Cyclic minigastrin analogues for gastrin receptor scintigraphy with technetium-99m: preclinical evaluation.
Two cyclized minigastrin analogues for gastrin receptor scintigraphy were synthesized and derivatized with HYNIC at the N-terminus for labeling with 99mTc. Radiolabeling efficiency, stability, cell internalization, and receptor binding on CCK-2 receptor expressing AR42J cells were studied and the biodistribution evaluated in tumor bearing nude mice, including NanoSPECT/CT imaging. Metabolites in urine, liver, and kidneys were analyzed by radio-HPLC. Radiolabeled cyclic MG showed high stability in vitro and receptor mediated uptake in AR42J cells. In the animal tumor model, fast renal clearance and low nonspecific uptake in most organs were observed. A tumor uptake >3% was calculated ex vivo 1 h p.i. for both 99mTc-EDDA-HYNIC-cyclo-MG1 and 99mTc-EDDA-HYNIC-cyclo-MG2. In an imaging study with 99mTc-EDDA-HYNIC-cyclo-MG1, the tumor was clearly visualized. The metabolite analysis indicated rapid enzymatic degradation in vivo.
von Guggenberg
Elisabeth
E
Department of Nuclear Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. elisabeth.vonguggenberg@uki.at
Sallegger
Werner
W
Helbok
Anna
A
Ocak
Meltem
M
King
Robert
R
Mather
Stephen J
SJ
Decristoforo
Clemens
C
D000595:Amino Acid Sequence; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D005755:Gastrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D043887:Receptor, Cholecystokinin B / Q000032:analysis*; D013667:Technetium; D014018:Tissue Distribution
D005755:Gastrins; D019275:Radiopharmaceuticals; D043887:Receptor, Cholecystokinin B; C008530:minigastrin; D013667:Technetium