HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reilly, R. M. Articles by Vallis, K. A. Search for Related Content PubMed PubMed Citation Articles by Reilly, R. M. Articles by Vallis, K. A.

Preclinical Pharmacokinetic, Biodistribution, Toxicology, and Dosimetry Studies of ¹¹¹In-DTPA-Human Epidermal Growth Factor: An Auger Electron–Emitting Radiotherapeutic Agent for Epidermal Growth Factor Receptor–Positive Breast Cancer

¹ Division of Nuclear Medicine, University Health Network, Toronto, Ontario, Canada; ² Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada; ³ Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada; ⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; ⁵ Department of Radiation Oncology, The Princess Margaret Hospital, Toronto, Ontario, Canada; ⁶ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; and ⁷ Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Correspondence: For correspondence or reprints contact: Raymond M. Reilly, PhD, Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ontario M5S 2S2, Canada. E-mail: raymond.reilly{at}utoronto.ca

Our objective was to evaluate the pharmacokinetics, normal tissue distribution, radiation dosimetry, and toxicology of human epidermal growth factor (hEGF) labeled with ¹¹¹In (¹¹¹In-diethylenetriaminepentaacetic acid [DTPA]-hEGF) in mice and rabbits. Methods: ¹¹¹In-DTPA-hEGF (3.6 MBq; 1.3 or 13 µg) was administered intravenously to BALB/c mice. The blood concentration–time data were fitted to a 3-compartment model. Acute toxicity was studied with female BALB/c mice at 42 times the maximum planned human dose (MBq/kg) or with New Zealand White rabbits at 1 times the maximum planned human dose (MBq/kg) for a phase I clinical trial. Toxicity was evaluated by monitoring body weight, by determination of hematology and clinical biochemistry parameters, and by morphologic examination of tissues. Radiation dosimetry projections in humans were estimated on the basis of the residence times in mice by use of the OLINDA version 1.0 computer program. Results: The largest amounts of radioactivity were taken up by the liver (41.3 ± 7.8 [mean ± SD] percentage injected dose [%ID] at 1 h after injection and decreasing to 4.9 ± 0.3 %ID at 72 h after injection) and kidneys (18.6 ± 0.8 %ID at 1 h and decreasing to 4.5 ± 0.2 %ID at 72 h after injection). ¹¹¹In-DTPA-hEGF was cleared rapidly from the blood, with a half-life at -phase of 2.7–6.2 min and a half-life at ß-phase of 24.0–36.3 min. The half-life of the long terminal phase could not be accurately determined. The volume of distribution of the central compartment was 340–375 mL/kg, and the volume of distribution at steady state was 430–685 mL/kg. There was no significant difference in the ratio of body weight at 15 d to pretreatment weight for mice administered ¹¹¹In-DTPA-hEGF (1.02 ± 0.01) and mice administered unlabeled DTPA-hEGF (1.01 ± 0.01). Erythrocyte, leukocyte, and platelet counts and serum alanine aminotransferase and creatinine levels remained in the normal ranges. No morphologic changes were observed by light microscopy in any of 19 tissues sampled. Minor morphologic changes in the liver were observed by electron microscopy. The projected whole-body dose in humans was 0.19 mSv·MBq^–1. The projected doses to the liver, kidneys, and lower large intestine were 0.76, 1.82, and 1.12 mSv·MBq^–1, respectively. Conclusion: ¹¹¹In-DTPA-hEGF was safely administered to mice and rabbits at multiples of the maximum dose planned for a phase I trial in breast cancer patients.

Key Words: breast cancer • ¹¹¹In-DTPA-hEGF • pharmacokinetics • toxicology • radiation dosimetry

Related articles in JNM:

This Month in JNM

JNM 2006 47: 11a-12a. [Full Text]  

This article has been cited by other articles:

				G. TING, C.-H. CHANG, and H.-E. WANG Cancer Nanotargeted Radiopharmaceuticals for Tumor Imaging and Therapy Anticancer Res, October 1, 2009; 29(10): 4107 - 4118. [Abstract] [Full Text] [PDF]

				Z. Cai, Z. Chen, K. E. Bailey, D. A. Scollard, R. M. Reilly, and K. A. Vallis Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to 111In-DTPA-hEGF J. Nucl. Med., August 1, 2008; 49(8): 1353 - 1361. [Abstract] [Full Text] [PDF]

				D. A. Mankoff, J. M. Link, H. M. Linden, L. Sundararajan, and K. A. Krohn Tumor Receptor Imaging J. Nucl. Med., June 1, 2008; 49(Suppl_2): 149S - 163S. [Abstract] [Full Text] [PDF]