Bombe
sin i
s a tetradecapeptide neurohormone that bind
s to ga
strin-relea
sing peptide receptor
s (GRPR). GRPR
shave been found in a variet
y of cancer
s including inva
sive brea
st and pro
state tumor
s. The peptide MP2346(DOTA-(Pro
1,T
yr
4)-bombe
sin(1-14)) wa
s de
signed to bind to the
se GRP receptor
s. Thi
s stud
y wa
s undertakento evaluate radiolabeled MP2346 a
s a po
sitron emi
ssion tomograph
y (PET) imaging agent. MP2346 wa
sradiolabeled, in high radiochemical purit
y, with the po
sitron-emitting nuclide
s 64Cu (
t1/2 = 12.7 h,
s/gifchar
s/beta2.gif" BORDER=0 ALIGN="middle">
+ = 19.3%,
Eavg = 278 keV) and
86Y (
t1/2 = 14.7 h,
s/gifchar
s/beta2.gif" BORDER=0 ALIGN="middle">
+ = 33%,
Eavg = 664 keV).
64Cu-MP2346 and
86Y-MP2346 were
studied
in vitro for cellular internalization b
y GRPR-expre
ssing PC-3 (human pro
state adenocarcinoma) cell
s.Both
64Cu- and
86Y-MP2346 were
studied
in vivo for ti
ssue di
stribution in nude mice with PC-3 tumor
s. Biodi
stribution in PC3 tumor-bearing mice demon
strated higher tumor uptake, but lower liver retention, in animal
sinjected with
86Y-MP2346 compared to
64Cu-MP2346. Receptor-mediated uptake wa
s confirmed b
y a
significantreduction in uptake in the PC-3 tumor and other receptor-rich ti
ssue
s b
y coinjection of a blockade. Small animalPET/CT imaging wa
s carried out in mice bearing PC-3 tumor
s and rat
s bearing AR42J tumor
s. It wa
s po
ssibleto delineate PC-3 tumor
s in vivo with
64Cu-MP2346, but
superior
86Y-MP2346-PET image
s were obtained dueto lower uptake in clearance organ
s and lower background activit
y. The
86Y analogue demon
strated excellentPET image qualit
y in model
s of pro
state cancer for the delineation of the GRPR-rich tumor
s and warrant
s furtherinve
stigation.