This Article 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 Flessner, M. F. Articles by Dedrick, R. L. Search for Related Content PubMed PubMed Citation Articles by Flessner, M. F. Articles by Dedrick, R. L.

Monoclonal Antibody Delivery to Intraperitoneal Tumors in Rats: Effects of Route of Administration and Intraperitoneal Solution Osmolality

Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute [M. F. F.], and Biomedical Engineering and Instrumentation Program [R. L. D.], National Center for Research Resources, NIH, Bethesda, Maryland 20892

Monoclonal antibody (MAb) transport in peritoneal tissue is dominated by convection, which is dependent on the net driving force of i.p. hydrostatic and osmotic pressure. To test the hypothesis that the i.p. osmolality has significant effects on IgG delivery to the tumor during the acute period after injection, solid tumors (FEMX-II) were transplanted into the anterior abdominal wall of nude rats. The wall is subject to well-defined pressure forces from the solution in the cavity. MAb 96.5, which specifically binds to FEMX-II cells, was simultaneously injected i.v. (¹¹¹In-MAb 96.5 in Krebs Ringer solution) and i.p. (¹²⁵I-MAb 96.5 in dialysis solution). Intraperitoneal hydrostatic pressure was held constant, and the osmolality of the i.p. solution was varied between isotonic and hypertonic (with the addition of 4% mannitol to an isotonic salt solution) in order to vary the direction of net convection. Plasma and peritoneal concentrations of both isotopes were measured at intervals over 200 min, and tissue concentration profiles in tumor and adjacent normal tissue were determined by dual-label quantitative autoradiography at 200 min. After i.v. administration, profiles were relatively flat and little affected by i.p. osmolality. After i.p. injection, profiles demonstrated steep concentration decreases from the peritoneal surface into the tissue for several hundred µm. Despite the change from the condition of water absorption from the cavity into the body (isotonic solution) to one of net volume gain by the cavity (hypertonic solution), tumor profiles were affected by i.p. osmolality only near the surface. Specific binding properties of the tumor were determined for the tumors studied and were consistent with high surface concentrations relative to normal tissue. Variation of the i.p. solution osmolality by changes in concentration of small molecules exerts only minor effects on the short-term MAb delivery from either systemic or regional administration to a target tumor in the anterior abdominal wall in the rat.

¹ To whom requests for reprints should be addressed, at University of Rochester School of Medicine and Dentistry, Strong Memorial Hospital, 601 Elmwood Ave, Box 675, Rochester, NY 14642.

Received 1/20/94. Accepted 6/14/94.

This article has been cited by other articles:

				J. Choi, K. Credit, K. Henderson, R. Deverkadra, Z. He, H. Wiig, H. Vanpelt, and M. F. Flessner Intraperitoneal immunotherapy for metastatic ovarian carcinoma: resistance of intratumoral collagen to antibody penetration. Clin. Cancer Res., March 15, 2006; 12(6): 1906 - 1912. [Abstract] [Full Text] [PDF]

				M. F. Flessner, J. Choi, K. Credit, R. Deverkadra, and K. Henderson Resistance of Tumor Interstitial Pressure to the Penetration of Intraperitoneally Delivered Antibodies into Metastatic Ovarian Tumors Clin. Cancer Res., April 15, 2005; 11(8): 3117 - 3125. [Abstract] [Full Text] [PDF]

				M. F. Flessner, J. Choi, Z. He, and K. Credit Physiological characterization of human ovarian cancer cells in a rat model of intraperitoneal antineoplastic therapy J Appl Physiol, October 1, 2004; 97(4): 1518 - 1526. [Abstract] [Full Text] [PDF]

				M. R. Hamblin, J. L. Miller, I. Rizvi, B. Ortel, E. V. Maytin, and T. Hasan Pegylation of a Chlorine6 Polymer Conjugate Increases Tumor Targeting of Photosensitizer Cancer Res., October 1, 2001; 61(19): 7155 - 7162. [Abstract] [Full Text] [PDF]

				M. F. Flessner Transport of protein in the abdominal wall during intraperitoneal therapy. I. Theoretical approach Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G424 - G437. [Abstract] [Full Text] [PDF]

				P. A. Netti, L. M. Hamberg, J. W. Babich, D. Kierstead, W. Graham, G. J. Hunter, G. L. Wolf, A. Fischman, Y. Boucher, and R. K. Jain Enhancement of fluid filtration across tumor vessels: Implication for delivery of macromolecules PNAS, March 16, 1999; 96(6): 3137 - 3142. [Abstract] [Full Text] [PDF]

				M. F. Flessner, J. Lofthouse, and E. R. Zakaria In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2783 - H2793. [Abstract] [Full Text] [PDF]