Use of the rat pancreatic CA20948 cell line for the comparison of radiolabelled peptides for receptor-targeted scintigraphy and radionuclide therapy

We have evaluated the usefulness of the rat pancreatic CA20948 tumour as an in vitro cell culture model and as an in vivo model in Lewis rats comparin g different radiolabelled peptides for receptor-targeted scintigraphy. In v itro the receptor-specific uptake and internalization of different radiolab elled analogues of somatostatin, bombesin, substance P and cholecystokinin were demonstrated. Analogues were selected based on high-affinity binding t o their respective receptors. Their uptake and internalization in CA20948 c ells were compared to these processes in AR42J cells, a well-known rat panc reatic tumour cell line used for peptide-receptor studies. Receptor-specifi c internalization, which was blocked by excess unlabelled peptide analogue, was found in both the CA20948 and AR42J cells for all the peptide analogue s tested. This indicates specific receptor expression for all the different peptides, making these cells highly suitable for peptide studies. Internal ization of the different peptides was as follows, in increasing order: [In- 111-DOTA(0)]CCK <[In-111-DTPA(0),Arg(1)]substance P <[In-111-DTPA(0)]octreo tide <[In-111-DTPA(0),Pro(1),Tyr(4)]bombesin. Internalization appeared to b e time and temperature dependent. In accordance with the in vitro experimen ts, receptor-specific uptake of all the peptide analogues was also found in vivo in the solid CA20948 tumour. The in vivo tumour uptake of [In-111-DTP A(0)]octreotide was the highest amongst the peptides tested, the order of t umour uptake being [In-111-DTPA(0)]octreotide >[In-111-DTPA(0),Pro(1),Tyr(4 )]bombesin > [In-111-DTPA(0),Arg(1)]substance P >[In-111-DOTA(0)]CCK, which is different from the in vitro findings and points to Either different rec eptor numbers on the tumour cells for the different peptide receptors in vi tro and in vivo or to differences between the peptides with regard to metab olic stability. It can be concluded that the CA20948 tumour, both in cell c ulture and as a solid tumour in rats, is a very useful model for peptide re ceptor scintigraphy and radionuclide therapy studies. ((C) 2000 Lippincott Williams & Wilkins).