- 14 amino acid peptide.
- Physiologic regulation of hormones and organs in the body: the effects of somatostatin are mediated by G-protein coupled membrane receptors.
- 5 different human somatostatin receptor subtypes: sst1, sst2, sst3, sst4, sst5.
- Somatostatin binds to all receptor subtypes with high affinity.
- Octreotide: 8 amino acid somatostatin analog.
- Octreotide binds to somatostatin receptors on cell surfaces throughout the body. It binds with high affinity to sst2 and with lower affinities to sst3 and sst5 (no binding to sst1 and sst4).
- Radioactivity leaves the plasma rapidly: one third of the radioactive dose remains in the blood pool at 10 minutes after intravenous administration. Within an hour of injection, most of the dose of 111-In-pentetreotide distributes from plasma to extravascular body tissues and concetrates in tissues containing a high density of somatostatin receptors. Plasma levels continue to decline so that by 20 hours post-injection, about 1% of the radioactive dose is found in the blood pool. The biological half-life of 111-In-pentetreotide is 6 hours.
- For several hours after administration, plasma radioactivity is predominantly in parent form. 10% of the radioactivity excreted is nonpeptide - bound.
- After background clearance, visualization of somatostatin receptor - rich tissue is achieved. In addition to somatostatin receptor - rich tumors, the normal pituitary gland, thyroid gland, liver, spleen and urinary bladder also are visualized in most patients, as is the bowel to a lesser extent.
- Excretion is almost exclusively via the kidneys. Half of the injected dose is recoverable in urine within six hours after injection, 85% is recovered in the first 24 hours and over 90% is recovered in urine by two days.
- Hepatobiliary excretion represents a minor route of elimination and less than 2% of the injected dose is recovered in feces within three days after injection.
- Scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors.
- The molecular basis of the use of 111-In-pentetreotide is receptor - mediated internalization and cellular retention of the drug.
- Internalization of 111-In-pentetreotide is receptor specific and temperature dependent.
- Receptor - mediated internalization of 111-In-pentetreotide results in degradation to the final radiolabeled metabolite 111-In-DTPA-D-Phe in the lysosomes. This metabolite is not capable of passing the lysosomal and / or other cell membranes. Therefore, it stays in the lysosomes, causing the long retention time of 111-In in sst2 - positive cells.
- Planar imaging: 111 MBq (3,0 mCi) - IV.
- SPECT imaging: 222 MBq (6,0 mCi) - IV.
Transient adverse effects at a frequency of less than 1%:
- Changes in liver enzymes.
- Joint pain.
- One reported case of bradycardia and one case of decreased hematocrit and hemoglobin.
- The usual dose of 111-In-pentetreotide is approximately 5 - 20 times less than for octreotide (subtherapeutic). Adverse reactions which have been associated with octreotide in 3% - 10% of patients:
- Injection site pain.
- Abdominal pain / discomfort.
- Loose stools.
- Hyper- and hypo-glycemia.
- The sensitivity of scintigraphy with 111-In-pentetreotide may be reduced in patients concurrently receiving therapeutic doses of octreotide acetate (consideration should be given to temporarily suspending octreotide acetate therapy before the administration of 111-In-pentetreotide and to monitoring the patient for any signs of withdrawal).
- Therapy with octreotide acetate can produce severe hypoglycemia in patients with insulinomas. Since pentetreotide is an analog of octreotide, an intravenous line is recommended in any patient suspected of having an insulinoma. An intravenous solution containing glucose should be administered just before and during administration of 111-In-pentetreotide.
- Use of 111-In-pentetreotide in patients with impaired renal function should be carefully considered.
- To help reduce the radiation dose to the thyroid, kidneys, bladder and other target organs, patients should be well hydrated before the administration of 111-In-pentetreotide. Elimination of extra fluid intake will help reduce the radiation dose by flushing out unbound, labelled pentetreotide by glomerular filtration. Patients should increase fluid intake and void frequently for one day after administration of this drug. Moreover, it is recommended that patients be given a mild laxative before and after administration of 111-In-pentetreotide (starting the evening before the radioactive drug is administered and continuing for 48 hours). In patients with an insulinoma, bowel - cleansing should be undertaken only after consultation with an endocrinologist. Ample fluid intake is necessary during this period as a support both to renal elimination and the bowel - cleansing process.
- A single dose of 111-In-pentetreotide is not expected to cause cholelithiasis (octreotide acetate and somatostatin may be associated with cholelithiasis presumably by altering fat absorption and possibly by decreasing motility of the gallbladder.
- 111-In-pentetreotide should not be administered to a pregnant woman unless the potential benefit justifies the potential risk to the fetus.
- Because many drugs are excreted in human milk, caution should be exercised when 111-In-pentetreotide is administered to a nursing woman.
- 111-In-pentetreotide should not be administered in total parenteral nutrition solutions or through the same intravenous line (a complex glycosyl octreotide conjugate may form).