Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using 89Zr-ibritumomab tiuxetan and PET

Rizvi, Saiyada N.F.; Visser, Otto; Vosjan, Maria J. W. D.; Lingen, Arthur van; Hoekstra, Otto S.; Zijlstra, Josée M.; Huijgens, Peter C.; Dongen, Guus A.M.S. van; Lubberink, Mark

doi:10.1007/s00259-011-2008-5

Cited by 95 publications

(88 citation statements)

References 22 publications

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“…However, the use of 89 Zr is preferred mainly for tracers with slow kinetics, such as antibodies, because of its long radioactive half-life (3.3 d). This longer half-life inherently results in higher effective doses, such as 0.55 6 0.07 mSv/MBq for 89 Zr-ibritumomab tiuxetan (24). For the present patient group, the absorbed doses due to 68 Ga-ABY-025 should also be seen through the perspective that diagnostic CT scans of the thorax and abdomen will give comparable or higher effective doses.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

et al. 2016

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68 Ga-ABY-025 is a radiolabeled Affibody molecule for in vivo diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors with PET. The aim of the present work was to measure the biodistribution and estimate the radiation dosimetry of 68 Ga-ABY-025 for 2 different peptide mass doses in a single group of patients using dynamic and serial whole-body PET/CT. Methods: Eight patients with metastatic breast cancer were included. Each patient underwent an abdominal 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 4 h after injection of a low peptide dose (LD) and a high peptide dose (HD), with approximately the same amount of radioactivity, in separate investigations 1 wk apart. As input to the absorbed dose calculations, volumes of interest were drawn on all clearly identifiable source organs: liver, kidneys, spleen, descending aorta, and upper large intestine. Absorbed doses were calculated using OLINDA/EXM, version 1.1. Results: Of the major organs, the highest radionuclide uptake at 1, 2, and 4 h after injection was observed in the kidneys and liver. The highest absorbed organ doses were seen in the kidneys, followed by the liver for both LD and HD 68 Ga-ABY-025. Absorbed doses to liver and kidneys were slightly but significantly higher for LD. Total effective dose was 0.030 ± 0.003 mSv/MBq for LD and 0.028 ± 0.002 mSv/MBq for HD. Conclusion: The effective dose for a typical 200-MBq administration of 68 Ga-ABY-025 is 6.0 mSv for LD and 5.6 mSv for HD. Therefore, from a radiation dosimetry point of view, HD is preferred for PET/CT evaluation of HER2-expressing breast cancer tumors. These effective doses are somewhat higher than earlier published values for other 68 Ga-labeled tracers, such as 0.021 ± 0.003 mSv/MBq for 68 Ga-DOTATATE and 68 Ga-DOTATOC, mainly because of higher uptake in liver and kidney. Forwomen,br east cancer is currently the most common cancer.Human epidermal growth factor receptor 2 (HER2) is overexpressed in about 1 of 6 cases (1-3) at initial diagnosis and is associated with poor survival (1,3). Treatments targeted to HER2, such as with the anti-HER2 antibody trastuzumab, have considerably improved overall survival (1,3,4). Today, assessment of HER2 status is based on tumor biopsy. However, HER2 expression can vary between the primary tumor and metastases in up to 40% of cases (2,5,6) and metastatic HER2 expression can change over time, which could necessitate a change of therapy (7,8). Follow-up using biopsies cannot always be performed due to practical reasons or patient discomfort.Molecular imaging using SPECT and PET might be a noninvasive, whole-body-based way to evaluate HER2 expression quantitatively. One such approach is the use of trastuzumab labeled with 111 In (half-time, 2.8 d) (9) or 89 Zr (3.3 d) (10) for use with SPECT and PET, respectively, but the slow kinetics of antibodies require imaging several days after administration. One promising method of fast, safe, and accurate imaging that specifically binds to a site on the receptor not occu...

