• • Researchers screened 25 proprietary degradable glass     compositions (varying radiopacifier loading from 1–17 wt.%) to find formulations that dissolve fully in a tunable timeframe while staying amorphous, processable, and radiopaque for CT visualization.

  • Formulations with 5–13 wt.% radiopacifier achieved complete in vitro degradation within roughly 4–24 hours, with lead candidates reaching post-hydration CT attenuation of ~4,200–6,500 HU (120 kVp) — comparable to or exceeding contrast media benchmarks. Lower radiopacifier loading generally sped up degradation, revealing a tunable tradeoff between how long the embolic stays in place and how radiopaque it is.

• • In an interim analysis of 27 HCC patients treated with radiopaque Eye90 microspheres for 90Y-radioembolization (Route90 trial, NCT05953337), researchers compared post-treatment absorbed dose estimates (Dmean) calculated from CT imaging versus nuclear medicine imaging (SPECT/PET), using a MIRD-based estimate as the reference “ground truth.”
  • For perfused liver volume, CT-based dosimetry showed a much stronger correlation with the MIRD reference  than nuclear medicine did, and CT also had lower bias and better precision. When comparing CT directly against nuclear medicine, correlations were moderate for both perfused volume (R²=0.57) and tumor dose (R²=0.65), and individual patient examples showed sizable dose differences between the two modalities at the tumor level.

• • 4 patients have been successfully treated in the Route90 US IDE pivotal trial for the treatment of unresectable HCC with Eye90 microspheres®.
  • Initial assessment confirms successful Eye90 administration with no serious adverse events.
  • Eye90 provided multi-modality imaging capability on X-ray, CBCT, conventional CT, SPECT/CT and TOF PET/CT and shows promise as an imaging biomarker for predicting tumor response and fiducial for subsequent external beam radiation or radiofrequency/microwave ablation if required.

Nadine Abi-Jaoudeh, M.D. FSIR CCRP,  University of California Irvine

• • Patient personalized dosimetry is feasible
    o Ability to control volume and activity of microspheres.
  • Advanced administration technology enables in-procedure visualized tumor targeting
  • Post procedure precision CT-dosimetry is feasible
  • Future Direction:
    o Real-time CT/CBCT Dosimetry
    o Imaging Biomarker with Radiomics
    o 3D Micro Dosimetry

R J Abraham (1,2), A Verma (2), D Dobrowski (2), A Kulp (3),  A Holden (4), E C Henry (5), S C Kappadath (5), A Syme (6,7), A Arepally (2)

• • Investigational use of CT dosimetry in this study confirms feasibility of determining CT based tumor absorbed dose. Conventional CT provides reduced partial volume effects, reduced respiratory motion artifacts, and an improved depiction of dose heterogeneity which has not been described with usual post Y90 SPECT or PET modalities. These benefits may provide more accurate dose metrics and a better understanding of the dose-response relationship in 90Y therapy.

Robert Abraham MD FSIR FCIRSE FRCPC (1,2), Amit Verma DrPH, MPH (2), Robert Lewandowski MD FSIR (3), David Liu MD FSIR (4), David Dobrowski (2), Andrew Holden MD (5), Aravind Arepally MD FSIR (2)

• Volumetric analysis demonstrated significant contralateral and/or caudate hypertrophy approximately 3 months after selective (≤ 2 segments) Eye90 microsphere® radioembolization with no splenic hypertrophy or evidence of portal hypertension.
• Limitations: Small number of patients and 3-month time point (-> 12 mo.)
• Route 90 US IDE Study planned commencement later this year

Principal Investigator and Presenter: Professor Andrew Holden (1)

• • Primary Endpoints Met
    • Eye90 microspheres treatment was well tolerated
    • No related SAEs have been reported
    • No reports of REILD or RILI
    • 5/6 Patients-CR, 1 patient pending
  • Secondary Endpoints
    • Multi-modality imaging of Y90 MS is feasible: PET, SPECT/CT and Conventional CT
    • Multi-modality dosimetry of Y90 MS is feasible: PET, SPECT/CT and Conventional CT
  • Bonus Endpoints
    • Growth of non treated contralateral liver segments noted- Pending Final Analysis
    • Potential Imaging Biomarker → Targeting and Tracking

Samuel R. Miller, PhD, Shaphan R. Jernigan, MS, Robert J. Abraham, MD, and Gregory D. Buckner, PhD

• •  An in vitro microvascular hepatic tumor model was developed and used to evaluate and compare microsphere administration methods during radioembolization procedures. The transparent planar geometry of this model enables optical assessment of microsphere distributions, and its dynamic perfusion system maintains realistic hepatic pressures and flow rates.
  • The deposition characteristics of yttrium-90 glass microspheres were evaluated for 2 administration methods: conventional bolus delivery and dual-syringe delivery.
  • Administration using a dual-syringe delivery device was associated with more uniform deposition of the microspheres and a higher degree of distal deposition when compared with a bolus delivery device.

