1. Monday Case of the Day A) The treatment was successful: The bremsstrahlung SPECT (Fig 2) indicates that 90 Y was deposited in the tumor. B) The treatment was not successful: The 90 Y PET/CT (Fig 3) shows poor tumor uptake and significant non- target hepatic embolization. C) The treatment was not successful: The bremsstrahlung SPECT (Fig 2) shows radioactivity outside of the liver in the stomach. D) Neither post-treatment image is valid. 90 Y is a pure emitter and cannot be imaged using SPECT or PET. History: Patient with focal intrahepatic cholangiocarcinoma (Fig 1) treated with 90 Y radioembolization. Immediately following 90 Y treatment, a bremsstrahlung SPECT scan (Fig 2) and a PET/CT scan (Fig 3) were acquired. No administrations of radioactivity other than 90 Y were performed on treatment day. Select the best clinical assessment and underlying physical reason. Alexander S. Pasciak, PhD, Austin C. Bourgeois, MD and Yong C Bradley, MD University of Tennessee Medical Center, Knoxville, TN Physics Figure 1 (above): pre- treatment 18 FDG PET acquired 48 hours before treatment. Figure 2 (above): post- treatment bremsstrahlung SPECT Figure 3 (right): post- treatment 90 Y PET/CT

2. Findings: Analysis of the post-treatment bremsstrahlung SPECT appears to indicate 90 Y uptake in the tumor as well as the normal hepatic parenchyma of the left lobe. The bremsstrahlung SPECT also indicates apparent non-target embolization of extrahepatic structures (Figure 2, arrows). Figure 1: pre-treatment 18 FDG PET acquired 48 hours before treatment. Figure 2: post-treatment bremsstrahlung SPECT

3. Findings: Analysis of the post-treatment PET/CT scan shows different result than the post- treatment bremsstrahlung SPECT. The PET scan demonstrates very poor uptake in the tumor (Figure 3, arrow) with the majority of the radioactivity deposition occurring in the normal hepatic parenchyma. The PET does not indicate that there is any extra-hepatic non-target embolization. The activity distribution as indicated by the PET/CT (Figure 3) does not match pre-treatment planning intentions (Figure 1). Figure 1: pre-treatment 18 FDG PET acquired 48 hours before treatment. Figure 3: post-treatment 90 Y PET/CT

4. Diagnosis: (B) The treatment was not successful: The 90 Y PET/CT shows poor tumor uptake and significant non-target hepatic embolization. Figure 1: pre-treatment 18 FDG PET acquired 48 hours before treatment. Figure 3: post-treatment 90 Y PET/CT

5. Discussion: 90 Y can be imaged effectively using PET/CT. In approximately 32 out of every 1 million decays of 90 Y, a positron is emitted through a minor decay branch [1]. A 20 minute post-radioembolization PET/CT scan of the liver is sufficient to produce images which are superior (Figure 3) to traditional bremsstrahlung SPECT imaging of 90 Y (Figure 2). Figure 1: pre-treatment 18 FDG PET acquired 48 hours before treatment. Figure 2: post-treatment bremsstrahlung SPECT Figure 3 (right): post- treatment 90 Y PET/CT

6. Discussion: With positrons emitted by 90 Y in only 32 out of every 1,000,000 decays, how can high quality images be produced? For routine PET/CT imaging using 18 FDG, positrons are emitted in 97% of decays. The low branching fraction for positron emission following decay of 90 Y has the potential to lead to low count rates and noisy images. Figure 3 (right): post-treatment 90 Y PET/CT However, several factors partially make up for this: 1.Higher activities of 90 Y are traditionally used (typically greater than 30 mCi) compared to 18 FDG (10-15 mCi). 2.The activity is concentrated in a much smaller volume (tumor and liver volumes typically less than 1 liter, compared to 18 FDG which is distributed through the whole patient. 3.Modern 4-ring PET/CT scanners can typically image the entire liver with just 1 bed position. A 20-30 minute scan of just the liver is possible in a clinical setting, compared with 2-4 minute bed positions for clinical 18 FDG imaging.

7. Discussion: 90 Y Bremsstrahlung SPECT images acquired with a wide window have poor image quality and are often useful only for confirming that the treatment was delivered to the target lobe (Figure 2). This is primarily due to the large amount of scattered radiation which is included in the images. The excellent resolution and contrast recovery of 90 Y of PET/CT allows the treatment to be localized far more effectively (Figure 3) compared to traditional wide window bremsstrahlung SPECT imaging of 90 Y (Figure 2). 90 Y PET/CT also has the benefit of being quantifiable in a clinical setting, allowing for image based dosimetry [2,3]. Figure 2: post-treatment bremsstrahlung SPECT Figure 3 (right): post-treatment 90 Y PET/CT

8. Clinical Summary: Radioembolization capitalizes upon increased arterial tumor vascularity of a target lesion compared to background liver tissue. Although cholangiocarcinoma is a relatively hypovascular malignancy, this case represents a rare instance in which the target lesion was actually LESS vascular than surrounding normal hepatic parenchyma. Consequently, the tumor-absorbed dose was well below predicted tumoricidal thresholds. The higher spatial resolution of the 90 Y PET/CT allowed for early identification of this treatment failure. In such cases, triage to alternative or adjuvent interventional therapies such as radiofrequency ablation or chemoembolization could help delay progression of disease. Figure 1: pre-treatment 18 FDG PET acquired 48 hours before treatment. Figure 3: post-treatment 90 Y PET/CT

9. References/Bibliography: 1 A. S. Pasciak, A. C. Bourgeois, J. M. McKinney, T. T. Chang, D. R. Osborne, S. N. Acuff and Y. C. Bradley; Radioembolization and the dynamic role of 90Y PET/CT; Front. Oncol; vol. 4:38, 2014. 2 D’Arienzo M, Chiaramida P, Chiacchiararelli L, Coniglio A, Cianni R, Salvatori R, et al. 90Y PET-based dosimetry after selective internal radiotherapy treatments. Nucl Med Commun; vol. 33(6):633–40, 2012. 3 A. S. Pasciak, A. C. Bourgeois and Y. C. Bradley; A comparison of techniques for 90Y PET/CT image-based dosimetry following radioembolization with resin microspheres; Front. Oncol; vol. 4:121, 2014.