A new automated method for quantification of left ventricular function from gated-single photon emission computed tomography (SPECT) images has been developed. The method for quantification of cardiac function (CAFU) is based on a heart shaped model and the active shape algorithm. The model contains statistical information of the variability of left ventricular shape. CAFU was adjusted based on the results from the analysis of five simulated gated-SPECT studies with well defined volumes of the left ventricle. The digital phantom NURBS-based Cardiac-Torso (NCAT) and the Monte-Carlo method SIMIND were used to simulate the studies. Finally CAFU was validated on ten rest studies from patients referred for routine stress/rest myocardial perfusion scintigraphy and compared with Cedar-Sinai quantitative gated-SPECT (QGS), a commercially available program for quantification of gated-SPECT images. The maximal differences between the CAFU estimations and the true left ventricular volumes of the digital phantoms were 11 ml for the end-diastolic volume (EDV), 3 ml for the end-systolic volume (ESV) and 3% for the ejection fraction (EF). The largest differences were seen in the smallest heart. In the patient group the EDV calculated using QGS and CAFU showed good agreement for large hearts and higher CAFU values compared with QGS for the smaller hearts. In the larger hearts, ESV was much larger for QGS than for CAFU both in the phantom and patient studies. In the smallest hearts there was good agreement between QGS and CAFU. The findings of this study indicate that our new automated method for quantification of gated-SPECT images can accurately measure left ventricular volumes and EF.

(68)Ga-NODAGA-E[c(RGDyK)](2) and (64)Cu-NODAGA-E[c(RGDyK)](2) can be easily synthesized and are both promising candidates for PET imaging of integrin αVβ3 positive tumor cells. (68)Ga-NODAGA-E[c(RGDyK)](2) showed slightly more stable tumor retention. With the advantage of in-house commercially (68)Ge/(68)Ga generators, (68)Ga-NODAGA-E[c(RGDyK)](2) may be the best choice for future clinical PET imaging in humans.

Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of (64)Cu-DOTA-AE105.

Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF. The purpose of this study was to investigate the possibility of using active siteinhibited FVII (FVIIai) labeled with 64 Cu for PET imaging of TF expression. Methods: FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCNBn-NOTA) and labeled with 64 Cu ( 64 Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of 64 Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with 64 Cu-NOTAFVIIai was investigated in subcutaneous pancreatic tumor models with different levels of TF expression and in a competition experiment. In addition, imaging of orthotopic pancreatic tumors was performed using 64 Cu-NOTA-FVIIai and PET/MRI. In vivo imaging data were supported by ex vivo biodistribution, flow cytometry, and immunohistochemistry. Results: Longitudinal PET imaging with 64 Cu-NOTA-FVIIai showed a tumor uptake of 2.3 ± 0.2, 3.7 ± 0.3, 3.4 ± 0.3, and 2.4 ± 0.3 percentage injected dose per gram at 1, 4, 15, and 36 h after injection, respectively. An increase in tumor-tonormal-tissue contrast was observed over the imaging time course. Competition with unlabeled FVIIai significantly (P , 0.001) reduced the tumor uptake. The tumor uptake observed in models with different TF expression levels was significantly different from each other (P , 0.001) and was in agreement with the TF level evaluated by TF immunohistochemistry staining. Orthotopic tumors were clearly visible on the PET/MR images, and the uptake of 64 Cu-NOTA-FVIIai was colocalized with viable tumor tissue. Conclusion: 64 Cu-NOTA-FVIIai is well suited for PET imaging of tumor TF expression, and imaging is capable of distinguishing the TF expression level of various pancreatic tumor models. Ti ssue factor (TF) is a 47-kDa glycosylated transmembrane protein consisting of a large extracellular domain and a short cytoplasmic domain. TF acts as the initiator of the extrinsic coagulation cascade. The zymogen factor VII (FVII) is the natural ligand to TF and gets activated to FVIIa on binding to TF. The TF-FVIIa complex further activates factor IX and factor X, eventually leading to fibrin deposition, platelet aggregation, and formation of a thrombus (1).In addition to its role in the coagulation cascade, TF is associated with cancer (1-3). TF expression has been found in all solid tumors, and its expression has been linked to mutation of the K-ras oncogene, loss...