INCORPORATION OF IODODEOXYURIDINE IN MULTICELLULAR GLIOMA SPHEROIDS -IMPLICATIONS FOR DNA-TARGETED RADIOTHERAPY USING AUGER-ELECTRON EMITTERS

A promising new treatment for glioma involves Auger electron emitters such as I-125 or I-123 conjugated to deoxyuridine (IUdR). However, the presence in tumour deposits of non-proliferating cells with clonogeni c potential poses a major limitation to this cycle-specific therapy. W e have used multicellular tumour spheroids derived from the human glio ma cell line UVW to study [I-125]UdR-targeted radiotherapy in aggregat es containing cells in different proliferative states. Autoradiographi c identification of labelled cells indicated that nuclear incorporatio n of [I-125]IUdR decreased markedly with increasing size of spheroid. IUdR incorporation was maximal in the surface layer of cells and decre ased with depth within spheroids. Radiopharmaceutical uptake correspon ded closely to the regions of cell cycling as indicated by staining fo r the nuclear antigen Ki67. The uptake of drug was enhanced by increas ing the duration of incubation from 52 h to 104 h. These observations suggest that significant sparing of non-cycling malignant cells would result from treatment delivered as a single injection of radiolabelled IUdR. To achieve maximal therapeutic effect, IUdR should be administe red by multiple injections, by slow release from biodegradable implant s or by slow-pump delivery.