In Vivo Dosimetry Based on SPECT and MR Imaging of 166Ho-Microspheres for Treatment of Liver Malignancies

166Ho-poly(l-lactic acid) microspheres allow for quantitative imaging with MR imaging or SPECT for microsphere biodistribution assessment after radioembolization. The purpose of this study was to evaluate SPECT- and MR imaging–based dosimetry in the first patients treated with 166Ho radioembolization. Methods: Fifteen patients with unresectable, chemorefractory liver metastases of any origin were enrolled in this phase 1 study and were treated with 166Ho radioembolization according to a dose escalation protocol (20–80 Gy). The contours of all liver segments and all discernible tumors were manually delineated on T2-weighted posttreatment MR images and registered to the posttreatment SPECT images (n = 9) or SPECT/CT images (n = 6) and MR imaging–based R2* maps (n = 14). Dosimetry was based on SPECT (n = 15) and MR imaging (n = 9) for all volumes of interest, tumor-to-nontumor (T/N) activity concentration ratios were calculated, and correlation and agreement of MR imaging– and SPECT-based measurements were evaluated. Results: The median overall T/N ratio was 1.4 based on SPECT (range, 0.9–2.8) and 1.4 based on MR imaging (range, 1.1–3.1). In 6 of 15 patients (40%), all tumors had received an activity concentration equal to or higher than the normal liver (T/N ratio ≥ 1). Analysis of SPECT and MR imaging measurements for dose to liver segments yielded a high correlation (R2 = 0.91) and a moderate agreement (mean bias, 3.7 Gy; 95% limits of agreement, −11.2 to 18.7). Conclusion: With the use of 166Ho-microspheres, in vivo dosimetry is feasible on the basis of both SPECT and MR imaging, which enables personalized treatment by selective targeting of inadequately treated tumors.

[1]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[2]  L. Shen,et al.  Apparent diffusion coefficient: potential imaging biomarker for prediction and early detection of response to chemotherapy in hepatic metastases. , 2008, Radiology.

[3]  E. Merkle Spiral and multislice computed tomography of the body , 2004 .

[4]  M. A. van den Bosch,et al.  Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver: technical aspects studied in a large animal model , 2009, European Radiology.

[5]  H. Bierman,et al.  Studies on the blood supply of tumors in man. III. Vascular patterns of the liver by hepatic arteriography in vivo. , 1951, Journal of the National Cancer Institute.

[6]  M. A. van den Bosch,et al.  Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. , 2012, The Lancet. Oncology.

[7]  Diego R Martin,et al.  Imaging of liver metastases: MRI , 2007, Cancer imaging : the official publication of the International Cancer Imaging Society.

[8]  S. Gulec,et al.  Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio , 2007, Journal of Translational Medicine.

[9]  Uulke A. van der Heide,et al.  Simultaneous multi-modality ROI delineation in clinical practice , 2009, Comput. Methods Programs Biomed..

[10]  J. Thrall,et al.  Definition of hepatic tumor microcirculation by single photon emission computerized tomography (SPECT). , 1984, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  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.

[12]  P. Seevinck,et al.  Magnetic resonance imaging-based radiation-absorbed dose estimation of 166Ho microspheres in liver radioembolization. , 2012, International journal of radiation oncology, biology, physics.

[13]  C. Nutting,et al.  Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. , 2004, International journal of radiation oncology, biology, physics.

[14]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[15]  R. Stubbs,et al.  Relationship of 99mtechnetium labelled macroaggregated albumin (99mTc-MAA) uptake by colorectal liver metastases to response following Selective Internal Radiation Therapy (SIRT) , 2005, BMC nuclear medicine.

[16]  W E Bolch,et al.  MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  Chris J G Bakker,et al.  Liver tumors: MR imaging of radioactive holmium microspheres--phantom and rabbit study. , 2004, Radiology.

[18]  Chris J G Bakker,et al.  Fully MR‐guided hepatic artery catheterization for selective drug delivery: A feasibility study in pigs , 2006, Journal of magnetic resonance imaging : JMRI.

[19]  Freek J Beekman,et al.  Hybrid scatter correction applied to quantitative holmium-166 SPECT , 2006, Physics in medicine and biology.

[20]  M. Viergever,et al.  MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation , 2012, European Radiology.

[21]  R. Wahl,et al.  From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors , 2009, Journal of Nuclear Medicine.

[22]  Peter R Seevinck,et al.  Factors affecting the sensitivity and detection limits of MRI, CT, and SPECT for multimodal diagnostic and therapeutic agents. , 2007, Anti-cancer agents in medicinal chemistry.

[23]  J. Seppenwoolde,et al.  Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  H. de Jong,et al.  Quantitative Evaluation of Scintillation Camera Imaging Characteristics of Isotopes Used in Liver Radioembolization , 2011, PloS one.

[25]  A. Li,et al.  Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin. , 1997, The British journal of radiology.

[26]  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.

[27]  P. V. van Rijk,et al.  Holmium-166 poly lactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: effects of preparation and neutron activation techniques , 1999, European Journal of Nuclear Medicine.

[28]  Michael Ljungberg,et al.  Development and evaluation of an improved quantitative (90)Y bremsstrahlung SPECT method. , 2012, Medical physics.

[29]  P. Flamen,et al.  Multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolization therapy with Yttrium-90 labeled resin microspheres , 2008, Physics in medicine and biology.

[30]  M. Prokop,et al.  Spiral and multislice computed tomography of the body , 2003 .

[31]  M. A. van den Bosch,et al.  Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial , 2010, Journal of experimental & clinical cancer research : CR.

[32]  P. V. van Rijk,et al.  Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application. , 2006, International journal of pharmaceutics.

[33]  S. Walrand,et al.  Dosimetry of yttrium-labelled radiopharmaceuticals for internal therapy: 86Y or 90Y imaging? , 2011, European Journal of Nuclear Medicine and Molecular Imaging.