No abstract

Forty-five patients known or suspected to have transitional cell carcinoma of the urinary bladder underwent intravesical administration of either AUA1 tumor-associated monoclonal antibody or 11.4.1. nonspecific monoclonal antibody. Antibodies were radiolabeled with iodine-131, diluted in 50 ml normal saline and remained in the bladder for up to 1 h. During cystoscopy or transurethral resection of the tumor, tissue samples were taken from normal and malignant areas and were counted for radioactivity in a gamma counter. Blood samples were also measured for radioactivity. Mean uptake of AUA1 at 2, 20, 40 and 60 h after administration (expressed as 10(3) x percentage of injected dose/gram of tissue) was: 1.77 +/- 3.2, 1.28 +/- 1.67, 0.72 +/- 0.94 and 0, respectively in the tumor and 0.79 +/- 0.83, 0.14 +/- 0.34, 0.033 +/- 0.06 and 0 in normal tissue. Mean uptake of 11.4.1 at 2 and 20 h was: 0.47 +/- 0.42 and 0.018 +/- 0.015, respectively, in tumor and 0.2 +/- 0.19 and 0.013 +/- 0.002 in normal samples. No remarkable radioactivity was found in blood samples. Conventional and immunoperoxidase staining were also performed. Mean uptake of AUA1 by the tumor increased as the degree of tumor differentiation decreased. Our findings indicate that intravesical administration of AUA1 results in selective immunolocalization of AUA1 in intermediate and high-grade transitional cell carcinoma. This may allow the development of a new method for bladder carcinoma treatment or prophylaxis against recurrence.

The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3-6 mCi (111-222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with single-photon emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12-20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFG1 monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using 99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%-9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of 99mTc-HMFG1 monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.

C. A r c h i m a n d r i t i s l ' , J u l i a M a l a m i t s i 2 , E l i a s Belkasl , Alexandra D. Varvarigou' , K y r i a k o s C o t s y f a k i s l , Gregory Sivolapenko3, John Zorzos4, Demosthenes V . Skarlos5 and Charalambos P r o u k a k i s 2 . SUMMARY The present study r e f e r s t o t h e p r e p a r a t i o n o f a 99m-Technetium l a b e l l e d murine monoclonal a n t i b o d y f o r c l i n i c a l a p p l i c a t i o n . The monoclorla a n t i b o d y was incubated w i t h a 2 0 f o l d molar excess of 2-iminoth olane. The f r e e t h i o l groups c r e a t e d , were capable o f b i n d i n g reduced technetium. L a b e l l i n g took p l a c e through an exchange r e a c t i o n w i t h 99m-Technetium-Glucoheptonate. The l a b e l l i n g c o n d i t i o n s were s t u d i e d e x t e n s i v e l y . Diverse chromatographic methods (ITLC, HPLC) were developed i n o r d e r t o study t h e Address any correspondance t o : * D r . S . C . A r c h i m a n d r i t i s ,

Ten patients with transitional cell carcinoma (TCC) of the bladder received 3-6 mCi of HMFG1 monoclonal antibody (MAb) intravesically. The antibody was labeled with Tc-99m using the 2-Iminothiolane method. All patients underwent transurethral resection of the bladder tumor within 12-20 h following intravesical administration of 99m-Tc-HMFG1. The presence of the radiolabeled MAb in the circulation was studied by measuring the radioactivity in the serum for a period up to 20 h. Three of 10 patients underwent immunoscintigraphy (SPECT) 2-3 h postadministration and cancerous areas could be easily localized. Biopsies were taken from the tumor sites as well as from normal bladder mucosa. Absolute uptake of the administered MAb expressed as percent administered dose/kg of tissue could be evaluated only in eight patients. Multiple specimen taken from various tumor sites in every patient gave a wide range of uptake values ranging from 0 to 9.29% adm. dose/kg, whereas normal tissue uptake values ranged from 0 to 1.63, respectively.