(124)I-huA33 antibody uptake is driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET Journal Article

Authors: O'Donoghue, J. A.; Smith-Jones, P. M.; Humm, J. L.; Ruan, S.; Pryma, D. A.; Jungbluth, A. A.; Divgi, C. R.; Carrasquillo, J. A.; Pandit-Taskar, N.; Fong, Y.; Strong, V. E.; Kemeny, N. E.; Old, L. J.; Larson, S. M.
Article Title: (124)I-huA33 antibody uptake is driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET
Abstract: The primary aim of this analysis was to examine the quantitative features of antibody-antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients. Methods: Humanized anti-A33 antibody (10 mg) labeled with the positron-emitting radionuclide 124I (124IhuA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination. Results: PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of 124I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ∼0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ∼0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%-50%. Conclusion: The in vivo biodistribution of 124I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (α- or β-particle) emissions. Copyright © 2011 by the Society of Nuclear Medicine, Inc.
Keywords: colorectal cancer; radioimmunotherapy; 124i; immuno-pet; hua33
Journal Title: Journal of Nuclear Medicine
Volume: 52
Issue: 12
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2011-12-01
Start Page: 1878
End Page: 1885
Language: English
DOI: 10.2967/jnumed.111.095596
PROVIDER: scopus
PUBMED: 22068895
PMCID: PMC3394180
Notes: --- - "Export Date: 1 February 2012" - "CODEN: JNMEA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Daniel Alexander Pryma
    7 Pryma
  2. Chaitanya Divgi
    160 Divgi
  3. Yuman Fong
    772 Fong
  4. Vivian Strong
    169 Strong
  5. John Laurence Humm
    366 Humm
  6. Achim Jungbluth
    387 Jungbluth
  7. Shutian Ruan
    50 Ruan
  8. Steven M Larson
    878 Larson
  9. Lloyd J Old
    436 Old
  10. Nancy Kemeny
    437 Kemeny