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PET/MRI Assessment of 90Yttrium Prostate Localization and Acute Response Following Intra-arterial Radioembolization in A Canine Model
Weiguo Li1,2, Kathleen Harris1, Amrutha Mylarapu1, Malcolm Burks1, Simone Raiter1, Vanessa Louise Gates1, Andrew Gordon1, Robert Lewandowski1, Riad Salem1, and Samdeep Mouli1
1Radiology, Northwestern University, Chicago, IL, United States, 2Bioengineering, University of Illinois at Chicago, Chicago, IL, United States

Synopsis

Local-regional therapy of prostate cancer with 90Yttrium (90Y) radioembolization is a novel radiotherapy approach that delivers high-dose radiation therapy with minimal non-target radiation. However, currently no accurate way exists to evaluate radiation effects noninvasively following embolization. In this study, we sought to apply PET/MRI to assess biodistribution of 90Y and estimate effects of treatment following 90Y prostate artery radioembolization in a dog prostate model.

Introduction

Prostate cancer is the third most common cause of cancer-related death in U.S. men[1]. Radical prostatectomy or external beam radiation therapy for patients with high-risk prostate cancer can lead to serious adverse effects including urinary and rectal toxicities [1]. 90Yttrium (90Y) radioembolization offers the potential to deliver high-dose radiotherapy for prostate cancer with minimal non-target radiation[2]. While this novel approach is currently being carried out, evaluation of 90Y radiation effects upon the prostate based on the biodistribution of 90Y following radioembolization is imperative. This preliminary study aimed to assess the biodistribution of 90Y and the relationship to acute response of prostate tissue to 90Y prostate arterial radioembolization using PET/MRI in a dog prostate model.

Methods

Canine model: All the experiments are approved by the Institutional Animal Care and Use Committee. Six male 10-14 kg castrated beagles were treated with hormones for 3 months to generate benign prostatic hypertrophy. Each dog was catheterized through femoral artery under fluoroscopy and 90Y catheterization of the prostatic artery was performed and confirmed by cone beam CT. 90Y microspheres (~100 Gy) were administered.

PET/MRI: Beagles were anesthetized with isoflurane and scanned on the second day (~20 hours) post 90Y arterial administration with a 3T PET/MRI (Biograph mMR, Siemens, Germany). MRI-based attenuation correction was applied using DIXON-VIBE sequences. PET of prostate comprised a 60-min list mode acquisition, during which MRI protocols were performed. Multiparametric MRIs were acquired with diffusion-weighted and dynamic contrast-enhanced (DCE) MRI. Diffusion imaging was performed using a diffusion-weighted SE-EPI sequence with b-values of 400, 600, 800 s/mm2. Gadopentetate dimeglumine was injected intravenously as a rapid bolus (0.1 mmol/kg) at a rate less than 10 mL per 15 seconds. Contrast uptake was followed for 5 minutes with DCE-MRI. The DCE-MRI acquisition consisted of a 3D VIBE dynamic acquisition with TR/TE = 4.47/1.81 ms, FOV=159 x 159 mm2, matrix size = 192 x192, flip angle = 12°, slice thickness = 3 mm, and a temporal resolution of 2.8 sec. PET data was aligned with MR images on Siemens workstation. Image post-processing was performed in MATLAB (MathWorks). Apparent diffusion coefficient (ADC) map was generated with a mono-exponential fitting. Initial area under the curve (IAUC) for Gd was calculated with integration times of 30 and 180 second post–contrast infusion (IAUC30 and IAUC180)[3].

Results

PET/MRI images represent areas of increased radioactivity reflecting the biodistribution of 90Y microsphere (Fig. 1c, and Fig.2a), where 90Y microspheres were found distributed in the treated prostate lobe. Both representative ADC (Fig. 2b) and IAUC30 (Fig. 2c) maps showed a similar pattern as the fused PET/MRI images (Fig. 2a) with enhancement of the treated lobes. However, slight differences were observed as expected. Relative Gd concentration curve (Fig. 2d) showed the 90Y treated regions higher signal enhancement compared to the normal regions with region of interest drawn from fused PET/MRI image. The calculated IAUC values showed changes in treated and control regions of the prostate while those of neighboring muscle remained stable (Fig. 3).

Discussion

The clinical ability to visualize and quantify 90Y microsphere deposition in prostate cancer would benefits dose optimization to maximize tumor kill while limiting adverse effects on normal tissues. Acute phase response of cancer tissue could predict long-term effects of treatment in patients. PET/MRI offers the potential to detect in vivo 90Y biodistribution and simultaneously evaluate tissue response following 90Y arterial radioembolization of the prostate.

Conclusions

With the current study we have demonstrated the potential to build the relationship between tumor 90Y biodistribution and therapeutic response prediction for 90Y radioembolization therapy. Quantitative PET/MRI in future studies intend to quantify localized microsphere concentrations in vivo and correlate with long-term therapeutic effects in order to provide a significant improvement of patient-specific dosimetry associated with 90Y microspheres.

Acknowledgements

ACKNOWLEDGEMENTS: This research was supported by NCI grant Number RO1CA181658 and grant from BTG.

References

1. Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2018. CA Cancer J Clin, 2018. 68(1): p. 7-30.

2. Mouli, S., et al., Y90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation. Journal of Vascular and Interventional Radiology, 2021 (in revision).

3. Chung, W.J., et al., Recurrent Glioblastoma: Optimum Area under the Curve Method Derived from Dynamic Contrast-enhanced T1-weighted Perfusion MR Imaging. Radiology, 2013. 269(2): p. 561-568.

Figures

Fig. 1. Representative T2-, T1-weighted images and image infusion of PET and T2-weighted MR images. A, T2-weighted; B, T1-weighted; and C, fused PET/MRI.

Fig. 2. Representative PET/MR imaging of 90Y treated prostate hyperplasia. A, infused PET image on T2-weighted images; B, ADC maps of the same slice, unit is x10-6 mm2/s; C, IAUC30 maps of the same slice; D, Colored curves showing percentile changes of signal intensity versus time in different prostate regions of the same slice. Simultaneous PET/MRI showing representative biodistribution of 90Y in beagle prostate treated with 90Y arterial radioembolization and acute response of prostate tissue.

Fig. 3. Plots of ADC, IAUC30 and IAUC180 of regions in prostate post 90Y. A, ADC; B, IAUC30; C, IAUC180. Untreated: contralateral control of the prostate; rim: rim of the treated region; center: center of the treated region.

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)
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