Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial
Clinical question
Can radiopaque yttrium-90 microspheres safely and effectively treat unresectable hepatocellular carcinoma while providing real-time visibility of treatment?
Take away point
Eye90, a radiopaque Y90 microsphere, enables real-time evaluation and treatment adjustment during radioembolization, potentially improving tumor targeting and serving as a tumor response biomarker. Initial study showed 50% complete response at 3 months with no severe adverse events.
Reference
Abraham, R.J., Arepally, A., Liu, D., Lewandowski, R., Kappadath, S.C., Verma, A., Dobrowski, D. and Holden, A., 2024. Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial. Journal of Vascular and Interventional Radiology, 35(10), pp.1464-1473.
Study design
Prospective, observational, descriptive study
Funding Source
ABK Biomedical
Setting
Auckland City Hospital, Auckland, New Zealand
A 53-year-old man with chronic hepatitis B. Axial contrast-enhanced computed tomography (CT) (arterial phase) demonstrated a 4.3-cm Segment 8 hepatocellular carcinoma (white arrow) adjacent to previous transarterial chemo- embolization scar (white arrowhead). CT image demonstrating radiopaque Eye90 microsphere distribution in hepatocellular carcinoma (arrow) and surrounding treated liver volume.
Addressing these challenges, Eye90 Microspheres introduces radiopaque properties for direct CT visualization with a customizable dose with radioactivity between 0.4-9.6 GBq at 3 preset mass ranges: (a) small (100–200 mg), (b)medium (201–400 mg), and (c) large (401–600 mg). Personalized dose vial quantity and activity is determined using a 3-compartment partition model that considers various patient-specific factors based on the technetium-99m macro- aggregated albumin SPECT/CT. This personalized approach reportedly eliminates the need for dose-draw or multiple vials.
Accompanying the Eye90 Microspheres is the Eye90 delivery device, which utilizes a dual-syringe system to achieve a controlled uniform delivery concentration of 60 mg/mL. The delivery device also allows the users to pause, assess microcatheter location with contrast media, examine microsphere distribution using CT modalities, and resume administration as needed.
This study reports 6-month safety, effectiveness, and imageability results for Eye90 in 6 subjects with unresectable HCC (median size of 3.1 cm, range: 1.2 – 4.3 cm). Subjects underwent planning procedure (90Y mapping) followed by selective treatment (≤2 segments) using partition dosimetry by SurePlan LiverY90 aiming to deliver at least 205 Gy and preferably > 250 Gy to the tumor. Post-therapy SPECT/CT, unenhanced lung CT, and 4-phase liver CT within 24 hours of treatment were obtained to correlate microsphere radiopacity with radioactivity. Follow-up were scheduled on days 21, 42, 90, and 180 after treatment.
Post-treatment SPECT/CT demonstrated mean and median dose of 283 Gy and 132 Gy to the tumor, respectively. Microsphere density within the tumor was calculated at 26,988 per mL. All subjects reported adverse events, but no treatment-related Grade ≥3 AEs occurred. At 90 days, 50% achieved complete response (CR) and 33.3% partial response (PR). At 180 days, 50% maintained CR and 16.7% PR. The other patient with PR, and the patient with stable disease at 90 days, underwent TACE and could not be evaluated. Qualitative analysis showed agreement between microsphere radiopacity on CT and radioactivity on SPECT/CT, with CT revealing heterogeneous dose distribution, and absence of radiopacity in the region of a particular tumor despite SPECT/CT activity noted throughout this region. This particular tumor did not respond to treatment.
Figure
A 53-year-old man with chronic hepatitis B. Axial contrast-enhanced computed tomography (CT) (arterial phase) demonstrated a 4.3-cm Segment 8 hepatocellular carcinoma (white arrow) adjacent to previous transarterial chemo- embolization scar (white arrowhead). CT image demonstrating radiopaque Eye90 microsphere distribution in hepatocellular carcinoma (arrow) and surrounding treated liver volume.
