The effect of specimen processing on radiolabeled monoclonal antibody biodistribution

Wahl, Richard L.; Sherman, Philip S.; Fisher, Susan J.

doi:10.1007/bf00252876

Cited by 13 publications

(10 citation statements)

References 8 publications

(7 reference statements)

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“…12sI UPC-IO injection the sedated rats (n = 14) were injected with either normal saline intravenously (25OpL) or with 250 pg (25OpL) of the affinity purified goat anti-mouse IgG intravenously. Animals continued to have blood samples obtained (in these animals the peritoneal fluid was not reliably obtained beyond 10 h post-injection due to absorption) following their regaining consciousness 10 h post UPC-10 injection, and they were subsequently sacrificed with tissue radioactivity levels and sample weights determined 24 h following 1251 UPC-IO injection using standard tissue handling techniques (Wahl et al, 1984). In another set of experiments, rats received the lz51 UPC-10 intraperitoneally, but received a 250 pg of affinity-purified goat antimouse antibody dose intravenously 1.5 h post-intraperitoneal radioantibody injection.…”

Section: Methodsmentioning

confidence: 99%

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

Wahl

Fisher

1987

International Journal of Radiation Applications and Instrumenta

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Radiolabeled monoclonal antibodies (MAb) delivered intraperitoneally expose cells in contact with peritoneal fluid to considerably higher levels of MAb than if the MAb dose were given intravenously. This regional delivery advantage for intact MAb is present mainly due to the relatively slow exit of MAb from the peritoneal fluid to the blood. Eventually, following i.p. injection, blood levels of MAb rise resulting in exposure of the animal to high systemic MAb levels and potential toxicity. In this series of experiments, systemic exposure was minimized by the administration of unlabeled goat polyclonal anti-mouse antibody intravenously from 1 1/2 to 6 h following i.p. MAb injection. This maneuver results in the formation of immune complexes with their subsequent clearance and dehalogenation by the reticuloendothelial system, thus minimizing systemic MAb exposure. This approach, of increasing systemic clearance of MAb, did not alter intraperitoneal MAb levels and thus significantly increased the regional delivery advantage to the peritoneal cavity by 70-100%. This approach provides an immunologic rationale for the further enhancement of MAb delivery to i.p. foci of malignant disease and may have diagnostic and therapeutic utility.

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Section: Methodsmentioning

confidence: 99%

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

Wahl

Fisher

1987

International Journal of Radiation Applications and Instrumenta

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“…At 7-10 days post-injection, animals were killed and their tissues were weighed and counted for -J1I and Lí:>l activity in a gamma counter. After correction for 1JiI to "->I spillover, the tumor/non-tumor ratios of each isotope were determined (13)(14)(15). Statistical analysis was by the student's and paired t-tests.…”

Section: Nude Mouse Modelmentioning

confidence: 99%

Radioimmunodiagnosis of Human-Derived Squamous Cell Carcinoma

Wahl¹,

Kimmel²,

Beierwaltes³

et al. 1987

Hybridoma

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Squamous cell carcinomas (SCC) of the head and neck are common and aggressive tumors. A murine IgG 2aK monoclonal antibody (A9) reactive with most SCCs was radiolabeled with I-131 and tested for localization and imaging ability in groups of nude mice bearing SCC tumors derived from two patients with head and neck cancer (UM-SCC-2 and UM-SCC-11B). The mice also received I-125 labeled isotype-matched control antibody UPC-10 for double-label counting. Animals were imaged at multiple time points post-injection and sacrificed 7-10 days later for assessment of the tissue distribution of the radiopharmaceuticals. In general, the tumors were visualized satisfactorily on gamma camera images of both the UM-SCC-2 and UM-SCC-11B tumor-bearing animals. While localization of the A9 antibody was mainly due to antibody specificity in the UM-SCC-2 tumor-bearing animals, there was also a large component of non-specific antibody localization in the UM-SCC-11B bearing animals. This may be due to greater central fluid space and or necrosis in the UM-SCC-11B tumors. This study demonstrates the feasibility of imaging human-derived squamous cell carcinomas with radiolabeled monoclonal antibody A9 and holds forth the possibility of therapy of this radiosensitive tumor in a like manner.

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“…This would obviously enhance imaging and increase the possibility of successful radioimmunotherapy with radiolabeled antibody. In the present study we evaluated the feasibility of enhancing specific antibody tumor/background levels/g of injected antibody in selected tissues were ratios by experimentally attempting to achieve the total removal of circulating blood pool ratioantibody determined using standard tissue counting methods (Wahl et al, 1984). In nude mice with HTB77 tumors from normal and tumor-bearing animals by exhaustive perfusion with saline.…”

Section: Introductionmentioning

confidence: 99%

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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The effect of specimen processing on radiolabeled monoclonal antibody biodistribution

Cited by 13 publications

References 8 publications

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

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

Radioimmunodiagnosis of Human-Derived Squamous Cell Carcinoma

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

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