| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | RSS | TABLE OF CONTENTS |
|
|
|
||||||||
|
||||||||||
Departments of Otolaryngology/Head and Neck Surgery, Nuclear Medicine, Clinical Chemistry, and Hematology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
A phase I therapy study was conducted to determine the safety, maximum tolerated dose (MTD), pharmacokinetics, dosimetry, immunogenicity, and therapeutic potential of 186Re-labeled anti-CD44v6 chimeric monoclonal antibody (cMAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC). The potential of a diagnostic study with 99mTc-cMAb U36 to predict the biodistribution of 186Re-cMAb U36 was evaluated. Methods: Thirteen patients with recurrent or metastatic HNSCC were given 750 MBq 99mTc-cMAb U36 (2 mg) followed 1 wk later by a single dose of 186Re-cMAb U36 (12 or 52 mg) in radiation dose-escalating steps of 0.4, 1.0, and 1.5 GBq/m2. After each administration, planar and SPECT images were obtained, and the pharmacokinetics and development of human antimurine as well as anti-cMAb responses were determined. Radiation absorbed doses to tumor, red marrow, and organs were calculated. Results: Administration was well tolerated, and excellent targeting of tumor lesions was seen in all patients. Dose-limiting myelotoxicity (thrombocytopenia being most prominent) was the only toxicity observed, resulting in grade 4 myelotoxicity in 2 patients treated with 1.5 GBq/m2. The MTD was established at 1.0 GBq/m2, at which a transient grade 3 thrombocytopenia was seen in 1 patient. One patient showed stable disease for 6 mo after treatment at the MTD. The 2 patients with dose-limiting myelotoxicity showed a marked reduction in tumor size. The reduction was of short duration and, therefore, not considered an objective response. Tumor absorbed doses at MTD ranged from 3.0 to 18.1 Gy. Red marrow doses ranged from 20 to 112 cGy (mean, 51 ± 16 cGy/GBq) and correlated with platelet nadir (r = 0.8; P < 0.01). Pharmacokinetics varied between patients treated at the same dose level and were accurately predicted by the diagnostic procedure. Five patients experienced a human anti-cMAb response, 1 of which was a human antimouse antibody response. Conclusion: This study shows that 186Re-cMAb U36 can be safely administered, with dose-limiting myelotoxicity at 41 mCi/m2. The use of cMAb U36 instead of its murine counterpart did not decrease the induction of human antibody responses. The availability of a 99mTc-labeled diagnostic study that can predict the pharmacokinetics of 186Re-cMAb U36 offers the possibility of using such a study for selection of a safe radioimmunotherapy dose.
Key Words: radioimmunotherapy • monoclonal antibodies • 186Re • dosimetry • pharmacokinetics • head and neck cancer
Received Dec. 14, 1999; revision accepted May 5, 2000.
