TY - JOUR
T1 - In vitro and in vivo evaluation of copper-64-octreotide conjugates
AU - Anderson, C. J.
AU - Pajeau, T. S.
AU - Edwards, W. B.
AU - Sherman, E. L.C.
AU - Rogers, B. E.
AU - Welch, M. J.
PY - 1995
Y1 - 1995
N2 - Copper-64 (T( 1/2 ) = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. Octreotide, a somatostatin receptor ligand, has been conjugated with TETA and CPTA, labeled with 64Cu, evaluated both in vitro and in vivo and compared to 111In-DTPA-D-Phe1-octreotide. Methods: The carboxylic acid moieties on that bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the linking agents hydroxybenzotriazol (HOBT) and diisopropylcarbodiimide (DIC). Receptor binding assays on all three radiolabeled octreotide conjugates were accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo biodistribution was performed using normal Sprague-Dawley rats and Lewis rats carrying a somatostatin receptor-positive rat pancreatic tumor. Results: The binding affinities of 64Cu-CPTA-D- Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide in AtT20 cell membranes were both greater than 111In-DTPA-D-Phe1-octreotide (K(d), 78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1- octreotide was localized primarily in the liver. Copper-64-TETA-D-Phe1- octreotide, similar to 111In-DTPA-D-Phe1-octreotide, had moderate uptake in the kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948 pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64Cu- TETA-D-Phe1-octreotide had uptake in tumors comparable to or better than 111In-DTPA-D-Phe1-octreotide. Conclusion: Of the two 64Cu-labeled octreotide conjugates evaluated, 64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64-TETA-D-Phe1-octreotide binds to the somatostatin receptor with five times the affinity of 111In- octreotide, has desirable clearance properties (renal clearance with rapid excretion) and is a potential agent for PET imaging of somatostatin receptors.
AB - Copper-64 (T( 1/2 ) = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. Octreotide, a somatostatin receptor ligand, has been conjugated with TETA and CPTA, labeled with 64Cu, evaluated both in vitro and in vivo and compared to 111In-DTPA-D-Phe1-octreotide. Methods: The carboxylic acid moieties on that bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the linking agents hydroxybenzotriazol (HOBT) and diisopropylcarbodiimide (DIC). Receptor binding assays on all three radiolabeled octreotide conjugates were accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo biodistribution was performed using normal Sprague-Dawley rats and Lewis rats carrying a somatostatin receptor-positive rat pancreatic tumor. Results: The binding affinities of 64Cu-CPTA-D- Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide in AtT20 cell membranes were both greater than 111In-DTPA-D-Phe1-octreotide (K(d), 78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1- octreotide was localized primarily in the liver. Copper-64-TETA-D-Phe1- octreotide, similar to 111In-DTPA-D-Phe1-octreotide, had moderate uptake in the kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948 pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64Cu- TETA-D-Phe1-octreotide had uptake in tumors comparable to or better than 111In-DTPA-D-Phe1-octreotide. Conclusion: Of the two 64Cu-labeled octreotide conjugates evaluated, 64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64-TETA-D-Phe1-octreotide binds to the somatostatin receptor with five times the affinity of 111In- octreotide, has desirable clearance properties (renal clearance with rapid excretion) and is a potential agent for PET imaging of somatostatin receptors.
KW - DTPA
KW - copper-64-TETA octreotide
KW - indium-111-octreotide
KW - receptor binding
UR - http://www.scopus.com/inward/record.url?scp=0028805886&partnerID=8YFLogxK
M3 - Article
C2 - 8523125
AN - SCOPUS:0028805886
VL - 36
SP - 2315
EP - 2325
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 12
ER -