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

Abstract

Purpose

Positron emission tomography (PET) with ⁸⁹Zr-ibritumomab tiuxetan can be used to monitor biodistribution of ⁹⁰Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of ⁹⁰Y-ibritumomab tiuxetan in humans on the basis of ⁸⁹Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of ⁹⁰Y-ibritumomab tiuxetan influences biodistribution of ⁸⁹Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with ⁸⁹Zr-ibritumomab tiuxetan can be used to predict biodistribution of ⁹⁰Y-ibritumomab tiuxetan and the dose-limiting organ during therapy.

Methods

Seven patients with relapsed B-cell non-Hodgkin’s lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of ~70 MBq ⁸⁹Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg ⁹⁰Y-ibritumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data.

Results

The highest ⁹⁰Y absorbed dose was observed in liver (3.2 ± 1.8 mGy/MBq) and spleen (2.9 ± 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 ± 0.04 mGy/MBq, and the effective dose was 0.87 ± 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on ⁸⁹Zr-ibritumomab tiuxetan images was high (Pearson correlation coefficient r = 0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower ( r = 0.75).

Conclusion

Biodistribution of ⁸⁹Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with ⁹⁰Y-ibritumomab tiuxetan, and ⁸⁹Zr-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using ¹¹¹In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.