99mTc targeting of Sst2-expressing tumors by tetraamineoctreotide: first results in CA20948 cells and rat models.
BACKGROUND
Somatostatin subtype 2 receptor (sst2)-targeted tumor imaging with [(111)In-DTPA0]octreotide is an established method for scintigraphic detection of neuroendocrine tumors. [99mTc]Demotide ([99mTc-N4-bzdg0, Tyr3]octreotide), presented herein, is a potential sst2-targeting radiotracer based on 99mTc.


METHODS
Demotide was synthesized in solution and labelled with 99mTc in alkaline medium. The in vitro properties of Demotide and [99mTc]Demotide were tested in sst2-expressing CA20948 cells and rat tissues, while biodistribution was studied in Lewis rats bearing CA20948 tumors.


RESULTS
During labelling, [99mTc]Demotide was obtained in >98% yields and typical 1 mCi/nmol specific activities. Demotide showed in vitro sub-nM affinity for the sst2. While rapidly internalizing into CA20948 cells, [99mTc]Demotide localized effectively in CA20948 implants (2.2 +/- 1.1% ID/g at 1 h post injection) and in target organs in rats via a sst-mediated process and cleared rapidly via the kidneys.


CONCLUSIONS
The above favorable characteristics validate [99mTc]Demotide as a promising 99mTc-radiotracer for the targeted-imaging of sst2-positive tumors.
Institute of Radioisotopes-Radiodiagnostic Products, National Center for Scientific Research Demokritos, 153 10 Athens, Greece.
Anastasia
A
Nikolopoulou
Berthold A
BA
Nock
Theodosia
T
Maina
D000818:Animals; D001667:Binding, Competitive; D004347:Drug Interactions; D007553:Isotope Labeling; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000096:biosynthesis* / Q000378:metabolism; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
C508291:99mTc-demotide; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C045210:3-Tyr-octreotide; D013667:Technetium; C093733:somatostatin receptor 2; D015282:Octreotide