Summary
Current 90Y microspheres have limitations. Glass microspheres lack flexibility in quantity and activity customization, often necessitating multiple vials and kits for larger volumes. Resin 90Y provides quantity and activity customization, but at the cost of increased burden on nuclear medicine labs and operator risk. Both microspheres also have limitations in visibility, requiring post-treatment SPECT/ PET for assessing 90Y distribution, tumor targeting, and dosimetry.Addressing these challenges, Eye90 Microspheres introduces radiopaque properties for direct CT visualization with a customizable dose with radioactivity between 0.4-9.6 GBq at 3 preset mass ranges: (a) small (100–200 mg), (b)medium (201–400 mg), and (c) large (401–600 mg). Personalized dose vial quantity and activity is determined using a 3-compartment partition model that considers various patient-specific factors based on the technetium-99m macro- aggregated albumin SPECT/CT. This personalized approach reportedly eliminates the need for dose-draw or multiple vials.
Accompanying the Eye90 Microspheres is the Eye90 delivery device, which utilizes a dual-syringe system to achieve a controlled uniform delivery concentration of 60 mg/mL. The delivery device also allows the users to pause, assess microcatheter location with contrast media, examine microsphere distribution using CT modalities, and resume administration as needed.
This study reports 6-month safety, effectiveness, and imageability results for Eye90 in 6 subjects with unresectable HCC (median size of 3.1 cm, range: 1.2 – 4.3 cm). Subjects underwent planning procedure (90Y mapping) followed by selective treatment (≤2 segments) using partition dosimetry by SurePlan LiverY90 aiming to deliver at least 205 Gy and preferably > 250 Gy to the tumor. Post-therapy SPECT/CT, unenhanced lung CT, and 4-phase liver CT within 24 hours of treatment were obtained to correlate microsphere radiopacity with radioactivity. Follow-up were scheduled on days 21, 42, 90, and 180 after treatment.
Post-treatment SPECT/CT demonstrated mean and median dose of 283 Gy and 132 Gy to the tumor, respectively. Microsphere density within the tumor was calculated at 26,988 per mL. All subjects reported adverse events, but no treatment-related Grade ≥3 AEs occurred. At 90 days, 50% achieved complete response (CR) and 33.3% partial response (PR). At 180 days, 50% maintained CR and 16.7% PR. The other patient with PR, and the patient with stable disease at 90 days, underwent TACE and could not be evaluated. Qualitative analysis showed agreement between microsphere radiopacity on CT and radioactivity on SPECT/CT, with CT revealing heterogeneous dose distribution, and absence of radiopacity in the region of a particular tumor despite SPECT/CT activity noted throughout this region. This particular tumor did not respond to treatment.
Commentary
Eye90 Microspheres represent another advancement in transarterial radioembolization, offering direct visualization of microsphere and tumor targeting on CT modalities. This capability could lead to more precise treatment execution, real-time therapy adjustments, and potentially serve as a biomarker for predicting tumor response and a foundation for more accurate dose-response relationships. The dual-syringe administration system allows for customized quantity and activity of microspheres, enhancing treatment personalization.
While the initial results are promising, the small sample size, short follow-up period, lower-than-planned tumor doses, and mediocre treatment response necessitate further research. The ongoing U.S. Pivotal IDE Route90 trial will provide more comprehensive data on a larger cohort. If these results hold up in larger studies, Eye90 Microspheres could redefine the standard of care in HCC treatment. The potential for improved precision, personalization, and real-time assessment makes this a technology to watch closely in the coming years.
Post author
Leila Haghani, MD
While the initial results are promising, the small sample size, short follow-up period, lower-than-planned tumor doses, and mediocre treatment response necessitate further research. The ongoing U.S. Pivotal IDE Route90 trial will provide more comprehensive data on a larger cohort. If these results hold up in larger studies, Eye90 Microspheres could redefine the standard of care in HCC treatment. The potential for improved precision, personalization, and real-time assessment makes this a technology to watch closely in the coming years.
Post author
Leila Haghani, MD
Research Fellow
University of Massachusetts Chan Medical School
@dr_Leila_IRad
@dr_Leila_IRad
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