Prognostic Utility of 90Y Radioembolization Dosimetry Based on Fusion 99mTc-Macroaggregated Albumin–99mTc-Sulfur Colloid SPECT

Planning hepatic 90Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping. Methods: Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of 99mTc-macroaggregated albumin (99mTc-MAA) to simulate subsequent 90Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid (99mTc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the 90Y radiation absorbed dose to functional liver tissue (DFL) by calculation of 99mTc-MAA activity in regions with 99mTc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of 99mTc-MAA activity in voxels without 99mTc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy. Results: Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05). Conclusion: Dual-tracer 99mTc-MAA–99mTc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

[1]  A. Benson,et al.  Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. , 2007, International journal of radiation oncology, biology, physics.

[2]  Lidia Strigari,et al.  Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with 90Y-SIR Spheres: Radiobiologic Considerations , 2010, The Journal of Nuclear Medicine.

[3]  M. A. Bosch,et al.  Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis , 2009, European Radiology.

[4]  F. Izzo,et al.  Survival after yttrium‐90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: A European evaluation , 2011, Hepatology.

[5]  B. Sangro,et al.  Radioembolization in the Treatment of Unresectable Liver Tumors: Experience Across a Range of Primary Cancers , 2012, American journal of clinical oncology.

[6]  S. Gulec,et al.  Dosimetric techniques in 90Y-microsphere therapy of liver cancer: The MIRD equations for dose calculations. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  Wenzheng Feng,et al.  Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies. , 2011, Medical physics.

[8]  B. Sangro,et al.  Liver disease induced by radioembolization of liver tumors , 2008, Cancer.

[9]  G. van Hazel,et al.  Randomised phase 2 trial of SIR‐Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer , 2004, Journal of surgical oncology.

[10]  M. Anscher,et al.  Hepatic toxicity resulting from cancer treatment. , 1995, International journal of radiation oncology, biology, physics.

[11]  Y. Kao,et al.  Clinical implications of the body surface area method versus partition model dosimetry for yttrium-90 radioembolization using resin microspheres: a technical review , 2011, Annals of nuclear medicine.

[12]  J. Geschwind,et al.  Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations , 2007, CardioVascular and Interventional Radiology.

[13]  W. Lau,et al.  Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. , 2012, International journal of radiation oncology, biology, physics.

[14]  B. Tan,et al.  Image-Guided Personalized Predictive Dosimetry by Artery-Specific SPECT/CT Partition Modeling for Safe and Effective 90Y Radioembolization , 2012, The Journal of Nuclear Medicine.

[15]  Y. Rolland,et al.  Dosimetry Based on 99mTc-Macroaggregated Albumin SPECT/CT Accurately Predicts Tumor Response and Survival in Hepatocellular Carcinoma Patients Treated with 90Y-Loaded Glass Microspheres: Preliminary Results , 2012, The Journal of Nuclear Medicine.

[16]  G. Lichtenstein,et al.  Hepatic scintigraphy in the evaluation of solitary solid liver masses. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  B. Sangro,et al.  General Selection Criteria of Patients for Radioembolization of Liver Tumors: An International Working Group Report , 2011, American journal of clinical oncology.

[18]  S. Nag,et al.  Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. , 2009, International journal of radiation oncology, biology, physics.

[19]  B. Sangro,et al.  Radioembolization for Hepatocellular Carcinoma: A Review of the Evidence and Treatment Recommendations , 2011, American journal of clinical oncology.

[20]  V. Gebski,et al.  Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.