In vitro modeling of the clinical interactions between octreotide and 111In-pentetreotide: is there evidence of somatostatin receptor downregulation?
Some authors have suggested that chronic octreotide use enhances the efficiency of radiolabeled somatostatin receptor (sst) imaging. Conversely, desensitization of sst on tumor tissue (tachyphylaxis) may occur occasionally in patients on chronic octreotide therapy. Assuming that chronic exposure to octreotide induces tachyphylaxis, we hypothesized that chronic exposure of sst subtype 2 (sst2)-expressing cells to octreotide would downregulate binding of 111In-pentetreotide to sst and that this downregulation would be due to a reduction in the gene copy number for sst2.


METHODS
The clinical scenarios of acute (24 h) and chronic (2 wk) octreotide use, followed by either nuclear imaging exposure (8.6 pmol/L) or therapeutic exposure (510 pmol/L) to (111)In-pentetreotide, were modeled in vitro. Receptor binding in IMR-32 human neuroblastoma cells (high sst2 expression) and PANC-1 human pancreatic cancer cells (no detectable sst2 expression) was evaluated. Gene copy numbers for sst subtypes 1-5 in IMR-32 cells were determined by quantitative polymerase chain reaction.


RESULTS
Acute or chronic octreotide exposure at low or high doses did not significantly alter sst2 gene copy numbers or binding of either the diagnostic dose or the therapeutic dose of 111In-pentetreotide.


CONCLUSIONS
In vitro exposure of cells to low or high doses of octreotide for 1-14 d does not result in the development of either tachyphylaxis or upregulation of sst as assessed by changes in gene expression or in high-affinity binding.
Gunn
Susan H
SH
Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Schwimer
Joshua E
JE
Cox
Mary
M
Anthony
Catherine T
CT
O'Dorisio
Mary Sue
MS
Woltering
Eugene A
EA
D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism
D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; C081788:pentetreotide; D015282:Octreotide