with time. The non-target tissue uptakes were very low. The significanttumor localization, good retention and high target/non-target ratios ofthe complex exhibited favorable properties, suggesting 99mTc-HYNIC-DG would be a promising candidate for tumor imaging.

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.042

37Copolymer based radiotracers for liver ASGP-R targetedSPECT imagingChang Liua,b, Zhide Guoa, Pu Zhanga,b, Xianzhong Zhanga

aCMITM, SKLVD, School of Public Health, Xiamen University, ChinabCollege of Chemistry, Beijing Normal University, China

Asialoglycoprotein receptor (ASGP-R) is a well-known cell surfacereceptor specific for liver, present in normal mammalian hepatocytemembrane. Detection of its number and activity is an excellent methodfor evaluating the status and function of liver [1]. Copolymer basedradiotracers with controllable ratio of targeting moiety (VLA) weredeveloped as potential ASGP-R targeted imaging agents. P(VLA-co-VNI)were synthesized by free-radical copolymerization and lyophilized for99mTc instant kit labeling with high yield and RCP (N99%) [2]. Static 3DSPECT/CT images were acquired at 1 h and 4 h after injection of 18 MBqseries of 99mTc-tracers in normalmice. The results showed that liver hasspecific high uptake at 1 h p.i. with good retention. (NSFC (21271030)and 973 Program of China (2014CB744503)).

References

[1] Yang WJ, et al. J Nucl Med 2011;52:978–85.[2] Liu C, et al. Nucl Med Biol 2014 [accepted].

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.122

38New GRPR-antagonists mimicking [99mTc]Demobesin 1T. Mainaa, A. Nikolopouloua, R. Cescatob, D. Charalambidisa,B. Waserb, E. Ketania, J.C. Reubib, B.A. Nocka

aNCSR “Demokritos”/GRNCSR “Demokritos”/GRbUniversity of Bern/CHUniversity of Bern/CH

We have previously reported on the GRPR-antagonist [99mTc]Demobesin 1, [99mTc]DB1 (99mTc-[N4′-dig-DPhe6,Leu-NHEt13]BBN(6–13)), which shows superior biological profile, and in particular a higheruptake in PC-3 xenografts inmice, than analogous agonist-based 99mTc-radioligands. We now present a small library of [99mTc]DB1 mimics byperforming strategic structural modifications in: a) the spacer ([99mTc]DB2, [99mTc]DB7 and [99mTc]DB8), b) the C-terminus ([99mTc]DB9 and[99mTc]DB10) and c) the peptide chain ([99mTc]DB11 and [99mTc]DB12).

The effects of these modifications were studied in PC-3 cells and mousemodels. All analogs showed sub-nM affinity for the human GRPR withDB8 and DB10 ranking first in affinity. Both analogs behaved as potentGRPR-antagonists during an immunofluorescence microscopy–basedreceptor internalization assay. During incubation in PC-3 cells (2 h/37 °C) all 99mTc-radiopeptides remained bound on the cell membrane,but [99mTc]DB8 displayed the highest uptake by the cells. In micebearing PC-3 tumors, all 99mTc-radiopeptides showed GRPR-specifictumor uptake and rapidly cleared from background tissues, includingthe GRPR-rich pancreas, via the kidneys into urine. [99mTc]DB8displayed the highest tumor uptake (28.8 ± 4.1% ID/g at 1 h pi). Mostimportantly, the tumor uptake remained impressively high even after24 h pi (16.3 ± 1.8% ID/g), well surpassing the tumor retention of thelead compound [99mTc]DB1 (5.4 ± 0.7% ID/g at 24 h pi).

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.066

39New [99mTc(CO)3(NSN)]+ chelate conjugated to a somatostatinreceptor-seeking peptideGeorge Makrisa, Lauren Radfordb, Fabio Gallazzib, Silvia Jurissonb,Heather Hennkensb, Dionysia Papagiannopouloua

aAristotle University of Thessaloniki, GreecebUniversity of MO-Columbia, USA

Chelating 99mTc to a somatostatin receptor (SSTR)-seekingpeptide may allow targeted delivery of this attractive diagnosticradionuclide to neuroendocrine cancers that over-express SSTRs. Wepresent here the synthesis of a novel tridentate bifunctional chelator,3-(2-aminoethylthio)-3-(1H-imidazol-4-yl)propanoic acid L, its pyr-rolidine amide derivative Lpyr, and the Lsst2-ANT bioconjugate,where the SSTR-seeking peptide sst2-ANT (4-NO2-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH2) is linked to L via the N-terminus. Thechelator L coordinates via the imidazole N, thioether S, and amine Ndonor atoms to yield cationic fac-[Tc/Re(CO)3(NSN)]+ type com-plexes. The complexes ReL, ReLpyr and ReLsst2-ANT were synthe-sized in high yield and were characterized spectroscopically. Thetracer complexes 99mTcL, 99mTcLpyr and 99mTcLsst2-ANT weresynthesized quantitatively, and their identities were confirmed byHPLC co-elution with their Re analogues. In vitro stability studies ofboth 99mTcL and 99mTcLpyr in histidine and cysteine showed that thecomplexes remained intact (N97%) after 24 h incubations. Furthermore,rat urine analysis of 99mTcLpyr showed that the radiocomplex wasexcreted intact after 4–6 h. Initial in vitro stability of 99mTcLsst2-ANT inhistidine and cysteine was also high (N90% intact over 24 h),demonstrating the potential of further evaluation of this newbioconjugate for targeting SSTR-rich neuroendocrine tumors.

http://dx.doi.org/10.1016/j.nucmedbio.2014.05.074

40Synthesis and biological evaluation of novel bone-seeking[Re/99mTc(CO)3] complexesGeorge Makrisa, Ioannis Pirmettisb, Minas S. Papadopoulosb,Dionysia Papagiannopouloua

aAristotle University of Thessaloniki, GreecebINRASTES, NCSR “Demokritos”, Greece

Radiolabelled bisphosphonates such us 99mTc-MDP and 186Re/188Re-ΗΕDP bind to bone matrix carrying γ or β radiation and are used forbone imaging or bone pain palliation, respectively. In our work we

Fig. 1. SPECT/CT images of 99mTc-p(VLA-co-VNI)(Tricine)(TPPTS) with different ratioof VLA:VNI in normal mice.

Abstracts 623