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 (p < 0.05). 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) (p < 0.05). Control
injections did not affect the
tumor/blood ratio, but increased the uptake of 125I-labeled
TP-3 significantly in kidney and spleen (p < 0.05). Also, BTH reduced the uptake of 125I-labeled UPC-10 in
tumor and liver by approximately 20% compared with controls (p < 0.05). 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.