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 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...

Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach

“…The original design consisted of four treatment arms (two with cisplatin and two with cetuximab) all preceded by an 89 Zr-cetuximab pre-treatment imaging step which was solely used for research purposes. The use of a long-lived positron emitter complicated procedures for the radiotherapy departments, patients were confronted with an extra radiation burden (0.61 mSv/MBq [31]) and additional guidelines had to be followed by the patient during two weeks after injection to limit radiation exposure to others. The resulting slow accrual in combination with discontinuation of the funding of cetuximab resulted in an amendment of the trial excluding 89 Zr-cetuximab PET/CT imaging and the cetuximab treatment arms.…”

Extracellular domain shedding influences specific tumor uptake and organ distribution of the EGFR PET tracer 89Zr-imgatuzumab

“…89 Zr-labeled antibodies have also been developed for preclinical EGFR imaging [13–15]. Furthermore, clinical EGFR imaging has been performed with 89 Zr-cetuximab in advanced colorectal cancer patient [16,17]. Additional clinical studies are currently ongoing for both 89 Zr-cetuximab and 89 Zr-panitumumab (ClinicalTrial.gov identifiers NCT01691391, NCT02117466 and NCT02192541).…”

Recombinant Human Thyroid-Stimulating Hormone Versus Thyroid Hormone Withdrawal in124I PET/CT–Based Dosimetry for131I Therapy of Metastatic Differentiated Thyroid Cancer

“…In this study, it was assumed that the activity concentration within the VOI was uniform and no further corrections were applied to account for differences in activity concentration or density within the VOI. Previous studies by Schwartz et al (26) and Makris et al (27) have applied a correction to the red marrow activity concentration for the trabecular bone component, assuming that the activity concentration in the trabecular bone was zero. This assumption is reasonable when there is no specific binding to bone components, which is true for the radiolabeled antibodies used in these 2 studies (26,27).…”

“…Previous studies by Schwartz et al (26) and Makris et al (27) have applied a correction to the red marrow activity concentration for the trabecular bone component, assuming that the activity concentration in the trabecular bone was zero. This assumption is reasonable when there is no specific binding to bone components, which is true for the radiolabeled antibodies used in these 2 studies (26,27). Another study by Shah et al (28) provided a detailed modeling of the 3-dimensional small-scale structure of individual marrow-containing bones within the skeleton and presented estimates of absorbed fractions and S values for a variety of b-emitters.…”