SSTR2 transduced animals showed a three- to fourfold increase in muscle uptake compared to controls. The increase in 68Ga-DOTATATE uptake was AAV dose dependent. Liver transduced animals showed a tendency for reduction in liver uptake over time whereas muscle transduced animals showed stable uptake levels for 6 months. Loss of expression in liver may be mediated by an autoimmune response, therefore AAV-TBG-SSTR2 was also injected into athymic nude mice. In these animals, 68Ga-DOTATATE uptake in liver is markedly higher than in controls, and there is no evidence in reduction of uptake in the three month observation period. Evaluation of gene transfer is feasible with the described approach and may be useful for quantitative monitoring of gene therapy in animal models. doi:10.1016/j.nucmedbio.2010.04.040 Imaging changes of p-glycoprotein activity in vivo with 68 Ga-Schiff base Marco Fellner a , Wolfgang Dillenburg b , Frank Rösch a , Oliver Thews b a COSTD38-WG3, Institute of Nuclear Chemistry, Mainz, Germany b Institute of Physiology and Pathophysiology, COSTD38-WG3, Mainz, Germany P-glycoprotein (pGP) pumps a wide number of xenobiotics out of the cell leading to multidrug resistance in many tumours. It was shown in vitro that pGP activity can be increased by extracellular acidosis. Here mitogen-activated protein kinases (MAPKs) (p38, ERK1/2) seem to play an important role. With the Schiff base complex 68 Ga-MFL6.MZ it became possible to visualize the activity of pGP in vivo by μ-positron emission tomography (PET). MFL6.MZ was labelled with 68 Ga. Animal studies were performed with tumour-bearing Copenhagen rats. Acidification was achieved by direct tumour injection of small amounts of lactic acid, respectively SB203580 (p38) and U0126 (ERK1/2) for MAPK inhibition. Acidifying the tumour reduces the tracer accumulation indicating a higher pGP activity (80% compared to control tumours). MAPK inhibitors reduced the pGP transport rate which resulted in a higher tracer accumulation. SB203580 (p38) led to doubling the tracer activity, whereas with U0126 (ERK1/2) the concentration increased by 30%. The PET tracer 68 Ga-MFL6.MZ indicates that pGP is markedly activated under acidic environment. The p38-MAPK pathway plays an important role for pGP regulation in vivo, whereas ERK1/2 is of minor importance. From these results new strategies for overcoming multidrug resistance (e.g., inhibition of p38) may be developed. doi:10.1016/j.nucmedbio.2010.04.147 Can PET hypoxia tracers predict radioresistance? Kazumi Chia ⁎ , Amanda J. Weeks, Rowena L. Paul, Marcel Cleij, Philip J. Blower King's College London, Division of Imaging Sciences, Rayne Institute, St. Thomas' Hospital, SE1 7EH London, UK In positron emission tomography (PET) hypoxia imaging, it is not clear whether the pO 2 at which cells “switch” from low to high tracer uptake match that at which they “switch” from radiation sensitive to resistant. The aim of this work is to define the relationship between hypoxia tracer uptake (Cu-64- labelled ATSM, ATS, ATSE, DTS, DTSE, DTSM, F-18-FMISO), radiosen- sitivity, pimonidazole, and HIF-1α at different pO 2 . All experiments were performed using the same hypoxia apparatus. Radiosensitivity was assessed by clonogenic assay and tracer uptake by gamma counting. Pimonidazole was measured by flow cytometry and HIF- 1α levels by Western blotting. Radiosensitivity started to decrease as pO 2 dropped below 25 mmHg. All tracers showed hypoxia-selective uptake at levels below 2 mmHg, except for CuDTSE where it increased at 6 mmHg. By contrast, pimonidazole uptake and HIF-1α expression plateaued at 8 mmHg. Pimonidazole uptake and HIF-1α expression matched radiosensitivity better than the PET tracers. Significant uptake of the PET tracers occurred only at extreme hypoxia, well below the pO 2 at which radiation resistance became significant. The results imply that a significant fraction of radioresistant cells will not take up tracer because they are not hypoxic enough. Thus the tracers are likely to underestimate radioresistance due to hypoxia. New tracers are needed whose uptake/pO 2 profile better matches the radioresistance profile in order to more accurately estimate the radioresistance due to hypoxia. doi:10.1016/j.nucmedbio.2010.04.109 64 Cu-galectin-3-specific peptide as an in vivo PET imaging agent i Susan L. Deutscher a,b , Senthil R. Kumar b , Thomas P. Quinn b a Research Division, Harry S. Truman Veterans Hospital, Columbia, MO 65201, USA b Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA Objectives: The purpose of our study was to evaluate a phage display identified galectin-3 (gal-3) avid peptide G3-C12 (ANTPCGPYTHDCPCKR) as a positron emission tomography (PET) imaging agent for gal-3 expressing breast tumors. Methods: The chelator CB-TE2A was attached to the N-terminus of G3-C12 for labeling with 64 Cu. Cell binding studies with human gal-3 positive MDA-MB- 435 breast carcinoma cells and normal mammary cells were performed. In vivo biodistribution and PET imaging were analyzed in SCID mice bearing MDA- MB-435 tumor xenografts. Results: 64 Cu-CB-TE2A- G3-C12 peptide bound to human breast carcinoma cells with an IC 50 of 130±10.2 nM. In vivo biodistribution studies demonstrated radiolabeled peptide accumulation in MDA-MB-435 tumor- bearing SCID mice (∼1.0% ID/g, at 2 h). Uptake of radiolabeled peptide in the liver, intestines and lungs was low at ∼0.97% ID/g, ∼0.36% ID/g and ~0.29% ID/g, respectively at 2 h, while kidney uptake was high N20% ID/g. PET imaging studies of 64 Cu-labeled CB-TE2A-peptide revealed good tumor uptake after 2 h post injection. Conclusions: Our results indicate that 64 Cu-CB-TE2A-G3-C12 can be developed as a PET radiotracer for gal-3 expressing tumors. doi:10.1016/j.nucmedbio.2010.04.054 A comparative study of 64 Cu-NO2A-Bombesin antagonist and agonist ligands Charles Jeffrey Smith a,b , Prasant K. Nanda a , Stephanie Lane a , Gary L. Sieckman b , Timothy J. Hoffman a,b , Tammy Rold b a University of Missouri-Columbia School of Medicine, Columbia, MO 65211, USA b Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA Gastrin-releasing peptide receptors (GRPr) are highly expressed on many types of human cancer cells including prostate cancer. Bombesin (BBN) is a 14-amino-acid peptide that binds the GRPr with very high affinity and specificity. The aim of this study is to develop new 64 Cu-labeled BBN analogs having high tumor uptake and optimal pharmacokinetics for specific targeting and molecular imaging of human prostate cancer. In this study, we describe the synthesis, characterization, and in vitro and in vivo studies of i Research support: National Institutes of Health grants P50CA103130-01 and 1R-21CA137239-01A1 and a Merit Review Award from the Veterans Administration. 725 Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726