| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Internal Medicine, University of California Davis Medical Center, Sacramento
Department of Chemistry, University of California, Davis, Sacramento, California
Brookhaven National Laboratory, Upton, New York
Correspondence: For correspondence or reprints contact: Sally J. DeNardo, MD, Section of Radiodiagnosis/Therapy, Molecular Cancer Institute, 1508 Alhambra Blvd., #3100, Sacramento, CA 95816.
ABSTRACT
Iym-1, a monoclonal antibody that preferentially targets malignant lymphocytes has induced therapeutic responses and prolonged survival in patients with non-Hodgkin's lymphoma when labeled with 131I. Radiometal-labeled antibodies provide higher tumor radiation doses than corresponding 131I antibodies. 67Cu has an exceptional combination of properties desirable for radioimmunotherapy, including gamma and beta emissions for imaging and therapy, respectively, a biocompatible half-time and absence of pathways contributing to myelotoxicity. The radioimmunoconjugate, 67Cu-2IT-BAT-Lym-1, has been shown to be efficacious in nude mice bearing human Burkitt's lymphoma (Raji) xenografts. Based on these results, a clinical study of the pharmacokinetics and dosimetry of 67Cu-2IT-BAT-Lym-1 in patients with lymphoma was initiated. Methods: Eleven patients with advanced stage 3 or 4 lymphoma were given a preload dose of unmodified Lym-1, then an imaging dose of 126–533 MBq (3.4–14.4 mCi) 67Cu-2IT-BAT-Lym-1. Total Lym-1 ranged from 25 to 70 mg dependent on the specific activity of the radioimmunoconjugate and was infused at a rate of 0.5–1 mg/min. Imaging, physical examination, including caliper measurement of superficial tumors, and analysis of blood, urine and fecal samples were performed for a period of 6–13 d after infusion to assess pharmacokinetics, radiation dosimetry, toxicity and tumor regression. Results: In 7 patients, in whom superficial tumors had been accurately measured, tumors regressed from 18% to 75% (mean 48%) within several days of 67Cu-2IT-BAT-Lym-1 infusion. The uptake and biological half-time of 67Cu-2IT-BAT-Lym-1 in tumors were greater than those of normal tissues, except the mean liver half-time exceeded the mean tumor half-time. The mean tumor-to-marrow radiation ratio was 32:1, tumor-to-total body was 24:1 and tumor-to-liver was 1.5:1. Images were of very good quality; tumors and normal organs were readily identified. Mild and transient Lym-1 toxicity occurred in 6 patients; 1 patient developed a human antimouse antibody. There were no significant changes in blood counts or serum chemistries indicative of radiation toxicity. Conclusion: Because of the long residence time of 67Cu-2IT-BAT-Lym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tumor regressions were observed after imaging doses. The results indicate considerable therapeutic potential for 67Cu-2IT-BAT-Lym-1.
Key Words: radioimmunotherapy • 67Cu • lymphoma • pharmacokinetics • radiation dosimetry
This article has been cited by other articles:
|
|
 |
|
  S. J. DeNardo, G. L. DeNardo, A. Natarajan, L. A. Miers, A. R. Foreman, C. Gruettner, G. N. Adamson, and R. Ivkov Thermal Dosimetry Predictive of Efficacy of 111In-ChL6 Nanoparticle AMF-Induced Thermoablative Therapy for Human Breast Cancer in Mice J. Nucl. Med., March 1, 2007; 48(3): 437 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. DeNardo, G. L. DeNardo, L. A. Miers, A. Natarajan, A. R. Foreman, C. Gruettner, G. N. Adamson, and R. Ivkov Development of Tumor Targeting Bioprobes (111In-Chimeric L6 Monoclonal Antibody Nanoparticles) for Alternating Magnetic Field Cancer Therapy Clin. Cancer Res., October 1, 2005; 11(19): 7087s - 7092s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Grunberg, I. Novak-Hofer, M. Honer, K. Zimmermann, K. Knogler, P. Blauenstein, S. Ametamey, H. R. Maecke, and P. A. Schubiger In vivo Evaluation of 177Lu- and 67/64Cu-Labeled Recombinant Fragments of Antibody chCE7 for Radioimmunotherapy and PET Imaging of L1-CAM-Positive Tumors Clin. Cancer Res., July 15, 2005; 11(14): 5112 - 5120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Tuscano, R. T. O'Donnell, L. A. Miers, L. A. Kroger, D. L. Kukis, K. R. Lamborn, T. F. Tedder, and G. L. DeNardo Anti-CD22 ligand-blocking antibody HB22.7 has independent lymphomacidal properties and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma xenografts Blood, May 1, 2003; 101(9): 3641 - 3647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Witzig, C. A. White, L. I. Gordon, G. A. Wiseman, C. Emmanouilides, J. L. Murray, J. Lister, and P. S. Multani Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin's Lymphoma J. Clin. Oncol., April 1, 2003; 21(7): 1263 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Buchsbaum and A. F. LoBuglio Targeting of 125I-Labeled B Lymphocyte Stimulator J. Nucl. Med., March 1, 2003; 44(3): 434 - 436. [Full Text] [PDF]
|
|
|
|
|
|
R. T. O'Donnell, S. J. DeNardo, A. Yuan, S. Shen, C. M. Richman, P. N. Lara, I. J. Griffith, D. S. Goldstein, D. L. Kukis, G. S. Martinez, et al. Radioimmunotherapy with 111In/90Y-2IT-BAD-m170 for Metastatic Prostate Cancer Clin. Cancer Res., June 1, 2001; 7(6): 1561 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goel, S. Augustine, J. Baranowska-Kortylewicz, D. Colcher, B. J. M. Booth, G. Pavlinkova, M. Tempero, and S. K. Batra Single-Dose versus Fractionated Radioimmunotherapy of Human Colon Carcinoma Xenografts Using 131I-labeled Multivalent CC49 Single-chain Fvs Clin. Cancer Res., January 1, 2001; 7(1): 175 - 184. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY | THE JOURNAL OF NUCLEAR MEDICINE |
