Impact of rituximab treatment on (90)Y-ibritumomab dosimetry for patients with non-Hodgkin lymphoma.
To determine whether the therapeutic effect of (90)Y-ibritumomab might be enhanced by a full course of rituximab followed by single dose of (90)Y-ibritumomab, the trial included pre- and post-rituximab treatment imaging with (111)In-ibritumomab and blood pharmacokinetics. Comparison of the pre- and post-rituximab imaging and blood data allowed for the assessment of impact of rituximab on (90)Y-ibritumomab dosimetry.


METHODS
Seventeen patients with relapsed B cell non-Hodgkin lymphoma first received 250 mg/m(2) of rituximab plus 185 MBq of (111)In-ibritumomab for initial dosimetry evaluation. In weeks 2-4, patients received 3 weekly 375 mg/m(2) doses of rituximab. In week 6, patients received a 250 mg/m(2) dose of rituximab plus 185 MBq of (111)In-ibritumomab for a second dosimetry evaluation. Five sequential, whole-body gamma-camera images were acquired after the (111)In-ibritumomab injection. Calculated radiation doses were based on patient-specific organ masses. For each patient, paired comparison of radiation doses before and after rituximab treatment was performed. Paired comparison of residence times for spleen and tumor was also performed.


RESULTS
Before rituximab treatment, the median radiation dose (mGy/MBq) was 0.48 (range, 0.24-0.86) for total body, 3.7 (range, 2.1-11.6) for liver, 6.1 (range, 1.8-17.8) for spleen, 3.3 (range, 2.0-4.7) for kidneys, 2.4 (range, 1.3-3.7) for heart wall, 1.1 (range, 0.4-2.3) for lungs, 0.79 (range, 0.32-1.22) for marrow from blood, and 18.1 (range, 4.7-98.9) for tumor. Paired comparisons were performed in 16 patients only because human antimurine antibody developed in 1 patient. The median change was 0.007 mGy/MBq for body, -0.14 mGy/MBq for liver, -0.31 mGy/MBq for kidneys, 0.38 mGy/MBq for heart wall, -0.17 mGy/MBq for lungs, and 0.046 mGy/MBq for marrow from blood. The median change in residence time was -0.92 h for spleen and -0.24 h for tumor. The changes were statistically insignificant for total body, liver, kidneys, lungs, and marrow from blood. The median residence times, or mGy/MBq if there were no volume changes, decreased 24% for spleen (P = 0.0005) and 28% for tumor (P = 0.005). The median radiation dose to heart wall increased 16%, which was statistically significant (P = 0.002).


CONCLUSIONS
Changes in (90)Y-ibritumomab dosimetry after 4 wk of rituximab treatment were not significant for most organs, except for the heart wall. The reduction of spleen and tumor residence times is more likely to be due to the therapeutic effects of rituximab.
Shen
Sui
S
Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. sshen@uabmc.edu
Forero
Andres
A
Meredith
Ruby F
RF
Shah
Jatin J
JJ
Knox
Susan J
SJ
Wiseman
Gregory A
GA
Usrey
Marc E
ME
Lobuglio
Albert F
AF
D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging / Q000628:therapy*; D009929:Organ Size / Q000502:physiology; D049268:Positron-Emission Tomography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069283:Rituximab; D014057:Tomography, X-Ray Computed; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan