Study procedures, activity calculation and dosimetry

The radioembolization procedure was performed over two different sessions: work-up session and treatment session, by the same two interventional radiologists with 5–10 years of experience (between 50–100 procedures per year), following the current standard of practice and according to the manufacturer’s instructions. The work-up evaluation started with an angiography in order to obtain a precise map of the patients’ abdominal vascular anatomy and coil embolization was performed if gastrointestinal branches arising from the hepatic arteries were found.

Patients in group A were treated with ⁹⁰Y activity calculation based on a mono-compartmental dosimetry planning, using a volume based on a ^99mTc-MAA SPECT, after lung shunt fraction evaluation on a whole-body scan. For the standard predictive dosimetry of group A, a calculation sheet from the ⁹⁰Y provider gave us the activity knowing the volume segmented from the ^99mTc-MAA SPECT data (with thresholding based on a maximum intensity percentage of 1%), the lung shunt fraction determined on the whole-body scan (with manual segmentation), and the desired dose to the targeted volume (total perfused volume, based on standard guidelines).

Patients in group B were treated after personalized predictive (multi-compartmental) dosimetry that was performed using Simplicit⁹⁰Y® software. MRI or CE-CT was used for the segmentation of the liver, the tumor, and the non-tumoral liver (manually on MRI, automatically on CE-CT with corrections when needed). Then, ^99mTc-MAA SPECT/CT was co-registered and the perfused volume was determined (with thresholding based on a maximum intensity percentage of 1%) after lung shunt fraction evaluation on the whole-body scan.

Regarding the work-up, for both groups, ^99mTc-MAA were injected after diagnostic angiography in the hepatic artery (with activities between 150 and 200 MBq). Images were performed on a Philips BrightView XCT gamma-camera with a Low Energy High Resolution (LEHR) collimator. First, a whole-body scan was acquired to determine lung shunting (140 ± 14 keV, 18 cm/min, 256 pixels wide). Then, a liver-centered SPECT/CT was conducted to estimate the spatial distribution of the ^99mTc-MAA (140 ± 14 keV, 32 projections, 30 s/projection, 360°, 128 × 128 pixels). The iterative reconstruction method commercially available used is Astonish® (3 iterations, 8 subsets). ^99mTc-MAA lung shunt fraction did not exceed 30 Gy in a single treatment or 50 Gy in case of multiple treatments. In case on an unfavorable ^99mTc-MAA work-up, the procedure was repeated and a solution was searched for (e.g., more selective placement of the catheter during injection to improve the targeting of the lesion). If ⁹⁰Y-based SIRT could not be performed, the patient was treated according to best medical practice. If the work-up had a favorable outcome, the patients were re-admitted for treatment within 15 days.

⁹⁰Y Bremsstrahlung Emission Computed Tomography (⁹⁰Y BECT/CT) post-treatment images were acquired on the same Philips BrightView XCT gamma-camera. An energy window around 120 keV ± 24 keV was chosen to avoid the lead fluorescence X-rays around 80 keV and more energetic photons, eventually passing through the collimator because Medium Energy General Purpose (MEGP) collimator was used. First, a whole-body scan was acquired to visually confirm the absence of lung shunting (120 keV ± 24 keV, 12 cm/min, 256 pixels wide). Then, a liver-centered BECT/CT was conducted to estimate the spatial distribution of the glass microspheres (120 keV ± 24 keV, 64 projections, 30 s/projection, 360°, 64 × 64 pixels). The same commercially available algorithm as previously described was used to reconstruct the data. Those ⁹⁰Y BECT/CT were available for both groups but only used for dosimetry purposes when ⁹⁰Y PET/CT wasn’t available, namely for 18 patients (19 treatments) in group A for dose–response assessment. Regarding this standard predictive dosimetry group 0,42 to 5,1 GBq of ⁹⁰Y were injected.

⁹⁰Y PET/CT post-treatment images used here for dosimetry purposes were acquired on a digital Philips Vereos PET/CT scanner (20 min per bed position for a total of 40 min or 2 bed positions, 288 × 288 pixels of 2 × 2 mm with a slice thickness of 2 mm). The iterative reconstruction algorithm is an Ordered Subset Expectation Maximization (OSEM, 3 iterations, 17 subsets, with Point Spread Function correction option applied) (Trotta 2022). Those ⁹⁰Y PET/CT were available for 9 patients (10 treatments) in group B for dose–response assessment. For this personalized predictive dosimetry group 0,26 to 9,84 GBq of ⁹⁰Y were injected.

⁹⁰Y BECT/CT or ⁹⁰Y PET/CT were co-registered and the perfused volume determined (with thresholding based on a maximum intensity percentage of 1%). Personalized dosimetry was performed using Simplicit⁹⁰Y®. MRI or CECT were used to do the segmentation of the liver, the tumor, and the non-tumoral liver (manually on MRI, automatically on CECT with corrections when needed). Lung shunt fraction was evaluated on a Bremsstrahlung Emission Whole Body scan as described above.

In order to compare the received activity according to standard predictive dosimetry and the activity that would have been recommended by the Simplicit⁹⁰Y® software, only patients in group A for which we disposed of imaging at 3 months after treatment was available, were included. For all of them, CE-MRI, or CECT, ^99mTc-MAA SPECT/CT and ⁹⁰Y BECT/CT have been taken into account.