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

The grafted human glioblastoma cell CB109 was used as a model for intralesi onal therapy with I-131-labelled hyaluronectin glycoprotein (I-131-HN). I-1 31-HN bound specifically to in situ hyaluronic acid (HA); a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 mu Ci/mu gHN, 1 m u g chloramine-T/mu gHN and a 60-s stirring period provided a I-131-HN prep aration with an optimal affinity for HA (64% compared to unlabelled HN). Fo llowing intratumoral injection, I-131-HN was retained with a limited diffus ion outside the tumour. On day 4 the radioactivity concentrated in the tumo ur was still 25 times greater than that in the liver, spleen and kidneys co mbined. For therapeutic assays, 65 mu Ci I-131-HN was injected into the tum our, resulting in a delivery of 6.8 Gy over a 7-day period. Controls receiv ed unlabelled HN, heat-inactivated HN: a mixture of inactivated HN plus fre e I-131 or no treatment (six animals per group). Tumour volumes were evalua ted every second day from treatment day and the rate of tumour growth was e xpressed 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 o r without free I-131 had anti-tumour effect. Unlabelled HN-injected tumours had a slightly slower growth rate than untreated tumours (p < 0.02) and gr owth rate of I-131-HN-injected tumours was much lower (p < 0.00002). A pron ounced inhibitory effect with intralesional I-131-labelled HN injection res ulted 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.