| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Basic Science Investigations |
1 Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
2 Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
3 NeoRx Corp., Seattle, Washington
4 Pacific Northwest National Laboratory, Richland, Washington
5 Biostatistics Division, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)4 and streptavidin, in conjunction with 90Y/111In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted 90Y/111In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. Methods: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m2 of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) 90Y/111In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body 111In images were acquired immediately and at 2–144 h after injection of 90Y/111In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor 90Y doses were calculated based on 111In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. Results: The 90Y/111In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean 90Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32–0.78) to whole body, 3.75 (0.63–6.89) to liver, 2.32 (0.58–4.46) to spleen, 7.02 (3.36–11.2) to kidneys, 0.30 (0.09–0.44) to lungs, 0.22 (0.12–0.34) to marrow, and 28.9 (4.18–121.6) to tumors. Conclusion: Radiation dose to normal organs from circulating radionuclide is substantially reduced using pretargeted RIT. Tumor-to-normal organ dose ratios were increased about 8- to 11-fold compared with reported patient-specific mean dose to liver, spleen, marrow, and tumors from 90Y-CC49.
Key Words: gastrointestinal cancer • dosimetry • pretargeted radioimmunotherapy
Related articles in JNM:
This article has been cited by other articles:
|
|
 |
|
  F. Buchegger, O. W. Press, A. B. Delaloye, and N. Ketterer Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma Oncologist, June 1, 2008; 13(6): 657 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Meredith, S. Shen, A. Forero, and A. LoBuglio A Method to Correct for Radioactivity in Large Vessels That Overlap the Spine in Imaging-Based Marrow Dosimetry of Lumbar Vertebrae J. Nucl. Med., February 1, 2008; 49(2): 279 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Y. Brard, H. Karacay, R. Stein, R. M. Sharkey, M. J. Mattes, C.-H. Chang, E. A. Rossi, W. J. McBride, and D. M. Goldenberg A Divalent Hapten-Peptide Induces Apoptosis in Human Non Hodgkin Lymphoma Cell Lines Targeted by Anti-CD20 x Anti-Hapten Bispecific Antibodies Clin. Cancer Res., September 15, 2007; 13(18): 5564s - 5571s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pantelias, J. M. Pagel, N. Hedin, L. Saganic, S. Wilbur, D. K. Hamlin, D. S. Wilbur, Y. Lin, D. Stone, D. Axworthy, et al. Comparative biodistributions of pretargeted radioimmunoconjugates targeting CD20, CD22, and DR molecules on human B-cell lymphomas Blood, June 1, 2007; 109(11): 4980 - 4987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Mamelak, S. Rosenfeld, R. Bucholz, A. Raubitschek, L. B. Nabors, J. B. Fiveash, S. Shen, M.B. Khazaeli, D. Colcher, A. Liu, et al. Phase I Single-Dose Study of Intracavitary-Administered Iodine-131-TM-601 in Adults With Recurrent High-Grade Glioma J. Clin. Oncol., August 1, 2006; 24(22): 3644 - 3650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Pagel, Y. Lin, N. Hedin, A. Pantelias, D. Axworthy, D. Stone, D. K. Hamlin, D. S. Wilbur, and O. W. Press Comparison of a tetravalent single-chain antibody-streptavidin fusion protein and an antibody-streptavidin chemical conjugate for pretargeted anti-CD20 radioimmunotherapy of B-cell lymphomas Blood, July 1, 2006; 108(1): 328 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Goldenberg, R. M. Sharkey, G. Paganelli, J. Barbet, and J.-F. Chatal Antibody Pretargeting Advances Cancer Radioimmunodetection and Radioimmunotherapy J. Clin. Oncol., February 10, 2006; 24(5): 823 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Forster, E. B. Santos, P. M. Smith-Jones, P. Zanzonico, and S. M. Larson Pretargeted Radioimmunotherapy with a Single-Chain Antibody/Streptavidin Construct and Radiolabeled DOTA-Biotin: Strategies for Reduction of the Renal Dose J. Nucl. Med., January 1, 2006; 47(1): 140 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Karacay, P.-Y. Brard, R. M. Sharkey, C.-H. Chang, E. A. Rossi, W. J. McBride, D. R. Ragland, I. D. Horak, and D. M. Goldenberg Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft Clin. Cancer Res., November 1, 2005; 11(21): 7879 - 7885. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY | THE JOURNAL OF NUCLEAR MEDICINE |
