stability

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET.

René Raavé, Gerwin Sandker, Pierre Adumeau, Christian Borch Jacobsen, Floriane Mangin, Michel Meyer, Mathieu Moreau, Claire Bernhard, Laurène Da Costa, Adrien Dubois, Victor Goncalves, Magnus Gustafsson, Mark Rijpkema, Otto Boerman, Jean-Claude Chambron, Sandra Heskamp, Franck Denat


European Journal of Nuclear Medicine and Molecular Imaging August 2019, Volume 46, Issue 9, pp 1966–1977 doi:10.1007/s00259-019-04343-2.

 

Abstract

 

Currently, the most commonly used chelator for labelling antibodies with 89Zr for immunoPET is desferrioxamine B (DFO). However, preclinical studies have shown that the limited in vivo stability of the 89Zr-DFO complex results in release of 89Zr, which accumulates in mineral bone. Here we report a novel chelator DFOcyclo*, a preorganized extended DFO derivative that enables octacoordination of the 89Zr radiometal. The aim was to compare the in vitro and in vivo stability of [89Zr]Zr-DFOcyclo*, [89Zr]Zr-DFO* and [89Zr]Zr-DFO.

Methods

The stability of 89Zr-labelled chelators alone and after conjugation to trastuzumab was evaluated in human plasma and PBS, and in the presence of excess EDTA or DFO. The immunoreactive fraction, IC50, and internalization rate of the conjugates were evaluated using HER2-expressing SKOV-3 cells. The in vivo distribution was investigated in mice with subcutaneous HER2+ SKOV-3 or HER2− MDA-MB-231 xenografts by PET/CT imaging and quantitative ex vivo tissue analyses 7 days after injection.

Results

89Zr-labelled DFO, DFO* and DFOcyclo* were stable in human plasma for up to 7 days. In competition with EDTA, DFO* and DFOcyclo* showed higher stability than DFO. In competition with excess DFO, DFOcyclo*-trastuzumab was significantly more stable than the corresponding DFO and DFO* conjugates (p < 0.001). Cell binding and internalization were similar for the three conjugates. In in vivo studies, HER2+ SKOV-3 tumour-bearing mice showed significantly lower bone uptake (p < 0.001) 168 h after injection with [89Zr]Zr-DFOcyclo*-trastuzumab (femur 1.5 ± 0.3%ID/g, knee 2.1 ± 0.4%ID/g) or [89Zr]Zr-DFO*-trastuzumab (femur 2.0 ± 0.3%ID/g, knee 2.68 ± 0.4%ID/g) than after injection with [89Zr]Zr-DFO-trastuzumab (femur 4.5 ± 0.6%ID/g, knee 7.8 ± 0.6%ID/g). Blood levels, tumour uptake and uptake in other organs were not significantly different at 168 h after injection. HER2− MDA-MB-231 tumour-bearing mice showed significantly lower tumour uptake (p < 0.001) after injection with [89Zr]Zr-DFOcyclo*-trastuzumab (16.2 ± 10.1%ID/g) and [89Zr]Zr-DFO-trastuzumab (19.6 ± 3.2%ID/g) than HER2+ SKOV-3 tumour-bearing mice (72.1 ± 14.6%ID/g and 93.1 ± 20.9%ID/g, respectively), while bone uptake was similar.

Conclusion

89Zr-labelled DFOcyclo* and DFOcyclo*-trastuzumab showed higher in vitro and in vivo stability than the current commonly used 89Zr-DFO-trastuzumab. DFOcyclo* is a promising candidate to become the new clinically used standard chelator for 89Zr immunoPET.

89ZR-DFO DERIVATIVE STABILITY
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Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET

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Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET imaging of activated T-cells in humans

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18F-IL2 for clinical PET

Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET imaging of activated T-cells in humans

Elly L. van der Veen, Inês F. Antunes, Petra Maarsingh, Janet Hessels-Scheper, Rolf Zijlma, Hendrikus H. Boersma, Annelies Jorritsma-Smit, Geke A. P. Hospers, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge, Erik F. J. de Vries


EJNMMI Radiopharmacy and Chemistry, Dec 2019, 4,15. doi: 10.1186/s41181-019-0062-7.