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Section: Discussionmentioning

confidence: 99%

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

et al. 2016

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“…Rizvi et al (2) reported that, for 89 Zr-ibritumomab tiuxetan, the liver was the organ with the highest absorbed dose (1.36 6 0.58 mGyÁMBq 21 ), followed by the spleen (1.04 6 0.16 mGyÁMBq 21 ), kidneys (0.75 6 0.06 mGyÁMBq 21 ), lungs (0.63 6 0.11 mGyÁMBq 21 ), and RM (0.46 6 0.05 mGyÁMBq 21 ), whereas the effective dose was found to be 0.55 6 0.07 mSvÁMBq 21 . Borjesson et al (19) in a radiation dosimetry study of 89 Zr-cmAb U36 found the highest absorbed dose for the liver (1.30 6 0.34 mSvÁMBq 21 ), followed by the kidneys (1.00 6 0.30 mSvÁMBq 21 ), lungs (0.79 6 0.26 mSvÁMBq 21 ), and spleen (0.72 6 0.18 mSvÁMBq 21 ).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, a recent study showed that the biodistributions of 89 ZrDf-cetuximab and 88 Y-DOTA-cetuximab ( 88 Y as a substitute for 90 Y) were comparable for all organs (1). Another study from the same group demonstrated nearly identical biodistributions of 89 Zribritumomab and 90 Y-ibritumomab (2). Recently, the effect of radioimmunotherapy using 90 Y-cetuximab (combined with external-beam irradiation) on local tumor control in vivo was examined in 3 human squamous cell carcinoma models (3).…”

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PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of ⁸⁹Zr-Cetuximab

Makris¹,

Boellaard²,

Lingen³

et al. 2015

J Nucl Med

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PET/CT imaging allows for image-based estimates of organ and red marrow (RM) residence times. The aim of this study was to derive PET/CT-based radiation dosimetry for 89 Zr-cetuximab, with special emphasis on determining RM-absorbed dose. Methods: Seven patients with colorectal cancer received 36.9 ± 0.8 MBq of 89 Zrcetuximab within 2 h after administration of a therapeutic dose of 500 mgÁm −2 of cetuximab. Whole-body PET/CT scans and blood samples were obtained at 1, 24, 48, 94, and 144 h after injection. RM activity concentrations were calculated from manual delineation of the lumbar vertebrae and blood samples, assuming a fixed RMto-plasma activity concentration ratio (RMPR) of 0.19. The cumulated activity was calculated as the area under the curve of the organ time-activity data (liver, lungs, kidneys, spleen, and RM), assuming physical decay after the last scan. The residence time for each organ was derived by dividing the cumulated activity with the total injected activity. The residence time in the remainder of the body was calculated as the maximum possible residence time minus the sum of residence time of source organs, assuming no excretion during the time course of the scans. The (self and total) RM-and organ-absorbed doses and effective whole-body radiation dose were obtained using dose conversion factors from OLINDA/ EXM 1.1. Several simplified 3-time-point dosimetry approaches were also evaluated. Results: The first approach yielded self and total RM doses of 0.17 ± 0.04 and 0.51 ± 0.06 mGyÁMBq −1 , respectively. The second approach deviated by −21% in self-dose and −6% in total dose. RMPR increased over time in 5 of 7 patients. The highest 89 Zr-absorbed dose was observed in the liver with 2.60 ± 0.78 mGyÁMBq −1 , followed by the kidneys, spleen, and lungs, whereas the effective whole-body dose was 0.61 ± 0.09 mSvÁMBq −1 . The simplified 3-time-point (1, 48, and 144 h) dosimetry approach deviated by at most 4% in both organ-absorbed doses and effective dose. Conclusion: Although the total RM dose estimates obtained with the 2 approaches differed only by at most 6%, the image-based approach is preferred because it accounts for nonconstant RMPR. The number of successive scans can be reduced to 3 without affecting effective dose estimates. PETusi ng long-lived radionuclides has proven to be a valuable tool for predicting the biodistribution of labeled monoclonal antibodies (mAbs) (1,2) and organ dosimetry for radioimmunotherapy (2). In addition, the dose-limiting tissue can be determined, enabling dose escalation and optimization of therapeutic treatment planning. In particular, a recent study showed that the biodistributions of 89 ZrDf-cetuximab and 88 Y-DOTA-cetuximab ( 88 Y as a substitute for 90 Y) were comparable for all organs (1). Another study from the same group demonstrated nearly identical biodistributions of 89 Zribritumomab and 90 Y-ibritumomab (2). Recently, the effect of radioimmunotherapy using 90 Y-cetuximab (combined with external-beam irradiation) on local tumor control in vivo was...

