Indium ¹¹¹In pentetreotide

Indium ¹¹¹In pentetreotide attaches to somatostatin receptors (mainly subtype 2 and subtype 5) in tissues where, as consequence of disease, the cell-surfaces contain these receptors in a more than physiologic density. In individual patients, where the disease did not lead to an increased receptor density, scintigraphy will not be successful.

In carcinoids and GEP-tumours the prevalence of increased receptor density in the tumour-tissue in general is rather high.

Only limited studies of pharmacodynamic effects have been performed. The in vitro biological activity is approximately 30% of the biological activity of natural somatostatin. The in vivo biological activity, measured in rats, is less than that of equal amounts of octreotide. Intravenous administration of 20 g of pentetreotide resulted in some patients in a measurable but very limited decrease of serum gastrin and serum glucagon levels of less than 24 hours duration.

Organ uptake

Indium(¹¹¹In)pentetreotide is taken up by the following organs: liver (approximately 2% at 24 hours) and spleen (approximately 2.5% at 24 hours). Uptake in thyroid and pituitary occurs but not reproducibly. The uptake in kidneys is partly a reflection of ongoing elimination through the urine and partly due to delayed excretion by the kidney.

Elimination

Indium(¹¹¹In)pentetreotide not bound to receptors, and non-peptide bound indium(¹¹¹In), is rapidly eliminated through the kidneys. Within 24 hours after intravenous administration, approximately 80% of the radiolabelled pentetreotide is eliminated through the urinary system. After 48 hours 90% is excreted. The elimination via the gallbladder and subsequently the faeces is approx. 2% of the administered activity in patients with normal intestinal function.

Up to 6 hours post-administration radioactivity in urine is predominantly intact indium(¹¹¹In)pentetreotide. Thereafter, increasing amounts of non-peptide-bound activity are excreted.

Half life

¹¹¹In decays with a half-life of 2.83 days to stable cadmium.

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. No testing has been done on carcinogenic potential nor of the influence of pentetreotide on fertility or on embryotoxicity.