Evaluation of [99mTc-(CO)3-X-Y-Bombesin(7-14)NH2] Conjugates for Targeting Gastrin-releasing Peptide Receptors Overexpressed on Breast Carcinoma

• Published in: Anticancer research Vol. 30; no. 1; pp. 19 - 30
• Main Authors: RETZLOFF, Lauren B, HEINZKE, Laura, FIGUREOA, Said D, SUBLETT, Samantha V, LIXIN MA, SIECKMAN, Gary L, ROLD, Tammy L, SANTOS, Isabel, HOFFMAN, Timothy J, SMITH, Charles J
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-01-2010
• Subjects: Animals; beta-Alanine - analogs & derivatives; beta-Alanine - chemical synthesis; beta-Alanine - pharmacokinetics; Biological and medical sciences; Bombesin - analogs & derivatives; Bombesin - chemical synthesis; Bombesin - pharmacokinetics; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - metabolism; Cell Line, Tumor; Drug Delivery Systems; Female; Gastrin-Releasing Peptide - metabolism; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Mice; Mice, Inbred ICR; Mice, SCID; Organotechnetium Compounds - chemical synthesis; Organotechnetium Compounds - pharmacokinetics; Pyrazoles - chemical synthesis; Pyrazoles - pharmacokinetics; Radionuclide Imaging; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Tissue Distribution; Tumors; GRP receptor; Breast disease; Bombesin; Targeting; technetium; Peptide hormone; Gene overexpression; Breast cancer; Malignant tumor; Neuropeptide; Gastrin releasing peptide; Mammary gland diseases; Breast carcinoma; carbonyl; Cancerology; Technetium 99mTc; T47-D; Hormone releasing factor; MDA-MB-231; Cancer; Biological receptor
• ISSN: 0250-7005; 1791-7530

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.
Materials and 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. Conclusion: These
results demonstrate the ability of the DPR derivatives (Y=glycylserylglycine, triserine) to clearly identify the T47-D tumor
tissue in xenografted SCID mice.