Abstract

Background

Molecular imaging of immune cells might be a potential tool for response prediction, treatment evaluation and patient selection in inflammatory diseases as well as oncology. Targeting interleukin-2 (IL2) receptors on activated T-cells using positron emission tomography (PET) with N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL2) could be such a strategy. This paper describes the challenging translation of the partly manual labeling of [18F]FB-IL2 for preclinical studies into an automated procedure following Good Manufacturing Practices (GMP), resulting in a radiopharmaceutical suitable for clinical use.

Methods

The preclinical synthesis of [18F]FB-IL2 was the starting point for translation to a clinical production method. To overcome several challenges, major adaptations in the production process were executed. The final analytical methods and production method were validated and documented. All data with regards to the quality and safety of the final drug product were documented in an investigational medicinal product dossier.

Results

Restrictions in the [18F]FB-IL2 production were imposed by hardware configuration of the automated synthesis equipment and by use of disposable cassettes. Critical steps in the [18F]FB-IL2 production comprised the purification method, stability of recombinant human IL2 and the final formulation. With the GMP compliant production method, [18F]FB-IL2 could reliably be produced with consistent quality complying to all specifications.

Conclusions

To enable the use of [18F]FB-IL2 in clinical studies, a fully automated GMP compliant production process was developed. [18F]FB-IL2 is now produced consistently for use in clinical studies.

18F-IL2 FOR CLINICAL PET
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Tracer kinetic modelling of dynamic Gadoxetate-enhanced MRI

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Tracer kinetic modelling of dynamic Gadoxetate-enhanced MRI (Conference Abstract)

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Conference Abstract: Kinetic modelling of Gadoxetate MRI

Tracer kinetic modelling of dynamic Gadoxetate-enhanced MRI (Conference Abstract)

Steven Sourbron


Hepatocyte Transporter Network Meeting, September 2019. HTNM 2019 Presentation.

CONFERENCE ABSTRACT: KINETIC MODELLING OF GADOXETATE MRI
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Clinical Gd-EOB-DTPA MRI to detect the inhibition

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Clinical Gd-EOB-DTPA MRI to detect the inhibition of hepatocyte transporters (Conference Abstract)

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Conference Abstract: Gadoxetate MRI to see liver transporter inhibition

Clinical Gd-EOB-DTPA MRI to detect the inhibition of hepatocyte transporters (Conference Abstract)

Sirisha Tadimalla


Hepatocyte Transporter Network Meeting, September 2019. HTNM 2019 Presentation.

CONFERENCE ABSTRACT: GADOXETATE MRI TO SEE LIVER TRANSPORTER INHIBITION
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Biological- and imaging biomarkers of oedema and fibrosis

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Biological- and imaging biomarkers of oedema and fibrosis in a rat model of Drug-Induced Interstitial Lung Disease (DIILD) (Conference Abstract)

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IBs of oedema and fibrosis in rat DIILD

Biological- and imaging biomarkers of oedema and fibrosis in a rat model of Drug-Induced Interstitial Lung Disease (DIILD) (Conference Abstract)

Irma Mahmutovic Persson, Hanna Falk Håkansson, Anders Örbom, Per-Ola Önnervik, Janne Persson, Karin Von Wachenfeldt, Lars E. Olsson.


European Respiratory Journal 2019 54: PA2417. doi: 10.1183/13993003.congress-2019.PA2417.

Abstract

A large number of systemically administered drugs have the potential to cause DIILD. We aim to characterize a model of DIILD in the rat and develop imaging biomarkers for detection and quantification of DIILD.

Methods: Sprague-Dawley rats received one single dose of intratracheal bleomycin and were longitudinally imaged at day 0, 3, 7, 14, 21 and 28 post dosing, applying imaging techniques MRI and PET/CT. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein and inflammatory cells. Lungs were taken for further analyses by histology, and stained for inflammation and collagen deposition.

Results: Bleomycin induced significant increase in total protein concentration and total cell count in BALF, peaking at day3 (p>0.001) and day7 (p>0.001) compared to control, respectively. The lesion measured by MRI and the FDG-PET signal in the lungs of bleomycin challenged rats was significantly increased during day3-14, peaking at day7. Two subgroups of animals were identified as low- and high responders to bleomycin challenge, by their different change in total lung volume. Both groups showed signs of inflammation initially, while at later time points the low-responder group recovered towards control, and the high-responder group showed progressive fibrosis with significant increase of lesion volume (p<0.001), compared to control.

