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Quantitative 89Zr Immuno-PET for In Vivo Scouting of 90Y-Labeled Monoclonal Antibodies in Xenograft-Bearing Nude Mice

Iris Verel, MS1, Gerard W.M. Visser, PhD2, Ronald Boellaard, PhD3, Otto C. Boerman, PhD4, Julliette van Eerd, BS4, Gordon B. Snow, MD, PhD1, Adriaan A. Lammertsma, PhD3 and Guus A.M.S van Dongen, PhD1

1 Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
2 Radionuclide Center, VU University, Amsterdam, The Netherlands
3 PET Center, VU University Medical Center, Amsterdam, The Netherlands
4 Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands



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FIGURE 1. Simplified 89Zr decay scheme (modified from ICRP publication (9)). Only transitions in excess of 0.1% abundance are shown. EC = electron capture; IT = isomeric transition; t1/2 = half-life.

 


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FIGURE 2. Biodistribution of coinjected cmAb U36-N-sucDf-89Zr (0.37 MBq, white bars) and cmAb U36-p-BSCN-Bz-DOTA-88Y (0.13 MBq, black bars) in HNX-OE xenograft-bearing mice at 3 h (A), 24 h (B), 48 h (C), 72 h (D), and 144 h (E) after injection. At the indicated time points, 4 mice were bled, sacrificed, and dissected, and radioactivity levels (%ID/g ± SE) of blood, tumor, organs, and gastrointestinal contents were assessed. BL = blood; TU = tumor; SM = sternum; HE = heart; LU = lung; LI = liver; SP = spleen; KI = kidney; MU = muscle; TB = thighbone; CO = colon; CC = colon content; IL = ileum; IC = ileum content; ST = stomach; SC = stomach content.

 


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FIGURE 3. 89Zr-counting-rate linearity determination with HRRT PET camera. Plot is of PET-assessed radioactivity in cylinder phantom versus radioactivity based on dose calibrator measurements. Note presence of linearity, except for highest radioactivity measurement.

 


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FIGURE 4. Spatial resolution determination for 89Zr (dotted line) with HRRT PET camera. Line profile was drawn through image of line source containing 89Zr. For comparison, line profile for 18F (solid line) is also shown.

 


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FIGURE 5. HSRCs (A) and sphere size estimations (B) for 89Zr ({circ}) with HRRT PET camera. For comparison, 18F ({blacksquare}) data are also shown. For this purpose, 50% isocontour ROIs were drawn around spheres of Jaszczak phantom.

 


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FIGURE 6. HRRT PET images of HNX-OE xenograft-bearing mouse injected with cmAb U36-N-sucDf-89Zr (3.7 MBq) at 72 h after injection. Coronal image plane (A) in which both tumors (left, 124 mg; right, 26 mg) were visible was chosen. Transaxial image planes in which right tumor was optimally visible (B, top) or left tumor was optimally visible (B, middle and bottom) were chosen. Bottom panel of B illustrates approach to arrive at ring-shaped area used for surroundings determination.

 


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FIGURE 7. Correlation between PET-assessed tumor uptake and ex vivo-assessed tumor uptake. HNX-OE xenograft-bearing mice were injected with cmAb U36-N-sucDf-89Zr (3.7 MBq) and scanned at 1 d ({diamond}, n = 2), 2 d ({triangleup}, n = 2), or 3 d ({diamondsuit}, n = 8) with HRRT PET camera. Immediately after being scanned, mice were dissected and radioactivity levels in tumors were determined with {gamma}-counter. After reconstruction of images, VOIs were drawn over tumors and radioactivity amounts were calculated. (A) After correction for partial-volume effects, PET-assessed (image-derived) tumor radioactivity values were plotted as function of ex vivo-assessed ({gamma}-counter-derived) tumor radioactivity values. Ratio of ex vivo-assessed and PET-assessed tumor radioactivity values, corrected (B) or not corrected (C) for partial-volume effects, was plotted as function of VOI.

 





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