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J Nucl Med. 2008; 49 (Supplement 1):320P
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Oncology-Basic Science: Basic Science

Basic Science Posters

PET detection of neuroblastoma: Comparison of the in vivo distribution of 64Cu-labeled IgG ch14.18 and its CH2-deleted derivative ch14.18-deltaCH2

Jason Dearling1, S. Voss1, P. Dunning1, E. Snay1, F. Fahey1, S. Treves1 and A. Packard1

1 Division of Nuclear Medicine and Department of Radiology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts

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Objectives: The following hypothesis was tested: Copper-64-labeled ch14.18-deltaCH2 (MW 120 kDa) has improved imaging properties compared with its parent IgG (ch14.18, MW 150 kDa).

Methods: The two antibodies were conjugated to parabenzylamino DOTA using EDC, labeled with 64Cu, and purified by semi-preparative HPLC. Radiopharmaceutical purity was >95%. Radioimmunoconjugate (50 µg, 100-250 µCi each) was injected into nude mice bearing SC M21 tumors. MicroPET images were collected at 1, 24 and 48 hours post-injection, and a biodistribution study was carried out at 48 hours post-injection.

Results: The microPET imaging and subsequent biodistribution study demonstrated that both radioimmunoconjugates localized to tumor: ch14.18 = 11.4 ± 7.1 %ID/g; ch14.18-deltaCH2 = 4.57 ± 1.9 %ID/g (all data at 48 h p.i.). Normal tissue uptake for the whole antibody was significantly higher than for the smaller deltaCH2 derivative in most tissues, and similar in liver (ch14.18 = 6.32 ± 0.89 %ID/g; ch14.18-deltaCH2 = 7.12 ± 0.62 %ID/g; P = 0.92) and gut (ch14.18 = 2.67 ± 0.38 %ID/g; ch14.18-deltaCH2 = 1.47 ± 0.49 %ID/g; P = 0.056). Blood clearance of radiolabeled ch14.18-deltaCH2 was much faster than that of the parent antibody (ch14.18 = 9.76 ± 0.89 %ID/g, ch14.18-deltaCH2 = 0.628 ± 0.19 %ID/g).

Conclusions: The [64Cu]-pbaDOTA-ch14.18-deltaCH2 molecule demonstrated improved biodistribution properties (faster blood clearance, lower uptake in normal tissues) compared with the radiolabeled parent antibody, suggesting that it would be a better tool in clinical detection of neuroblastoma lesions.

Research Support: This work was supported by National Institutes of Health Grants 5K08CA093554 and 5R01CA094338.





This Article
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Right arrow Articles by Packard, A.