Conclusion: Bleomycin-induced lung injury with MRI and PET readout in rats, is an adequate and translational animal model for DIILD studies. The scenario comprised different disease responses, with different fractions of inflammation and fibrosis. Thereby, this study improved the understanding biological- and imaging biomarkers in DIILD.

IBS OF OEDEMA AND FIBROSIS IN RAT DIILD
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Hyperpolarised 129-xenon diffusion-weighted MRI

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Hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

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Conference Abstract: Hyperpolarised 129Xe diffusion-weighted MRI in ILD

Hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

James Eaden, Ho-Fung Chan, Paul Hughes, Nicholas Weatherly, Matthew Austin, Laurie Smith, Jim Lithgow, Andrew Swift, Stephen Renshaw, Maya Buch, Colm Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff Parker, Stephen Bianchi, Jim Wild


European Respiratory Journal 2019 54: PA3157. doi: 10.1183/13993003.congress-2019.PA3157.

Abstract

Introduction: Apparent diffusion coefficient (ADC) is a measure of gas diffusion in the airspaces, where restrictions by tissue boundaries provide information about lung microstructure down to the alveolar level. Diffusion-weighted (DW) MRI of the lung with hyperpolarised helium in idiopathic pulmonary fibrosis (IPF) has shown that ADC correlates with DLCO, KCO and CT fibrosis score (Chan, H-F. et al. Radiology 2019; doi:10.1148/radiol.2019181714) but to date no data are available on the utility of 129-xenon (129Xe) diffusion in interstitial lung disease (ILD). Aim: To evaluate the ability of 129Xe DW-MRI to distinguish between ILD subtypes.

Methods: A prospective, multicentre study of patients with ILD including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), IPF and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe DW-MRI was performed on a 1.5 T scanner and mean ADC was calculated. Results: To date, 33 patients (6 DI-ILD, 7 HP, 15 IPF, 5 CTD-ILD) have undergone baseline 129Xe DW-MRI. There was a significant difference in mean ADC between the ILD subtypes (p=0.011), with the significant difference occuring between the HP (median: 0.038cm2/s) and IPF (median: 0.048cm2/s) groups (p<0.01). Median FVC% predicted in the HP and IPF groups was 75.6% and 84.7% respectively. There was a correlation between mean ADC and DLCO (r=-0.39; p=0.03) as well as KCO (r=-0.58; p<0.01) but not FVC (r=0.24; p=0.19).

Conclusions: We demonstrate a correlation between mean 129Xe ADC and DLCO but not FVC. Our findings suggest significant differences in mean ADC between IPF and HP. Therefore, 129Xe DW-MRI could potentially have a role in differentiating changes in the airway microstructure in ILD subtypes.

CONFERENCE ABSTRACT: HYPERPOLARISED 129XE DIFFUSION-WEIGHTED MRI IN ILD
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Longitudinal change in hyperpolarised 129-xenon MR spectroscopy

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Longitudinal change in hyperpolarised 129-xenon MR spectroscopy in interstitial lung disease (Conference Abstract)

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Conference Abstract: Longitudinal change in hyperpolarised 129Xe MRS in ILD

Longitudinal change in hyperpolarised 129-xenon MR spectroscopy in interstitial lung disease (Conference Abstract)

James Eaden, Paul Hughes, Guilhem Collier, Graham Norquay, Nicholas Weatherly, Matthew Austin, Laurie Smith, Jim Lithgow, Andrew Swift, Stephen Renshaw, Maya Buch, Colm Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff Parker, Stephen Bianchi, Jim Wild


European Respiratory Journal 2019 54: PA3158 doi: 10.1183/13993003.congress-2019.PA3158 .

Abstract

Introduction: Hyperpolarised 129-xenon (129Xe) MR spectroscopy (MRS) can be used as a quantitative marker of gas exchange in interstitial lung disease (ILD). The ratio of the uptake of 129Xe in the red blood cells to the tissue/plasma (RBC:TP) has been shown to be reduced by 70% in idiopathic pulmonary fibrosis (IPF) patients when compared with healthy volunteers (Kaushik, S.S. et al. J Appl Physiol 2014; 117:577-585). In IPF, a significant decline in 129Xe RBC:TP over 12 months has been demonstrated but no significant change in DLCO or KCO (Weatherley, N.D. et al. Thorax 2018 [Epub ahead of print]).

