Hyaluronidase-induced periodic modulation of the interstitial fluid pressure increases selective antibody uptake in human osteosarcoma xenografts

摘要: Abstract Periodic modulation of the elevated interstitial fluid pressure might improve filtration and uptake tumor-targeting macromolecules (e.g. radioimmunoconjugates) in solid tumors. Cycling tumor was initiated by intratumoral injections bovine testicular hyaluronidase (BTH, 1,600 U) osteosarcoma-bearing nude mice. BTH injection repeated at 3-day intervals up to 9 days, conjunction with tail vein 125I-labeled TP-3 monoclonal antibody against an osteosarcoma-associated antigen (n = 9) or non-specific UPC-10 9). Control mice received phosphate buffered saline 18). The radioactivities normal tissues (blood, liver, kidney spleen) were measured compared between different groups. increased specific significantly approximately 70% receiving 3 fractions 1-2 (p < 0.05). tumor/normal tissue ratio 5) higher for all tissues, 4) did not affect tumor/blood ratio, but spleen Also, reduced liver 20% controls results indicate that periodic lowering increase specificity blood-borne antibodies tumors vivo.