Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy

Wietske Woliner-van der Weg*, Rafke Schoffelen, Robert F. Hobbs, Martin Gotthardt, David M. Goldenberg, Robert M. Sharkey, Cornelis H. Slump, Winette T.A. van der Graaf, Wim J.G. Oyen, Otto C. Boerman, George Sgouros, Eric P. Visser

*Corresponding author for this work

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    Abstract

    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 177Lu-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 177Lu 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 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. 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 90Y instead of 177Lu. 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.

    Original languageEnglish
    Article number5
    Pages (from-to)1-14
    Number of pages14
    JournalEJNMMI physics
    Volume2
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2015

    Fingerprint

    Radioimmunotherapy
    bone marrow
    Dosimetry
    dosimeters
    planning
    Tumors
    Bone
    tumors
    Bone Marrow
    Planning
    dosage
    Neoplasms
    blood
    grade
    Blood
    Therapeutics
    cranium
    toxicity
    Toxicity
    Thrombocytopenia

    Cite this

    Woliner-van der Weg, W., Schoffelen, R., Hobbs, R. F., Gotthardt, M., Goldenberg, D. M., Sharkey, R. M., ... Visser, E. P. (2015). Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. EJNMMI physics, 2(1), 1-14. [5]. https://doi.org/10.1186/s40658-014-0104-x
    Woliner-van der Weg, Wietske ; Schoffelen, Rafke ; Hobbs, Robert F. ; Gotthardt, Martin ; Goldenberg, David M. ; Sharkey, Robert M. ; Slump, Cornelis H. ; van der Graaf, Winette T.A. ; Oyen, Wim J.G. ; Boerman, Otto C. ; Sgouros, George ; Visser, Eric P. / Tumor and red bone marrow dosimetry : comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. In: EJNMMI physics. 2015 ; Vol. 2, No. 1. pp. 1-14.
    @article{e3970109d4f1491580620422481f3ad4,
    title = "Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy",
    abstract = "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 177Lu-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 177Lu 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 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. 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 90Y instead of 177Lu. 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.",
    author = "{Woliner-van der Weg}, Wietske and Rafke Schoffelen and Hobbs, {Robert F.} and Martin Gotthardt and Goldenberg, {David M.} and Sharkey, {Robert M.} and Slump, {Cornelis H.} and {van der Graaf}, {Winette T.A.} and Oyen, {Wim J.G.} and Boerman, {Otto C.} and George Sgouros and Visser, {Eric P.}",
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    language = "English",
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    journal = "EJNMMI physics",
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    Woliner-van der Weg, W, Schoffelen, R, Hobbs, RF, Gotthardt, M, Goldenberg, DM, Sharkey, RM, Slump, CH, van der Graaf, WTA, Oyen, WJG, Boerman, OC, Sgouros, G & Visser, EP 2015, 'Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy', EJNMMI physics, vol. 2, no. 1, 5, pp. 1-14. https://doi.org/10.1186/s40658-014-0104-x

    Tumor and red bone marrow dosimetry : comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. / Woliner-van der Weg, Wietske; Schoffelen, Rafke; Hobbs, Robert F.; Gotthardt, Martin; Goldenberg, David M.; Sharkey, Robert M.; Slump, Cornelis H.; van der Graaf, Winette T.A.; Oyen, Wim J.G.; Boerman, Otto C.; Sgouros, George; Visser, Eric P.

    In: EJNMMI physics, Vol. 2, No. 1, 5, 01.12.2015, p. 1-14.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Tumor and red bone marrow dosimetry

    T2 - comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy

    AU - Woliner-van der Weg, Wietske

    AU - Schoffelen, Rafke

    AU - Hobbs, Robert F.

    AU - Gotthardt, Martin

    AU - Goldenberg, David M.

    AU - Sharkey, Robert M.

    AU - Slump, Cornelis H.

    AU - van der Graaf, Winette T.A.

    AU - Oyen, Wim J.G.

    AU - Boerman, Otto C.

    AU - Sgouros, George

    AU - Visser, Eric P.

    PY - 2015/12/1

    Y1 - 2015/12/1

    N2 - 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 177Lu-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 177Lu 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 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. 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 90Y instead of 177Lu. 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.

    AB - 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 177Lu-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 177Lu 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 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. 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 90Y instead of 177Lu. 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.

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    Woliner-van der Weg W, Schoffelen R, Hobbs RF, Gotthardt M, Goldenberg DM, Sharkey RM et al. Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. EJNMMI physics. 2015 Dec 1;2(1):1-14. 5. https://doi.org/10.1186/s40658-014-0104-x