Abstract | UNLABELLED: METHODS: In vivo biodistribution and PET studies were performed in HER1-expressing LS-174T and HER1-negative A375 tumor xenografts. Additionally, studies were performed in different models of intraperitoneal and pulmonary metastases. MRI studies were performed for metastatic models to characterize the targeting potential of (89)Zr-panitumumab at different lesion sites. RESULTS: HER1-mediated targeting was achieved in all HER1-expressing models. The LS-174T tumor area under the curve (AUC) was 3.7-fold greater than the AUC for A375. The LS-174T tumor AUC of 204.13 ± 9.67 was significantly greater (P < 0.001) than the LS-174T tumor AUC of 36.45 ± 1.39 obtained from mice coinjected with 0.1 mg of panitumumab for blocking the target. Differences were observed in 2 intraperitoneal models; tumor uptake in mice with a 3-d tumor burden was more than 2-fold greater than the mice with a 7-d tumor burden. PET and MRI studies revealed HER1-mediated tumor targeting in all metastatic models. However, significant differences were observed between different LS-174T tumor models. Peak tumor uptake of approximately 40 percentage injected dose per gram (%ID/g) was observed at 3-4 d after injection for the subcutaneous tumor model, in contrast to approximately 75 %ID/g at 2 d after injection for the thoracic tumors and approximately 95 %ID/g at 1-2 d after injection for the intraperitoneal tumors. CONCLUSION: The potential utility of (89)Zr-panitumumab in assessing HER1 status in distant metastases and understanding the variations in antibody uptake at different lesion sites is demonstrated in this study. (89)Zr-panitumumab can play a vital role in patient stratification and immunotherapy and therefore warrants further investigation for clinical translation.
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Authors | Tapan K Nayak, Kayhan Garmestani, Diane E Milenic, Martin W Brechbiel |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 53
Issue 1
Pg. 113-20
(Jan 2012)
ISSN: 1535-5667 [Electronic] United States |
PMID | 22213822
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- Radioisotopes
- Panitumumab
- Zirconium
- EGFR protein, human
- ErbB Receptors
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Topics |
- Animals
- Antibodies, Monoclonal
(chemistry, metabolism)
- Cell Line, Tumor
- Cell Transformation, Neoplastic
- Colorectal Neoplasms
(pathology)
- Diagnostic Imaging
(methods)
- ErbB Receptors
(metabolism)
- Female
- Humans
- Lung Neoplasms
(diagnosis, metabolism, secondary)
- Magnetic Resonance Imaging
- Mice
- Panitumumab
- Peritoneal Neoplasms
(diagnosis, metabolism, secondary)
- Positron-Emission Tomography
- Protein Transport
- Radiochemistry
- Radioisotopes
- Risk Assessment
- Zirconium
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