EFFECTS OF PROTON IRRADIATION ON RADIOLABELED MONOCLONAL-ANTIBODY UPTAKE IN HUMAN COLON-TUMOR XENOGRAFTS

A major limitation of radiolabeled monoclonal antibodies (MAbs) for ca ncer imaging and therapy is their low accumulation within solid tumors . We, and others, have previously shown that pretreatment of a tumor m ass with gamma radiation can increase the level of radiolabeled MAb at the tumor site. Unlike that of conventional radiation, the dose distr ibution of protons allows for increasing the dose to the cancer volume while reducing the normal tissue dose. The Proton Radiation Therapy F acility at LLUMC treats patients and conducts research. In this study, we sought to determine if preirradiation with proton beam can enhance the localization of radiolabeled MAb within xenotransplanted human co lon tumors. T380 colon tumors, implanted s.c. into athymic mice, were subjected to proton irradiation (10 Gy, single dose) when mean tumor v olume was 125-135 mm(3)/group. In-111-ZCE025, a murine MAb directed ag ainst carcinoembryonic antigen, was injected i.p. 2 h later, and biodi stribution studies were performed 38 h thereafter. Animals irradiated with Co-60 and given either In-111-ZCE025 or In-111-MOPC21, an irrelev ant MAb, served as controls. The mean percentage of injected radioacti vity localized within tumors was highest in the group treated with pro tons + In-111-ZCE025 when expressed on a per gram basis (%ID/g = 19.3) . Somewhat unexpectedly, higher radioactivity was also noted in the no rmal tissues of these animals compared to other groups. The mean %ID/g tumor values for those given Co-60 + In-111-ZCE025 or the antibody al one were 12.5 and 9.0. Our data show that preirradiation of solid tumo rs increases the localization of tumor-specific radiolabeled MAb at th e tumor site. Enhancements of 214 and 139% were seen with protons and Co-60, respectively, compared to no irradiation. The higher radioactiv ity found in normal tissues of proton-treated mice may be related to d ifferences in the relative biological effect between the two types of radiation used.