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Meeting ReportOncology - Basic: Basic Science

PET radioimmunodetection of neuroblastoma: Optimizing pharmacokinetics through antibody engineering

Jason Dearling, Stephan Voss, Patricia Dunning, Erin Snay, Frederick Fahey, Ted Treves and Alan Packard
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1556;
Jason Dearling
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Stephan Voss
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Patricia Dunning
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Erin Snay
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Frederick Fahey
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Ted Treves
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Alan Packard
1Division of Nuclear Medicine, Department of Radiology, Childrens Hospital Boston and Harvard Medical School, Boston, MA
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Abstract

1556

Objectives To identify the optimal antibody format for PET detection of neuroblastoma.

Methods Whole IgG ch14.18 (150 kDa) and its ΔCH2 (120 kDa) and scFv-Fc (100 kDa) derivatives were conjugated to pba-DOTA and labeled with 64Cu. The labeled radioimmunoconjugate (RIC) (50 μg, 100-250 μCi each) was injected into mice bearing M21 tumors. MicroPET images were collected at 1, 24 and 48 hours post-injection, followed by a biodistribution study.

Results MicroPET imaging and the biodistribution study demonstrated that these bivalent RICs localized to the tumor. Blood clearance for the smaller molecules was more rapid: ch14.18 (n = 5) 5.9 ±1.4 %ID/g; ΔCH2 (n = 3) 1.5 ±0.3 %ID/g; scFv-Fc (n = 5) 3.9 ±0.8 %ID/g (Ab and scFv-Fc vs ΔCH2 P < 0.05, Ab vs scFv-Fc P > 0.05). The normal tissue distribution of the molecules also varied. Liver uptake for the intact antibody was 7.4 ±3.0 %ID/g, but for ΔCH2: 12.9 ±1.9 %ID/g; and scFv-Fc 9.9 ±0.8 %ID/g. Kidney uptake followed a different pattern, with low intact antibody and ΔCH2 uptake (3.7 ±1.2 %ID/g and 3.7 ±0.4 %ID/g respectively) but higher scFv-Fc uptake (7.6 ±1.2 %ID/g, all data 48 hours p.i.).

Conclusions Blood levels of the whole antibody and scFv-Fc molecules were probably maintained through recycling by the FcRn molecule binding to intact Fc regions. More rapid clearance from non-target tissues, reducing exposure to the radionuclide, suggests that the Cu-64-labeled ▵CH2 molecule would be a better format for clinical detection of neuroblastoma lesions.

Research Support National Institutes of Health Grants 5K08CA093554 and 5R01CA094338.

  • © 2009 by Society of Nuclear Medicine
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Journal of Nuclear Medicine
Vol. 50, Issue supplement 2
May 2009
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PET radioimmunodetection of neuroblastoma: Optimizing pharmacokinetics through antibody engineering
Jason Dearling, Stephan Voss, Patricia Dunning, Erin Snay, Frederick Fahey, Ted Treves, Alan Packard
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1556;

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PET radioimmunodetection of neuroblastoma: Optimizing pharmacokinetics through antibody engineering
Jason Dearling, Stephan Voss, Patricia Dunning, Erin Snay, Frederick Fahey, Ted Treves, Alan Packard
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1556;
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