This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Yang, W. Articles by Caligiuri, M. A. Search for Related Content PubMed PubMed Citation Articles by Yang, W. Articles by Caligiuri, M. A.

Convection-enhanced Delivery of Boronated Epidermal Growth Factor for Molecular Targeting of EGF Receptor-positive Gliomas¹

Department of Pathology [W. Y., R. F. B., D. M. A.], College of Pharmacy [S. S., W. T.], and Department of Internal Medicine [M. A. C.], The James Cancer Hospital and Comprehensive Cancer Center [R. F. B., M. A. C.], The Ohio State University, Columbus, Ohio 43210, and Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York 14263 [M. J. C., R. A. F.]

Convection enhanced delivery (CED) is potentially a powerful method to improvethe targeting of macromolecules to the central nervous system by applying a pressure gradient to establish bulk flow through the brain interstitium during infusion. The purpose of the present study was to evaluate CED as a means to improve the intracerebral and intratumoral (i.t.) uptake of a heavily boronated macromolecule (dendrimer; BD) linked to epidermal growth factor (EGF) for neutron capture therapy in rats bearing a syngeneic epidermal growth factor receptor (EGFR) + glioma. Boronated EGF was radiolabeled with ¹²⁵I and administered by CED at a rate of 0.33 µl/min for 15, 30, and 60 min [infusion volumes (V_I) of 5, 10, and 20 µl, respectively], using a syringe pump connected to an indwelling cannula implanted into the right caudate nucleus of normal rats or i.t. in rats bearing either F98_EGFR or F98 wild-type (F98_WT) gliomas. After infusion, rats were euthanized, and their brains were removed and serially sectioned. The uptake and biodistribution of ¹²⁵I-boronated EGF in tumor or brain was studied by quantitative autoradiography and -scintillation counting. The volume of distribution (V_d) in brain was assessed using a computer interfaced image analysis system. After CED, the V_d increased from 34.4 to 123.5 µl with corresponding V_i ranging from 5 to 20 µl. The V_d of BD-EGF in the brain was 64.8 ± 13.4 µl with CED (V_i 10 µ), and the V_d:V_i ratio was 6.5 compared with a V_d of 9.4 ± 1.6 µl and a V_d:V_i ratio of 0.9 after direct intracerebral injection. As determined by quantitative autoradiography and -scintillation counting at 24 h after CED, 47.4% of the injected dose per gram tissue (%ID/g) was localized in F98_EGFR gliomas compared with 33.2%ID/g after direct i.t. injection and 12.3%ID/g in F98_WT gliomas. On the basis of these observations, we have concluded that CED is more effective than i.t. injection as a way to deliver boronated EGF to EGFR (+) gliomas for boron neutron capture therapy.

This article has been cited by other articles:

				W. Yang, G. Wu, R. F. Barth, M. R. Swindall, A. K. Bandyopadhyaya, W. Tjarks, K. Tordoff, M. Moeschberger, T. J. Sferra, P. J. Binns, et al. Molecular Targeting and Treatment of Composite EGFR and EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibodies Clin. Cancer Res., February 1, 2008; 14(3): 883 - 891. [Abstract] [Full Text] [PDF]

				G. Wu, W. Yang, R. F. Barth, S. Kawabata, M. Swindall, A. K. Bandyopadhyaya, W. Tjarks, B. Khorsandi, T. E. Blue, A. K. Ferketich, et al. Molecular Targeting and Treatment of an Epidermal Growth Factor Receptor-Positive Glioma Using Boronated Cetuximab Clin. Cancer Res., February 15, 2007; 13(4): 1260 - 1268. [Abstract] [Full Text] [PDF]

				A. Iwamaru, E. Iwado, S. Kondo, R. A. Newman, B. Vera, A. D. Rodriguez, and Y. Kondo Eupalmerin acetate, a novel anticancer agent from Caribbean gorgonian octocorals, induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway Mol. Cancer Ther., January 1, 2007; 6(1): 184 - 192. [Abstract] [Full Text] [PDF]

				W. Yang, R. F. Barth, G. Wu, S. Kawabata, T. J. Sferra, A. K. Bandyopadhyaya, W. Tjarks, A. K. Ferketich, M. L. Moeschberger, P. J. Binns, et al. Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4. Clin. Cancer Res., June 15, 2006; 12(12): 3792 - 3802. [Abstract] [Full Text] [PDF]

				G. Wu, R. F. Barth, W. Yang, S. Kawabata, L. Zhang, and K. Green-Church Targeted delivery of methotrexate to epidermal growth factor receptor-positive brain tumors by means of cetuximab (IMC-C225) dendrimer bioconjugates Mol. Cancer Ther., January 1, 2006; 5(1): 52 - 59. [Abstract] [Full Text] [PDF]

				R. F. Barth, J. A. Coderre, M. G. H. Vicente, and T. E. Blue Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects Clin. Cancer Res., June 1, 2005; 11(11): 3987 - 4002. [Abstract] [Full Text] [PDF]

				W. Yang, R. F. Barth, G. Wu, M. J. Ciesielski, R. A. Fenstermaker, B. A. Moffat, B. D. Ross, and C. J. Wikstrand Development of a Syngeneic Rat Brain Tumor Model Expressing EGFRvIII and Its Use for Molecular Targeting Studies with Monoclonal Antibody L8A4 Clin. Cancer Res., January 1, 2005; 11(1): 341 - 350. [Abstract] [Full Text] [PDF]

				R. F. Barth, W. Yang, A. S. Al-Madhoun, J. Johnsamuel, Y. Byun, S. Chandra, D. R. Smith, W. Tjarks, and S. Eriksson Boron-Containing Nucleosides as Potential Delivery Agents for Neutron Capture Therapy of Brain Tumors Cancer Res., September 1, 2004; 64(17): 6287 - 6295. [Abstract] [Full Text] [PDF]

				M. Vavra, M. J. Ali, E. W.-Y. Kang, Y. Navalitloha, A. Ebert, C. V. Allen, and D. R. Groothuis Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery Neuro-oncol, April 1, 2004; 6(2): 104 - 112. [Abstract] [PDF]