Eric P. Krenning

Internalization of radiolabelled [DTPA0]octreotide and [DOTA0,Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy.

We compared the internalization of [90Y-DOTA0,Tyr3]octreotide and [111In-DOTA0,Tyr3]octreotide with that of [125I-Tyr3]octreotide and [111In-DTPA0]octreotide in the subtype 2 somatostatin receptor (sst2)-positive rat pancreatic tumour cell lines CA20948 and AR42J and in the somatostatin receptor-negative human anaplastic thyroid tumour cell line ARO. We demonstrated that [111In-DTPA0]octreotide, [90Y-DOTA0,Tyr3]octreotide and [111In-DOTA0,Tyr3]octreotide are internalized by a receptor-specific, time- and temperature-dependent process. The amount of [90Y-DOTA0,Tyr3]octreotide internalized was higher than that of [111In-DOTA0,Tyr3]octreotide and [111In-DTPA0]octreotide.

Radioiodinated somatostatin analogue RC-160: preparation, biological activity, in vivo application in rats and comparison with [123I-Tyr3]octreotide.

We have evaluated the potential usefulness of the radioiodinated octapeptide RC-160, a somatostatin analogue, which might serve as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose, iodine-123 and iodine-125 labelled RC-160 was tested for biological activity and applied in vivo in rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. Our group has recently described the in vivo visualization of such tumours in rats and in humans with the radioiodinated somatostatin analogue [Tyr3]octreotide. Like [123I-Tyr3]octreotide, 123I-RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours. However, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. We therefore conclude that in this animal model 123I-RC-160 has no advantage over [123I-Tyr3]octreotide as a radiopharmaceutical for the in vivo use as a somatostatin receptor imager, although, like [123I-Tyr3]octreotide, 123I-RC-160 shows specific binding to different somatostatin receptor-positive organs. Recently differences were reported in affinity between somatostatin and its analogues for somatostatin receptors expressed in different human cancers, like those of the breast, ovary, exocrine pancreas, prostate and colon. Therefore 123I-RC-160 might be of interest for future use in humans as a radiopharmaceutical for imaging octreotide receptor-negative tumours.