Evaluation of [99mTc-(CO)3-X-Y-Bombesin(7-14)NH2] conjugates for targeting gastrin-releasing peptide receptors overexpressed on breast carcinoma.
BACKGROUND
Gastrin-releasing peptide (GRP) receptors are overexpressed on a variety of human carcinomas, including those of the breast. These receptors may be targeted with bombesin (BBN), which binds to GRP receptors with high affinity and specificity. The aim of this study was to develop a (99m)Tc(I)-BBN analog with favorable pharmacokinetic properties in order to improve the visualization of breast cancer tissue.


METHODS
Solid-phase peptide synthesis was used to produce a series of X-Y-BBN-NH2 conjugates, where X is pyrazolyl (PZ1) or 2,3-diaminopropionic acid (DPR) and Y is a spacer sequence. Their metallated counterparts were prepared by reacting [(99m)Tc-(H(2)O)(3)(CO)(3)](+) with the corresponding ligand.


RESULTS
While the PZ1 conjugates exhibited higher GRP receptor binding affinities in vitro, the DPR analogs demonstrated superior target tissue accumulation and pharmacokinetic properties in vivo.


CONCLUSIONS
These results demonstrate the ability of the DPR derivatives (Y=glycylserylglycine, triserine) to clearly identify the T47-D tumor tissue in xenografted SCID mice.
Retzloff
Lauren B
LB
Radiopharmaceutical Sciences Institute, 143 Major Hall, University of Missouri, Columbia, MO 65211, USA.
Heinzke
Laura
L
Figureoa
Said D
SD
Sublett
Samantha V
SV
Ma
Lixin
L
Sieckman
Gary L
GL
Rold
Tammy L
TL
Santos
Isabel
I
Hoffman
Timothy J
TJ
Smith
Charles J
CJ
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics
D015609:Organotechnetium Compounds; D011720:Pyrazoles; D019275:Radiopharmaceuticals; D015091:beta-Alanine; D019886:Gastrin-Releasing Peptide; C011757:2,3-diaminopropionic acid; D001839:Bombesin