RT Journal Article SR Electronic T1 CCK-2/Gastrin Receptor–Targeted Tumor Imaging with 99mTc-Labeled Minigastrin Analogs JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1727 OP 1736 VO 46 IS 10 A1 Berthold A. Nock A1 Theodosia Maina A1 Martin Béhé A1 Anastasia Nikolopoulou A1 Martin Gotthardt A1 Jörg S. Schmitt A1 Thomas M. Behr A1 Helmut R. Mäcke YR 2005 UL http://jnm.snmjournals.org/content/46/10/1727.abstract AB The aim of this study was to evaluate 3 new 99mTc-labeled minigastrin analogs modified with open chain tetraamines at the N-terminus for their suitability in the CCK-2/gastrin-R–targeted imaging of tumors (CCK-2/gastrin-R = cholecystokinin subtype 2/gastrin receptor). Methods: The [(D)Glu1]minigastrin sequence was assembled on the solid support and the respective tetraamine precursors coupled at the N-terminus. Purified peptide conjugates were labeled with 99mTc under alkaline conditions. Saturation binding experiments were performed for (radio)metallated peptides [99mTc/99gTc]Demogastrin 1–3 in rat acinar pancreatic AR4-2J cell membranes. Internalization was studied in AR4-2J cells at 37°C. Radiopeptide stability was tested in murine plasma, urine, and kidney homogenates. Tissue distribution of the peptides was compared in healthy mice and athymic mice bearing AR4-2J tumors. Results: Peptide conjugates were obtained in 10%–30% overall yields by solid-phase techniques. Radiolabeling afforded >98% pure [99mTc]Demogastrin 1–3 species in specific activities of ∼37 GBq/μmol. Radiopeptides retained a high affinity for the CCK-2/gastrin-R in vitro (50% inhibitory concentration values of ∼1 nmol/L) and internalized rapidly in CCK-2/gastrin-R–positive cells. After injection in mice they displayed rapid, high, and specific localization in the CCK-2/gastrin-R–expressing tissues (stomach and AR4-2J tumor) and were excreted from the body via the kidneys in the form of hydrophilic metabolites. Conclusion: The promising characteristics of [99mTc]Demogastrin 1–3 both in vitro and in animal models illustrate their suitability for CCK-2/gastrin-R–targeted tumor imaging. These qualities could be confirmed for [99mTc]Demogastrin 2, which provided excellent delineation of tumor deposits in a first patient with metastatic medullary thyroid cancer.