Therapeutic efficacy of intralesional 131I-labelled hyaluronectin in grafted human glioblastoma

Abstract

The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN).131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in turnout invasion. Labelling experimental conditions were determined and, finally, 25 μCi/μgHN, 1 μg chloramine-T/μgHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the turnour. On day 4 the radioactivity concentrated in the turnour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 μCi 131I- HN was injected into the turnour, resulting in a delivery of 6.8 Gy over a 7- day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free 131I or no treatment (six animals per group). Turnour volumes were evaluated every second day from treatment day and the rate of turnour growth was expressed as a ratio of tumour size at time intervals to the tumour size at the time of injection. Growth curves were compared: heat-inactivated with or without free 131I had no anti-tumour effect. Unlabelled HN-injected turnouts had a slightly slower growth rate than untreated turnouts (p < 0.02) and growth rate of 131I-HN-injected turnouts was much lower (p < 0.00002). A pronounced inhibitory effect with intralesional 131I-labelled HN injection resulted from a combination of a) blockage of HA, a proliferation facilitating factor, and b) local irradiation of tumoral tissue, while uptake in normal tissues was minimized.