title: PET/CT-derived whole-body and bone marrow dosimetry of 89Zr-cetuximab.
abstract: 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)Zr-cetuximab within 2 h after administration of a therapeutic dose of 500 mg·m(-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 RM-to-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 mGy·MBq(-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 mGy·MBq(-1), followed by the kidneys, spleen, and lungs, whereas the effective whole-body dose was 0.61 ± 0.09 mSv·MBq(-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and n.makris@vumc.nl.
authors.forename: Nikolaos E
authors.initials: NE
authors.lastname: Makris
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Arthur
authors.initials: A
authors.lastname: van Lingen
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Henk M
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Catharina W
authors.initials: CW
authors.lastname: Menke
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Huisman
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011868:Radioisotopes; D011874:Radiometry; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging; D015040:Zirconium
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011868:Radioisotopes; D015040:Zirconium; D000068818:Cetuximab
keywords: 89Zr; PET; absorbed dose; cetuximab; red marrow