Abstract
The radiolabeling of the natural octapeptide CCK8, derivatized with a cysteine residue (Cys-Gly-CCK8). by using the metal fragment [99mTc(N)(pNp3)]2+ (PNP3 = N,N-bis(dimethoxypropylphosphinoethyl)methoxyethylaniine) is reported. The [99mTc(N)(NS-Cys-Gly-CCK8)(PNP3)]+ complex was obtained according to two methods (one-step or two-step procedure) that gave the desired compound in high yield. The complex is stable In aqueous solution and in phosphate buffer. In vitro challenge experiments with an excess of cysteine and glutathione indicate that no transchelation reactions occur, confirming the high thermodynamic stability and kinetic inertness of this compound. Stability studies carried out in human and mouse serum, as well as in mouse liver homogenates, show that the radiolabeled compound remains intact for prolonged incubation at 37°C. Binding properties give Kd (19.0 ± 4.6 nmol/1) and Bmax (∼106 sites/cell) values in A431 cells overexpressing the CCK2-R. In vivo evaluation of the compound shows rapid and specific targeting to CCK2-R, a fourfold higher accumulation compared to nonreceptor expressing tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 211-219 |
| Number of pages | 9 |
| Journal | Journal of Peptide Science |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2007 |
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Keywords
- CCK8 peptide conjugate
- Nuclear medicine
- Tc-nitrido complexes
- Technetium
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
Cite this
The (Tc(N)(PNP))2+ metal fragment labeled cholecystokinin-8 (CCK8) peptide for CCK-2 receptors imaging : In vitro and in vivo studies. / Agostini, Stefania; Bolzati, Cristina; Didonè, Eliana; Cavazza-Ceccato, Mario; Refosco, Fiorenzo; Aloj, Luigi; Arra, Claudio; Aurilio, Michela; Tornesello, Anna Lucia; Tesauro, Diego; Morelli, Giancarlo.
In: Journal of Peptide Science, Vol. 13, No. 4, 04.2007, p. 211-219.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The (Tc(N)(PNP))2+ metal fragment labeled cholecystokinin-8 (CCK8) peptide for CCK-2 receptors imaging
T2 - In vitro and in vivo studies
AU - Agostini, Stefania
AU - Bolzati, Cristina
AU - Didonè, Eliana
AU - Cavazza-Ceccato, Mario
AU - Refosco, Fiorenzo
AU - Aloj, Luigi
AU - Arra, Claudio
AU - Aurilio, Michela
AU - Tornesello, Anna Lucia
AU - Tesauro, Diego
AU - Morelli, Giancarlo
PY - 2007/4
Y1 - 2007/4
N2 - The radiolabeling of the natural octapeptide CCK8, derivatized with a cysteine residue (Cys-Gly-CCK8). by using the metal fragment [99mTc(N)(pNp3)]2+ (PNP3 = N,N-bis(dimethoxypropylphosphinoethyl)methoxyethylaniine) is reported. The [99mTc(N)(NS-Cys-Gly-CCK8)(PNP3)]+ complex was obtained according to two methods (one-step or two-step procedure) that gave the desired compound in high yield. The complex is stable In aqueous solution and in phosphate buffer. In vitro challenge experiments with an excess of cysteine and glutathione indicate that no transchelation reactions occur, confirming the high thermodynamic stability and kinetic inertness of this compound. Stability studies carried out in human and mouse serum, as well as in mouse liver homogenates, show that the radiolabeled compound remains intact for prolonged incubation at 37°C. Binding properties give Kd (19.0 ± 4.6 nmol/1) and Bmax (∼106 sites/cell) values in A431 cells overexpressing the CCK2-R. In vivo evaluation of the compound shows rapid and specific targeting to CCK2-R, a fourfold higher accumulation compared to nonreceptor expressing tumors.
AB - The radiolabeling of the natural octapeptide CCK8, derivatized with a cysteine residue (Cys-Gly-CCK8). by using the metal fragment [99mTc(N)(pNp3)]2+ (PNP3 = N,N-bis(dimethoxypropylphosphinoethyl)methoxyethylaniine) is reported. The [99mTc(N)(NS-Cys-Gly-CCK8)(PNP3)]+ complex was obtained according to two methods (one-step or two-step procedure) that gave the desired compound in high yield. The complex is stable In aqueous solution and in phosphate buffer. In vitro challenge experiments with an excess of cysteine and glutathione indicate that no transchelation reactions occur, confirming the high thermodynamic stability and kinetic inertness of this compound. Stability studies carried out in human and mouse serum, as well as in mouse liver homogenates, show that the radiolabeled compound remains intact for prolonged incubation at 37°C. Binding properties give Kd (19.0 ± 4.6 nmol/1) and Bmax (∼106 sites/cell) values in A431 cells overexpressing the CCK2-R. In vivo evaluation of the compound shows rapid and specific targeting to CCK2-R, a fourfold higher accumulation compared to nonreceptor expressing tumors.
KW - CCK8 peptide conjugate
KW - Nuclear medicine
KW - Tc-nitrido complexes
KW - Technetium
UR - http://www.scopus.com/inward/record.url?scp=34247348172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247348172&partnerID=8YFLogxK
U2 - 10.1002/psc.834
DO - 10.1002/psc.834
M3 - Article
C2 - 17269133
AN - SCOPUS:34247348172
VL - 13
SP - 211
EP - 219
JO - Journal of Peptide Science
JF - Journal of Peptide Science
SN - 1075-2617
IS - 4
ER -