Intravesical administration of indium‐111‐labelled hmfg2 monoclonal antibody in superficial bladder carcinomas

Abstract

Tumour-associated HMFG2 monoclonal antibody (MAb) was labelled with indium-111 and administered intravesically to 20 patients with known or suspected superficial bladder carcinoma. The antibody solution was kept in the bladder for 1 hr and was then washed out. Cystoscopy was performed at 2 and 24 hr after instillation. Radioactivity of tumour and normal tissue obtained from the bladder during cystoscopy and cells recovered from urine after the instillation were counted in a gamma-counter. Conventional histology, immunocytochemistry and autoradiography were also performed. Mean uptake at 2 and at 24 hr was higher in tumours than in normal samples. Autoradiography showed selective accumulation of radioactivity in cells which expressed the antigen detected by the HMFG2 MAb. There was no correlation of tumour uptake with the grade of tumour. No radioactivity was found in the blood of patients after the instillation. Based on dosimetric calculations, however, the radiation dose that can be delivered to the tumours is not sufficient to be cytotoxic, possibly due to inadequate penetration and retention by tumour tissue. Nevertheless, the significant difference between antibody uptake by the tumours and that by normal urothelium, observed in our study, allow for the possibility of using this approach therapeutically.

Photosensitized singlet oxygen and its applications

“…It is known that tumor cells have cell surface antigens that are different from those of normal cells. If the mAB bound photosensitizer will bind specifically to the tumor tissue, this would allow selective photodamage without affecting normal tissue [82]. The current strategy for binding photosensitizers uses polyphasic tumor therapy to accumulate up to 10 8 photosensitizer molecules on the tumor, assuming ca.…”

Intravesical Administration of EGF– Dextran Conjugates in Patients with Superficial Bladder Cancer

“…When the size of the tumor was taken into consideration, studies by Bamias et al [4]reported no correlation between uptake and size of the tumor. In our series, a considerable accumulation of radioactivity was observed in larger neoplasms.…”

“…The selection of the ligand should be tailored to the characteristics of the tumor type studied. For urinary bladder cancer several conjugates have been constructed based on Mab as tumor–seeking molecule [3, 4, 11, 12, 13]. However, no specific bladder cancer–derived antibody has been reported.…”

“…Intravesical administration of tumor–associated monoclonal antibodies (Mab) has been used for tumor targeting [3, 4]. Tumor uptake was low, presumably due to insufficient penetration of tumor papillae by antibodies and low specificity.…”

Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma

“…New radioimmunotherapeutical conjugates have been developed in the last 15 years with the prospect of treating bladder cancer through such procedures. Most of these involved antibodies radiolabelled with 111 In (8,9), 131 I (10), 67 Cu (11,12), 188 Re (13). However, the large size of monoclonal antibodies (~150 kD) is a general limitation to the efficiency of intravesical treatments due to slow diffusion and limited penetration.…”