For correspondence or reprints contact: Guus A.M.S. van Dongen, PhD, Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Related articles in JNM:
This article has been cited by other articles:
|
|
 |
|
  P. K.E. Borjesson, Y. W.S. Jauw, R. de Bree, J. C. Roos, J. A. Castelijns, C. R. Leemans, G. A.M.S. van Dongen, and R. Boellaard Radiation Dosimetry of 89Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients J. Nucl. Med., November 1, 2009; 50(11): 1828 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A.M.S. van Dongen, G. W.M. Visser, M. N. Lub-de Hooge, E. G. de Vries, and L. R. Perk Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications Oncologist, December 1, 2007; 12(12): 1379 - 1389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Tijink, J. Buter, R. de Bree, G. Giaccone, M. S. Lang, A. Staab, C. R. Leemans, and G. A.M.S. van Dongen A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus. Clin. Cancer Res., October 15, 2006; 12(20): 6064 - 6072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Tijink, D. Neri, C. R. Leemans, M. Budde, L. M. Dinkelborg, M. Stigter-van Walsum, L. Zardi, and G. A.M.S. van Dongen Radioimmunotherapy of Head and Neck Cancer Xenografts Using 131I-Labeled Antibody L19-SIP for Selective Targeting of Tumor Vasculature J. Nucl. Med., July 1, 2006; 47(7): 1127 - 1135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Zalutsky Potential of immuno-positron emission tomography for tumor imaging and immunotherapy planning. Clin. Cancer Res., April 1, 2006; 12(7): 1958 - 1960. [Full Text] [PDF]
|
|
|
|
|
|
P. K.E. Borjesson, Y. W.S. Jauw, R. Boellaard, R. de Bree, E. F.I. Comans, J. C. Roos, J. A. Castelijns, M. J.W.D. Vosjan, J. A. Kummer, C. R. Leemans, et al. Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody u36 in the detection of lymph node metastases in head and neck cancer patients. Clin. Cancer Res., April 1, 2006; 12(7): 2133 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Brouwers, W. C.A.M. Buijs, P. F.A. Mulders, P. H.M. de Mulder, W. J.M. van den Broek, C. Mala, E. Oosterwijk, O. C. Boerman, F. H.M. Corstens, and W. J.G. Oyen Radioimmunotherapy with [131I]cG250 in Patients with Metastasized Renal Cell Cancer: Dosimetric Analysis and Immunologic Response Clin. Cancer Res., October 1, 2005; 11(19): 7178s - 7186s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Postema, P. K.E. Borjesson, W. C.A.M. Buijs, J. C. Roos, H. A.M. Marres, O. C. Boerman, R. de Bree, M. Lang, G. Munzert, G. A.M.S. van Dongen, et al. Dosimetric Analysis of Radioimmunotherapy with 186Re-Labeled Bivatuzumab in Patients with Head and Neck Cancer J. Nucl. Med., October 1, 2003; 44(10): 1690 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. E. Borjesson, E. J. Postema, J. C. Roos, D. R. Colnot, H. A. M. Marres, M. H. van Schie, G. Stehle, R. de Bree, G. B. Snow, W. J. G. Oyen, et al. Phase I Therapy Study with 186Re-labeled Humanized Monoclonal Antibody BIWA 4 (Bivatuzumab) in Patients with Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., September 1, 2003; 9(10): 3961s - 3972s. [Abstract] [Full Text]
|
|
|
|
|
|
I. Verel, G. W.M. Visser, R. Boellaard, M. Stigter-van Walsum, G. B. Snow, and G. A.M.S van Dongen 89Zr Immuno-PET: Comprehensive Procedures for the Production of 89Zr-Labeled Monoclonal Antibodies J. Nucl. Med., August 1, 2003; 44(8): 1271 - 1281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Colnot, G. J. Ossenkoppele, J. C. Roos, J. J. Quak, R. de Bree, P. K. Borjesson, P. C. Huijgens, G. B. Snow, and G. A. M. S. van Dongen Reinfusion of Unprocessed, Granulocyte Colony-stimulating Factor-stimulated Whole Blood Allows Dose Escalation of 186Relabeled Chimeric Monoclonal Antibody U36 Radioimmunotherapy in a Phase I Dose Escalation Study Clin. Cancer Res., November 1, 2002; 8(11): 3401 - 3406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Colnot, A. J. Wilhelm, J. Cloos, J. C. Roos, R. de Bree, J. J. Quak, G. B. Snow, and G. A.M.S. van Dongen Evaluation of Limited Blood Sampling in a Preceding 99mTc-Labeled Diagnostic Study to Predict the Pharmacokinetics and Myelotoxicity of 186Re-cMAb U36 Radioimmunotherapy J. Nucl. Med., September 1, 2001; 42(9): 1364 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. B. Breitz How Far Have We Come with Solid (Nonhematologic) Tumor Radioimmunotherapy? J. Nucl. Med., December 1, 2000; 41(12): 2011 - 2014. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | RSS | TABLE OF CONTENTS |
| JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY | THE JOURNAL OF NUCLEAR MEDICINE |
