Abstract | UNLABELLED: Recently, the somatostatin receptor subtype 2 (SSTR2) selective antagonist sst2-ANT was determined to have a high affinity for SSTR2. Additionally, 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-sst2-ANT showed high uptake in an SSTR2-transfected, tumor-bearing mouse model and suggested that radiolabeled SSTR2 antagonists may be superior to agonists for imaging SSTR2-positive tumors. This report describes the synthesis and evaluation of 64Cu-CB-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2] hexadecane-sst2-ANT (64Cu-CB-TE2A-sst2-ANT) as a PET radiopharmaceutical for the in vivo imaging of SSTR2-positive tumors. METHODS: RESULTS: The dissociation constant value for the radiopharmaceutical was determined to be 26 +/- 2.4 nM, and the maximum number of binding sites was 23,000 fmol/mg. 64Cu-CB-TE2A-sst2-ANT showed significantly less internalization than did 64Cu-CB-TE2A-Y3-TATE at time points from 15 min to 4 h. Biodistribution studies revealed that the clearance of 64Cu-CB-TE2A-sst2-ANT from the blood was rapid, whereas the clearance of 64Cu-CB-TE2A-sst2-ANT from the liver and kidneys was more modest at all time points. Tumor-to-blood and tumor-to-muscle ratios were determined to be better for 64Cu-CB-TE2A-sst2-ANT than those for 64Cu-CB-TE2A-Y3-TATE at the later time points, although liver and kidney uptake was significantly higher. Small-animal imaging using 64Cu-CB-TE2A-sst2-ANT revealed excellent tumor-to-background contrast at 4 h after injection, and standardized uptake values remained high even after 24 h. CONCLUSION:
|
Authors | Thaddeus J Wadas, Martin Eiblmaier, Alexander Zheleznyak, Christopher D Sherman, Riccardo Ferdani, Kexian Liang, Samuel Achilefu, Carolyn J Anderson |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 49
Issue 11
Pg. 1819-27
(Nov 2008)
ISSN: 0161-5505 [Print] United States |
PMID | 18927338
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- (4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)copper(II)
- Organometallic Compounds
- Peptides
- Radiopharmaceuticals
- Receptors, Somatostatin
- somatostatin receptor 2
|
Topics |
- Amino Acid Sequence
- Animals
- Cell Line, Tumor
- Male
- Neoplasms
(diagnostic imaging, metabolism)
- Organometallic Compounds
(chemistry)
- Peptides
(chemistry, metabolism, pharmacokinetics)
- Positron-Emission Tomography
- Radiochemistry
- Radiopharmaceuticals
(chemistry)
- Rats
- Receptors, Somatostatin
(antagonists & inhibitors, metabolism)
- Tissue Distribution
|