Aim: To compare longitudinal changes in 129Xe RBC:TP with changes in FVC and DLCO between ILD subtypes.

Methods: A prospective, multicentre study of ILD patients including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), IPF and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe MRS was performed on a 1.5 T scanner.

Results: To date, 18 patients (5 DI-ILD, 5 HP, 6 IPF, 2 CTD-ILD) have undergone 129Xe MRS on two separate visits (6 weeks apart for DI-ILD/HP and 6 months apart for IPF/CTD-ILD). There was a significant difference in longitudinal change in RBC:TP between the HP and IPF groups (p=0.022). Median change in RBC:TP in the HP and IPF groups was 0.022 and -0.023 respectively. There was no significant difference in longitudinal change in FVC% predicted (p=0.79) or DLCO% predicted (p=0.39) between the ILD subtypes.

Conclusions: Our findings demonstrate that 129Xe RBC:TP has sensitivity to longitudinal change with significant differences between IPF and HP patients, whilst FVC and DLCO showed no change, suggesting that RBC:TP is more sensitive to change than PFTs in ILD.

CONFERENCE ABSTRACT: LONGITUDINAL CHANGE IN HYPERPOLARISED 129XE MRS IN ILD
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Quantitative CT and hyperpolarised 129-xenon

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Quantitative CT and hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

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Conference Abstract: Quantitative CT and hyperpolarised 129Xe dwMRI in ILD

Quantitative CT and hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

James A. Eaden, Ho-Fung Chan, Paul JC. Hughes, Nicholas D. Weatherly, Matthew Austin, Laurie J. Smith, Jim Lithgow, Smitha Rajaram, Andrew J. Swift, Stephen A. Renshaw, Ronald A. Karwoski, Brian J. Bartholmai, Colm T. Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff JM. Parker, Stephen M. Bianchi, and Jim M. Wild.


Thorax 2019;74:A79. doi: 10.1136/thorax-2019-BTSabstracts2019.131.

Abstract

Introduction: Apparent diffusion coefficient (ADC) is a diffusion-weighted (DW) MRI measure of Brownian gas diffusion in the airspaces, where restrictions by tissue boundaries provide information about lung microstructure. The mean diffusive length scale (LmD), is another DW-MRI lung microstructure measurement calculated using a stretched exponential fit method. Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) quantifies various radiological parenchymal features based on histogram signature mapping techniques and is the most widely used quantitative CT image texture analysis software in interstitial lung disease (ILD).

Aim: To evaluate the ability of hyperpolarised 129-xenon (129Xe) DW-MRI and high resolution CT (HRCT) to distinguish between ILD subtypes.

Methods: A prospective, multicentre study of patients with ILD including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF) and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe DW-MRI was performed on a 1.5 T scanner. The HRCT scan was performed within a year prior to the MRI scan. Quantitative CT analysis was performed using CALIPER. Semi-quantitative visual CT analysis was performed by two consultant chest radiologists using a scoring system (table 1).

Results: To date, 32 patients (7 DI-ILD, 6 HP, 14 IPF, 5 CTD-ILD) have undergone baseline 129Xe DW-MRI and CT analysis. There was a significant difference in LmD between the HP and IPF groups (p=0.048) but this was not observed with ADC (p=0.16). Quantitative CT analysis demonstrated a significant difference between the ILD subtypes in both ground glass (GG) percent (p=0.007) and honeycombing percent (p=0.023), with the significant difference in GG% occurring between the HP and IPF groups (p=0.004). There was no significant difference between the ILD subtypes in reticulation percent (p=0.15). Semi-quantitative visual CT analysis showed a significant difference between the ILD subtypes in GG score (p=0.008), with the significant difference occurring between the HP and IPF groups (p=0.007). There was no significant difference between the ILD subtypes in the reticulation score (p=0.071) or the honeycombing score (p=0.16).

Conclusions: Our findings suggest significant differences in LmD, GG score and CALIPER GG% between IPF and HP. 129Xe DW-MRI and quantitative CT could potentially have a role in differentiating between these ILD subtypes. .

CONFERENCE ABSTRACT: QUANTITATIVE CT AND HYPERPOLARISED 129XE DWMRI IN ILD
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