Radioembolization with ⁹⁰Y glass microspheres for hepatocellular carcinoma. Significance of pretreatment ¹¹C-acetate and ¹⁸F-FDG PET/CT and posttreatment ⁹⁰Y PET/CT in individualized dose prescription

The aim of this study was to establish an algorithm for the prescription of ⁹⁰Y glass microsphere radioembolization (⁹⁰Y-GMRE) of HCC in individual patients based on the relationship between tumour dose (TD) and response validated by ⁹⁰Y PET/CT dosimetry and dual-tracer PET/CT metabolic parameters. The study group comprised 62 HCC patients prospectively recruited for ⁹⁰Y-GMRE who underwent pretreatment dual-tracer (¹¹C-acetate and ¹⁸F-FDG) PET/CT as surrogate markers of HCC cellular differentiation. Pretreatment tumour-to-nontumour ratio on ^99mTc-MAA SPECT/CT (T/NT_MAA) was correlated with posttreatment ⁹⁰Y PET/CT T/NT_90Y after quantification validation. The TD-response relationship for HCC of different tracer groups was assessed on follow-up PET/CT 2 months after treatment. ⁹⁰Y PET/CT was accurate in the measurement of recovery of injected ⁹⁰Y activity (81.9-99.9%, median 94.8%). Pretreatment SPECT/CT T/NT_MAA was strongly correlated with posttreatment ⁹⁰Y PET/CT T/NT_90Y (5.6 ± 3.2 versus 5.9 ± 3.5, T/NT_90Y 1.01 x T/NT_MAA + 0.161, r = 0.918, P < 0.05). The response rates were 72.4% (21/29), 70.6% (12/17) and 25% (4/16) for well, moderately and poorly differentiated HCC, respectively. The cut-off TD for a good response was significantly different between poorly differentiated and well/moderately differentiated HCC (262 Gy versus 152/174 Gy) with 89.2% sensitivity and 88% specificity. At a limiting tolerated liver dose of 70 Gy, the T/NT_MAA thresholds for predicting a good response in poorly differentiated and well/moderately differentiated HCC were 3.5 and 2.0/2.3. Disregarding HCC cellular differentiation, the cut-off TD became 170 Gy, with lower sensitivity (70.3%) and specificity (76%). ⁹⁰Y PET/CT can provide accurate dosimetry for ⁹⁰Y-GMRE. Pretreatment T/NT_MAA predicts posttreatment T/NT_90Y. The TD thresholds for a good response are tracer-dependent, with a strong correlation between HCC radiosensitivity and cellular differentiation and other PET-based parameters. These cytokinetic factors improve treatment efficacy while minimizing organ damage for the prescription of personalized ⁹⁰Y-GMRE. (orig.)