RT Journal Article
SR Electronic
T1 Comparison of agonist/antagonist versions of a synthetic tracer for human bradykinin B1 receptor imaging using positron emission tomography
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 441
OP 441
VO 55
IS supplement 1
A1 Amouroux, Guillaume
A1 Zhang, Zhengxing
A1 Pan, Jinhe
A1 Jenni, Silvia
A1 Hundal-Jabal, Navjit
A1 Benard, Francois
A1 Lin, Kuo-Shyan
YR 2014
UL http://jnm.snmjournals.org/content/55/supplement_1/441.abstract
AB 441 Objectives Human Bradykinin (BK) B1 receptor (hB1R), a G protein-coupled receptor that is overexpressed in many cancers as well as acutely damaged tissues. B1R is not expressed under healthy conditions, hence making it a promising marker for cancer targeting. The goal of this study was to evaluate whether there is a difference between the tumor uptake of hB1R agonist and antagonist. Methods We compared the hB1R agonist 68Ga-DOTA-Ahx-Lys-[Hyp3,Cha5,D-Phe8,desArg9]BK (Z01115) with the antagonist 68Ga-DOTA-Ahx-Lys-[Hyp3,Cha5,Leu8,desArg9]BK (SH01078). Binding affinity was measured by competitive binding assays using CHO:hB1R cell membrane. 68Ga labeling was performed in NaOAc buffer (pH 4.1) with microwave heating for 1 min. PET imaging and biodistribution studies were performed in NSG mice bearing wild-type (HEK293T) and transfected (HEK293T:hB1R) tumors. Results Z01115 and SH01078 bound hB1R with high affinity (Ki (nM): 27.8 ± 4.9 (SH01078), 25.4 ± 5.1 (Z01115)). [68Ga]Z01115 and [68Ga]SH01078 were obtained in high radiochemical yield (>70%) and purity (>99%). Both tracers were stable in mouse plasma with negligible degradation after 1h incubation. PET imaging and biodistribution studies showed rapid clearance of the radioactivity from blood and normal tissues, and excretion via the renal pathway. At 1h p.i., only kidneys, bladder and the hB1R positive HEK293T:hB1R tumor were visualized on PET images. Average uptake ratios of HEK293T:hB1R to HEK293T tumor, blood and muscle at 1h p.i. were higher for the agonist [68Ga]Z01115 (29.4, 86.4, 86.2, respectively) compared to the antagonist [68Ga]SH01078 (6.8, 20.6, 11.2). Conclusions [68Ga]Z01115 and [68Ga]SH01078 generated specific, high contrast images of hB1R positive tumors xenografted in mice. Our results showed that in this experimental model, the agonist provided superior contrast to visualize hB1R-expressing lesions.