Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy.
BACKGROUND
Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity.


METHODS
RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a (177)Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after (177)Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for (177)Lu-based pretargeted RIT and simulated pretargeted RIT with (90)Y.


RESULTS
3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with (90)Y instead of (177)Lu.


CONCLUSIONS
3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. wietske.woliner-vanderweg@radboudumc.nl.
Wietske
W
Woliner-van der Weg
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. rafke.schoffelen@radboudumc.nl.
Rafke
R
Schoffelen
Department of Radiology, Johns Hopkins University, Baltimore, MD, USA. rhobbs3@jhmi.edu.
Robert F
RF
Hobbs
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. martin.gotthardt@radboudumc.nl.
Martin
M
Gotthardt
Immunomedics, Inc., Morris Plains, NJ, USA. dmg.gscancer@att.net.
David M
DM
Goldenberg
Immunomedics, Inc., Morris Plains, NJ, USA. rmsharkey@Immunomedics.com.
Robert M
RM
Sharkey
University of Twente, Enschede, The Netherlands. c.h.slump@utwente.nl.
Cornelis H
CH
Slump
Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. winette.vandergraaf@radboudumc.nl.
Winette Ta
WT
van der Graaf
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. wim.oyen@radboudumc.nl.
Wim Jg
WJ
Oyen
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. otto.boerman@radboudumc.nl.
Otto C
OC
Boerman
Department of Radiology, Johns Hopkins University, Baltimore, MD, USA. gsgouros@jhmi.edu.
George
G
Sgouros
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. Eric.Visser@radboudumc.nl.
Eric P
EP
Visser