Autor: |
C, Brekken, M H, Hjelstuen, Ø S, Bruland, C, de Lange Davies |
Rok vydání: |
2000 |
Předmět: |
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Zdroj: |
Anticancer research. 20(5B) |
ISSN: |
0250-7005 |
Popis: |
Periodic modulation of the elevated interstitial fluid pressure might improve filtration and uptake of tumor-targeting macromolecules (e.g. radioimmunoconjugates) in solid tumors. Cycling of the tumor interstitial fluid pressure was initiated by intratumoral injections of bovine testicular hyaluronidase (BTH, 1,600 U) in osteosarcoma-bearing nude mice. BTH injection was repeated at 3-day intervals up to 9 days, in conjunction with tail vein injections of 125I-labeled TP-3 monoclonal antibody against an osteosarcoma-associated antigen (n = 9) or non-specific 125I-labeled UPC-10 antibody (n = 9). Control mice received intratumoral injections of phosphate buffered saline (n = 18). The radioactivities of tumor and normal tissues (blood, liver, kidney and spleen) were measured and compared between the different groups. BTH injections increased the tumor uptake of specific 125I-labeled TP-3 significantly by approximately 70% in mice receiving 3 fractions compared to 1-2 fractions of the antibody (p0.05). The tumor/normal tissue ratio in mice receiving 3 fractions of 125I-labeled TP-3 (n = 5) was significantly higher for all tissues, compared with mice receiving 1-2 fractions (n = 4) (p0.05). Control injections did not affect the tumor/blood ratio, but increased the uptake of 125I-labeled TP-3 significantly in kidney and spleen (p0.05). Also, BTH reduced the uptake of 125I-labeled UPC-10 in tumor and liver by approximately 20% compared with controls (p0.05). The results indicate that periodic lowering of the tumor interstitial fluid pressure might increase the specificity of blood-borne monoclonal antibodies to solid tumors in vivo. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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