99mTc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with 166Ho-microspheres

  • Mattijs Elschot
  • Johannes F. W. Nijsen
  • Marnix G. E. H. Lam
  • Maarten L. J. Smits
  • Jip F. Prince
  • Max A. Viergever
  • Maurice A. A. J. van den Bosch
  • Bernard A. Zonnenberg
  • Hugo W. A. M. de JongEmail author
Original Article



Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic 99mTc-macroaggregated albumin (99mTc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of 99mTc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic 166Ho-microsphere imaging and to the actual lung absorbed doses after 166Ho radioembolization.


This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with 166Ho radioembolization. 99mTc-MAA-based and 166Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after 166Ho radioembolization.


In the phantom study, 166Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to −4.4 Gy) than 166Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment 166Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic 166Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of 166Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), 99mTc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and 99mTc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001).


In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic 99mTc-MAA imaging. Pretreatment diagnostic 166Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after 166Ho radioembolization.


Radioembolization Holmium-166 SPECT/CT Lung shunt fraction Radiation pneumonitis 



The clinical studies are registered with (NCT01031784 and NCT01612325). This research project was funded by the Dutch Cancer Society (KWF Kankerbestrijding) under grant UU2009-4346 and by the Dutch Technology Foundation (STW) under grants UGT6069 and OTP06648. M.L.J.S. is supported by a University Medical Center Utrecht Alexandre Suerman MD/PhD grant. We thank T. Bosma for coordinating the study, R. de Roos and A.D. van het Schip for preparing the microspheres, and M. Sarilar, M. Blaauw, D.J. de Vries, R.J. Linssen and H.T. Wolterbeek of the Reactor Institute Delft, Delft University of Technology (Delft, Netherlands) for neutron activation of the microspheres.

Conflicts of interest

J.F.W.N. and B.A.Z. are coinventors of 166Ho-PLLA-microspheres and the patents are assigned to the University Medical Center Utrecht Holding BV. J.F.W.N. is Chief Scientific Officer at Quirem Medical BV.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mattijs Elschot
    • 1
  • Johannes F. W. Nijsen
    • 1
  • Marnix G. E. H. Lam
    • 1
  • Maarten L. J. Smits
    • 1
  • Jip F. Prince
    • 1
  • Max A. Viergever
    • 1
    • 2
  • Maurice A. A. J. van den Bosch
    • 1
  • Bernard A. Zonnenberg
    • 1
  • Hugo W. A. M. de Jong
    • 1
    Email author
  1. 1.Department of Radiology and Nuclear MedicineUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands

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