Jorge Aramburu, PhD, Raúl Anton, PhD, Macarena Rodríguez-Fraile, MD, PhD, and Jose I. Bilbao, MD, PhD

In its current form, the in vitro platform allows for the analysis of the final microsphere distribution. Incorporating a system to record the dynamic deposition of microspheres would help us better understand how microspheres flow through the arteries and eventually deposit in the in vitro platform.

Robert Abraham, MD, FSIR, FRCPC; Amit Verma; David Dobrowski; Andrew Holden MBChB, FRANZCR, EBIR; Aravind Arepally , M.D., FSIR

• No Evidence of RILD/SAE
• Multimodality Imaging and Dosimetry is feasible
• Noted Contralateral Hypertrophy of Left Lobe
• RO may serve multiple roles

1. 1. 1. 1. Targeting
         2.  Surrogate marker
         3. Provide anatomic contour to monitor tumor morphology

Dr. E. Courtney Henry, MD Anderson Cancer Center

American Association of Physicists in Medicine Annual Meeting 2022
“Best in Physics”

• • Potential benefits of Eye90 microspheres Precision Dosimetry™ include reduced partial volume effects and respiratory motion artifacts, improved visualization of dose distribution, and accurate quantification of dose heterogeneity.
  • Post-treatment CT imaging of imageable microspheres provides the means to perform precision dosimetry and extract more accurate absorbed dose metrics.
  • The strong positive correlation between imageable microspheres and CT-based dosimetry may help physicians with dose-response relationships and improve future patient outcomes.

Robert J. Abraham MD, Dalhousie University

Society of Interventional Radiology Annual Meeting 2022

• • Eye90 microspheres® are in clinical development and are the only imageable Y90 microspheres imageable using X-ray-based imaging technologies.
  • CT-based dosimetry depicts dose heterogeneity with increased accuracy relative to PET-based dosimetry.
  • This approach to dosimetry could provide clinicians with an opportunity to enhance their understanding of the dose-response relationship and improve patient outcomes.
  • The First-in-Human study with Eye90 microspheres® for mCRC and HCC was initiated November 2021 in Auckland, NZ.

Robert J. Abraham MD, Dalhousie University

Society of Interventional Radiology Annual Meeting 2022

• • Eye90 microspheres® is being evaluated in a First-in-Dog HCC Study in partnership with The University of Missouri College of Veterinary Medicine.
  • Here, we describe a case study that evaluated tumor response after Eye90 microspheres administration in a dog patient with HCC.
  • Significant anti-tumor response was noted after six weeks, and the dog underwent a successful left lobectomy.
  • This case shows Eye90 microspheres treatment resulted in a beneficial tumor response, the ability to assess tumor targeting and coverage on CT, and inherent radiopacity correlated well with PET-based radioactivity and tissue histology.

Robert J. Abraham MD, Dalhousie University

Global Embolization Symposium & Technologies Annual Meeting 2022

• • It is a known challenge to evaluate Y90 tumor microspheres deposition in vivo.
  • ABK Biomedical developed a standardized in vitro model, in partnership with NC State University, that captures hepatic vascular anatomy and matches physiologic pressures and flow rates.
  • In this model, the tumor is represented by a branched vascular structure which simulates HCC tumors down to the arteriole level (18µm).
  • Researchers compared in vitro microsphere distribution between the ABK dual-syringe delivery system (DS) and the typical glass Y90 bolus delivery system (BD).
  • The ABK DS system delivered a greater number of glass microspheres penetrating distally, and a more uniform distribution compared to BD.

Dr. E. Courtney Henry, Dalhousie University

Global Embolization Symposium & Technologies Annual Meeting 2021

• • The poor spatial resolution encountered with Y90 PET and SPECT dosimetry underestimates the true dose heterogeneity following radioembolization.
  • Improved estimates of distribution can be obtained with higher resolution dosimetry to accurately quantify dose-response and identify areas at risk of recurrence.
  • The steep dose gradients observed with CT-based dosimetry are highly correlated with radioembolized vasculature because it is directly derived from the microspheres implanted distribution.
  • The strong positive correlation between imageable microspheres and CT-based dosimetry may help physicians with dose-response relationships and improve future patient outcomes.

Dr. Sam Miller, North Carolina State University

Global Embolization Symposium & Technologies Annual Meeting 2021
“Best at GEST” Winner

• Attributes of Y90 distribution in tumors are difficult to observe through in vivo models. This is the first published in vitro model simulating HCC tumors down to the arteriole level (18µm).
• This study compared in vitro microsphere distribution between the ABK dual-syringe delivery system (DS) and a typical glass Y90 bolus delivery system (BD).
• The use of the ABK DS system resulted in a greater number of microspheres penetrating distally compared to BD.
• A more uniform distribution of microspheres was also observed with ABK DS vs BD.
• This study demonstrated that the mode of microsphere delivery affects penetration and uniformity of deposition and may bring a new perspective to Y90 technology development.