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.
OBJECTIVE
Positron emission tomography (PET) with (89)Zr-ibritumomab tiuxetan can be used to monitor biodistribution of (90)Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of (90)Y-ibritumomab tiuxetan in humans on the basis of (89)Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of (90)Y-ibritumomab tiuxetan influences biodistribution of (89)Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with (89)Zr-ibritumomab tiuxetan can be used to predict biodistribution of (90)Y-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 (89)Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg (90)Y-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 (90)Y 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 (89)Zr-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).


CONCLUSIONS
Biodistribution of (89)Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with (90)Y-ibritumomab tiuxetan, and (89)Zr-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 (111)In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.
Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands. snf.rizvi@vumc.nl
Saiyada N F
SN
Rizvi
Otto J
OJ
Visser
Maria J W D
MJ
Vosjan
Arthur
A
van Lingen
Otto S
OS
Hoekstra
Josée M
JM
Zijlstra
Peter C
PC
Huijgens
Guus A M S
GA
van Dongen
Mark
M
Lubberink
D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D011874:Radiometry; D012008:Recurrence; D033581:Stem Cell Transplantation; D014018:Tissue Distribution; D015040:Zirconium / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; C422802:ibritumomab tiuxetan; D015040:Zirconium