Intraperitoneal delivery of monoclonal antibodies: Enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody

Wahl, Richard L.; Fisher, Susan J.

doi:10.1016/0883-2897(87)90034-1

Cited by 6 publications

(9 citation statements)

References 9 publications

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“…The faster systemic clearance of Fab can be mimicked to improve the Rd of intact IgG, as has been shown in experiments in which we have accelerated the systemic clear- ance of iodinated intact IgG by using a polyclonal antimouse antibody given systemically [21]. This approach, which presumably forms radioactive immune complexes which are then catabolized by the liver, considerably diminishes systemic exposure to radioantibody without measureable impact on i.p.…”

Section: Discussionmentioning

confidence: 82%

“…We have recently shown for radioiodinated intact murine IgG2ak, that increased antibody concentration compared to blood levels exists in the peritoneal cavity of rats following i.p. antibody administration [21,24]. We also showed that this i.p.…”

Section: Introductionmentioning

confidence: 88%

“…These experiments were performed for all antibodies and fragments (except that the UPC-10 (data previously reported) [21] and BA-1 were studied only following i.p. administration and then to only 24 h after injection).…”

Section: Time Course Experimentsmentioning

confidence: 99%

“…We also showed that this i.p. delivery advantage could be further enhanced by accelerating the clearance of the intact IgG from the blood stream using a systemically administered polyclonal anti-mouse antibody [21]. Through such a manipulation, the Rd advantage following i.p.…”

Section: Introductionmentioning

confidence: 99%

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The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage

Wahl

Barrett

Geatti

et al. 1988

Cancer Immunol Immunother

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The i.p. delivery of murine monoclonal antibody was compared with i.v. delivery in normal mice and rats, in normal nude mice and in those with i.p. human ovarian carcinoma xenografts. In normal rats, all classes of antibodies and antibody fragments evaluated were cleared from the peritoneal cavity at comparable rates. The regional delivery (Rd1) advantage to the peritoneal cavity following i.p. delivery was thus most dependent on the rate of clearance of the antibody or fragment from the blood stream. Determining the exact i.p. delivery advantage was problematic due to the difficulty in reliably obtaining peritoneal fluid later than 9-10 h after i.p. injection in normal animals. During the first 9 h following i.p. injection, the Rd(0-9/0-9) was, for a murine IgG2ak Fab greater than F(ab')2 greater than IgG (at 13.6 greater than 10 greater than 7.9). Two murine IgMs evaluated differed in Rd(0-9) at 27.1 and 9.2 respectively. When blood levels were extrapolated to infinity, these Rd (0-9/affinity) values were considerably lower with the Fab having the highest Rd at 4.67. The i.p. Rd advantage was almost solely due to the i.p. antibody levels seen in the first 24 h after injection, as after that time, blood levels become comparable to those seen following i.v. injection. Normal tissues obtained at sacrifice 5-7 days after i.p. injection. Normal tissues obtained at sacrifice 5-7 days after i.p. or i.v. injection in rats showed comparable levels of radioantibody activity, whether the injection was i.p. or i.v. (except for higher diaphragmatic levels following i.p. delivery). In nude mice with i.p. human-derived ovarian tumors, intact IgG clearance from the peritoneal cavity to the blood was considerably slower than in normal animals, and early i.p. tumor uptake of specific antibody was significantly higher than that following i.v. antibody delivery. With higher early tumor uptake and lower systemic exposure, early tumor/nontumor ratios were significantly greater than those for i.v. delivery, though not beyond 48 h after i.p. injection. This study demonstrates the pharmacokinetic rationale for i.p. monoclonal antibody delivery, especially for agents cleared rapidly from the blood, such as antibody fragments. In addition, definite i.p. delivery benefit for antibody specific to i.p. tumors in the i.p. ovarian cancer system was shown soon after injection. These data regarding i.p. antibody delivery should be useful in rationally planning diagnostic and therapeutic studies involving the i.p. delivery of unmodified and immunoconjugated monoclonal antibodies.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 88%

Section: Time Course Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage

Wahl

Barrett

Geatti

et al. 1988

Cancer Immunol Immunother

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“…Because of its high propensity to stay confined to the peritoneal cavity until very late in the course of the disease, radiolabeled antibodies have been administered intraperitoneally in most trials. Indeed, in several preclinical and clinical studies it was demonstrated that the intraperitoneal route of administration results in higher uptake of radiolabeled antibodies in tumor as compared to the intravenous route of administration [121][122][123][124][125][126]. Other authors, however, could not confirm an advantage of intraperitoneal over intravenous administration [127].…”

Section: Ovarian Cancermentioning

confidence: 96%

Antibody-guided radiation therapy of cancer

Koppe

Postema²,

Aarts

et al. 2005

Cancer Metastasis Rev

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Radioimmunotherapy (RIT) using radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens has evolved from an appealing concept to one of the standard treatment options for patients with non-Hodgkin's lymphoma (NHL). Inefficient localization of radiolabeled MAbs to nonhematological cancers due to various tumor-related factors, however, has refrained RIT from outgrowing the experimental stage in solid tumors. Still, small volume or minimal residual disease has been recognized as a potentially suitable target for radiolabeled antibodies. Several strategies are being explored aimed at improving the targeting of radiolabeled MAbs to solid tumors thus improving their therapeutic efficacy. In this review, a historical overview of the application of RIT is given and various aspects of the application of radiolabeled MAbs as anti-cancer agents are discussed. Finally, the clinical results of RIT of NHL, colorectal cancer, ovarian cancer, breast cancer, and renal cell cancer are reviewed.

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Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

Wahl

Piko

Beers

et al. 1988

International Journal of Radiation Applications and Instrumenta

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We evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Initially, groups of rats were injected intravenously (i.v.) with 131I-5G6.4 MoAb (murine IgG2aK reactive with ovarian carcinoma). These animal's radioactivity levels were determined by dose calibrator and they were imaged before and after perfusion which was conducted at 4 or 24 h post-antibody injection. Animals were sacrificed after perfusion, as were controls, and normal organ radioactivity levels determined. In addition, nude mice bearing HTB77 ovarian cancers subcutaneously were injected i.v. with 131I-5G6.4 MoAb and were imaged before and after systemic perfusion with saline 24 h post-5G6.4 injection. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times (P less than 0.0005). The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +/- 5.1%) than for those perfused at 24 h post i.v. antibody injection (32.9 +/- 2.9%) (P less than 0.025). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively (by computer image analysis) enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor (P less than 0.05). These studies show that (1) much background antibody radioactivity can be removed using whole-body perfusion with saline, (2) that the decline in whole body activity is larger with 4 than 24 h perfusion and (3) tumor imaging can be enhanced by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

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Intraperitoneal delivery of monoclonal antibodies: Enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody

Cited by 6 publications

References 9 publications

The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage

The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage

Antibody-guided radiation therapy of cancer

Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

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