Time dependence of the activity concentration ratio of red marrow to blood and implications for red marrow dosimetry

Hindorf, Cécilia; Lindén, Ola; Tennvall, Jan; Wingårdh, Karin; Strand, Sven‐Erik

doi:10.1002/cncr.10291

Cited by 14 publications

(12 citation statements)

References 7 publications

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“…The absorbed dose to the bone marrow was calculated using a bone marrow-to-serum activity concentration ratio valid for macromolecules (0.19), because chromatography indicated that most (.80%) of the 211 At in serum was bound to the antibody fragments. The ratio corresponds to a bone marrowto-blood ratio of 0.32, a value in the range of what has been observed in previous radioimmunotherapy studies (33).…”

Section: Discussionmentioning

confidence: 61%

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

Andersson¹,

Cederkrantz²,

Bäck³

et al. 2009

J Nucl Med

252

201

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The a-emitter 211 At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. Methods: Nine patients underwent laparoscopy 2-5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. 211 At was labeled to MX35 F(ab9) 2 using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with 211 At-MX35 F(ab9) 2 (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. g-camera scans were acquired on 3-5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1-48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. Results: Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% 6 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 6 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 6 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 6 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 6 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 6 1.6 mGy/(MBq/L) (mean 6 SD). No adverse effects were observed either subjectively or in laboratory parameters. Conclusion: This study indicates that by intraperitoneal administration of 211 At-MX35 F(ab9) 2 it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity. The lifetime risk of ovarian cancer is 1%22% in European and U.S. women. Despite seemingly successful cytoreductive surgery, followed by systemic chemotherapy, most patients will relapse and succumb. The relapse is most frequently localized in the abdominal cavity. New systemic chemotherapy regimens have not improved the outcome over the past decade, which prompted experimental intraperitoneal treatments, including radioimmunotherapy.Radioimmunotherapy with b-emitters has displayed promising results, although an international randomized phase III study of 90 Y-HMFG1 showed no improvement in survival or time to relapse (1). This disappointing result could be partly explained by the choice of radionuclide. The long range of this b-emitter results in poor irradiation of small tumor clusters, likely insufficient to eradicate peritoneal micrometastases. Furthermore, the relativel...

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Section: Discussionmentioning

confidence: 61%

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

Andersson¹,

Cederkrantz²,

Bäck³

et al. 2009

J Nucl Med

252

201

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“…In this study, values of Drm were found to be between 60% and 70% of Dwb, which is reasonable considering the modest 350 contribution of the self-absorbed dose and the values for the Swb←wb/Srm←wb ratio. In patients in whom there is red-marrow and/or bone uptake, it is generally recommended to use imagingbased estimates of Drm 26,36,37 , as blood-based values may underestimate the real value.…”

Section: Discussionmentioning

confidence: 99%

Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with ¹³¹I‐metaiodobenzylguanidine with implications for the activity to administer

et al. 2015

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Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with (131)I-metaiodobenzylguanidine with implications for the activity to administer.MINGUEZ GABINA, PABLO; Flux, Glenn; Genolla, Jose; Guayambuco, Sonia; Delgado, Alejandro; Fombellida, Jose Cruz; Sjögreen Gleisner, Katarina , Flux, G., Genolla, J., Guayambuco, S., Delgado, A., Fombellida, J. C., & Sjögreen Gleisner, K. (2015). Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with (131)I-metaiodobenzylguanidine with implications for the activity to administer. Medical Physics, 42(7), 3969-3978. DOI: 10.1118/1.4921807General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Methods: Nine NB patients and six NET patients were included, giving in total 19 treatments as four patients were treated twice. Whole-body absorbed doses were determined from doserate measurements and planar gamma-camera imaging. For six NB and five NET treatments, red-marrow absorbed doses were also determined using the blood-based method.Results: Dosimetric data from repeated administrations in the same patient were consistent. 30In groups of NB and NET patients, similar whole-body residence times were obtained, implying that whole-body absorbed dose per unit of administered activity could be reasonably well described as a power function of the patient mass. For NB, this functional form was found to be consistent with dosimetric data from previously published studies. The whole-2 body to red-marrow absorbed dose ratio was similar among patients, with values of 1.4±0.6 to 35 1.7±0.7 (1 standard deviation) in NB treatments, and between 1.5±0.6 and 1.7±0.7 (1 standard deviation) in NET treatments. Conclusions:The consistency of dosimetric results between administrations for the same patient supports prescription of the activity based on dosimetry performed in pre-treatment studies, or during the first administration in a fractionated schedule. The expressions obtained 40 for whole-body absorbed doses per unit of administered activity as a function of patient mass for NB and NET treatments are believed to be a useful tool to estimate the activity to administer at the stage when the individual patient biokinetics has not yet been measured.

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“…The full expressions of self-dose and cross-dose contribution to the RM can be obtained by substituting Equations 2, 3, and 4 into Equation 6. By introducing a mass scaling for the S factors in Equation 6, the m WB 2 patient terms cancel out and a patient mass-independent term remains, whereas the final cross RM dose term will be patient massdependent.…”

Section: Rm Dose-estimation Methodsmentioning

confidence: 99%

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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Time dependence of the activity concentration ratio of red marrow to blood and implications for red marrow dosimetry

Cited by 14 publications

References 7 publications

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with ¹³¹I‐metaiodobenzylguanidine with implications for the activity to administer

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

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Time dependence of the activity concentration ratio of red marrow to blood and implications for red marrow dosimetry

Cited by 14 publications

References 7 publications

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of 211At-MX35 F(ab′)2—A Phase I Study

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of 211At-MX35 F(ab′)2—A Phase I Study

Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with 131I‐metaiodobenzylguanidine with implications for the activity to administer

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

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Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with ¹³¹I‐metaiodobenzylguanidine with implications for the activity to administer

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