Page 31 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
P. 31
Dosimetry of immuno-PET with 89Zr-cmAb U36
RESULTS
Unless otherwise specified, all 89Zr activities are decay corrected to time of
injection. For 1 patient (patient 18) imaged, not enough data were available for 2 adequate dosimetric analysis. Regarding the evaluation of 89Zr-immuno-PET
imaging to quantify tumor uptake, 4 patients (patients 1, 2, 13, and 18) were
excluded from analysis because the lack of a scan at 144 h p.i. Another patient
(patient 6) was excluded because of delayed surgery 2 wk p.i.
Safety
89Zr-cmAbU36 was found to be safe and well tolerated in all subjects. Neither adverse reactions nor significant changes in earlier mentioned blood and urine parameters were observed, that could be related to the study drug. The mean radiation dose rates measured 1, 24, and 72 h p.i. at a distance of 100 cm were 7.0 ± 0.3, 5.7 ± 0.3 and 3.8 ± 0.2 μSv/h, respectively. Patient 9 and 10 developed a human anti-chimeric antibody (HACA) response, and elevated titers were found at 1 and 6 wk p.i., irrespective whether cmAb U36 IgG or 89Zr-N-sucDf-cmAb U36 was used in the ELISA. These data indicate that the response was directed to the protein part of the conjugate and not to the N-sucDf chelate attached to the cmAb.
Biodistribution
Images of a representative male patient between 1 and 144 h after injection of 89Zr- cmAbU36 are presented in Figure 1. Whole body images obtained directly after administration of 89Zr-cmAb U36 showed mainly blood-pool activity with delineation of the heart, lungs, liver, kidneys, spleen and nose. Uptake of radioactivity for most organs decreased over time, while increased uptake was only seen at tumor sites and in the thyroid of some of the patients (patients 1, 6, 7, 10, and 11).
The estimated uptake of 89Zr-cmAbU36 in single organs, is presented in Table 2. The visual quality of the immuno-PET images varied between different patients. Figure 2 illustrates the difference in visual quality between an average weight patient (58 kg) and an obese patient (104 kg).
29