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“…Additionally, it can easily and stably be coupled to monoclonal antibodies (2). To date, all 89 Zr-monoclonal antibody PET/CT studies that have been reported were performed within a single center (3)(4)(5). More recently, several multicenter studies have been initiated.…”

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Multicenter Harmonization of ⁸⁹Zr PET/CT Performance

et al. 2013

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This study investigated the feasibility of quantitative accuracy and harmonized image quality in 89 Zr-PET/CT multicenter studies. Methods: Five PET/CT scanners from 3 vendors were included. 89 Zr activity was measured in a central dose calibrator before delivery. Local activity assays were based on volume as well as on the local dose calibrator. Accuracy and image noise were determined from a cross calibration experiment. Image quality was assessed from recovery coefficients derived from different volume-of-interest (VOI) methods (VOI A50% , based on a 3-dimensional isocontour at 50% of the maximum voxel value with local background correction; VOI Max , based on the voxel with the highest uptake; and VOI 3Dpeak , based on a spheric VOI of 1.2-cm diameter positioned so as to maximize the enclosed average). PET images were analyzed before and after postreconstruction smoothing, applied to match image noise. Results: PET/CT accuracy and image noise ranged from 23% to 10% and from 13% to 22%, respectively. VOI 3Dpeak produced the most reproducible recovery coefficients. After calibration of the local dose calibrator to the central dose calibrator, differences between the local activity assays were within 6%. Conclusion: This study showed that quantitative accuracy and harmonized image quality can be reached in 89 Zr PET/CT multicenter studies. PET using labeled monoclonal antibodies, also known as immuno-PET, shows promise as a tool to predict the outcome of cancer treatment based on monoclonal antibodies (1). Their kinetics dictate the need for a positron label with a long half-life. An ideal radionuclide is 89 Zr (half-life, 78.41 h) because its physical half-life matches the biologic half-life of most antibodies. Additionally, it can easily and stably be coupled to monoclonal antibodies (2). To date, all 89 Zr-monoclonal antibody PET/CT studies that have been reported were performed within a single center (3-5). More recently, several multicenter studies have been initiated. Multicenter studies with 18 F-labeled tracers have shown the need for standardization of image acquisition, reconstruction, and analysis procedures, such as outlined in the European Association of Nuclear Medicine guidelines for tumor imaging (6) and implemented in the form of an accreditation (EANM Research Ltd.[EARL]). For 89 Zr, there are several additional factors that need to be considered: nonprompt emission of 909-keV g rays after each positron emission may influence cross calibration between the local dose calibrator and the PET/CT camera, and low counting rates (due to both low positron abundance and low injected activity) may potentially lead to poorer image quality. The aim of this study was therefore to investigate the feasibility of quantitative accuracy and harmonized image quality in 89 Zr-PET/CT multicenter studies. MATERIALS AND METHODS ScannersThree Gemini TF PET/CT scanners (Philips Healthcare) (7), a Biograph mCT PET/CT scanner (Siemens Medical Solutions) (8), and a Discovery-690 PET/CT scanner (GE Healthcare) (9) were us...

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Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using 89Zr-ibritumomab tiuxetan and PET

Cited by 95 publications

References 22 publications

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of ⁸⁹Zr-Cetuximab

Multicenter Harmonization of ⁸⁹Zr PET/CT Performance

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Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using 89Zr-ibritumomab tiuxetan and PET

Cited by 95 publications

References 22 publications

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients

PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of 89Zr-Cetuximab

Multicenter Harmonization of 89Zr PET/CT Performance

Contact Info

Product

Resources

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Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of ⁸⁹Zr-Cetuximab

Multicenter Harmonization of ⁸⁹Zr PET/CT Performance