Introduction Positron emission tomography (PET) is suggested for early monitoring of treatment response, assuming that effective anticancer treatment induces metabolic changes that precede morphology alterations and changes in growth. The aim of this study was to introduce multicellular tumour spheroids (MTS) to study the effect of anticancer drugs and suggest an appropriate PET tracer for further studies.

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Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR‐2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti‐angiogenic drugs target VEGF/VEGFR‐2 signaling and induce changes in VEGFR‐2 prevalence. To monitor VEGFR‐2 prevalence in the course of treatment, we are evaluating 68Ga positron emission tomography imaging agents based on macrocyclic chelators, site‐specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR‐2 ligand, single‐chain (sc) VEGF. The 68Ga‐labeling was performed at room temperature with NOTA (2,2′,2′′‐(1,4,7‐triazonane‐1,4,7‐triyl) triacetic acid) conjugates or at 90 °C by using either conventional or microwave heating with NOTA and DOTA (2,2′,2′′,2′′′‐(1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayl) tetraacetic acid) conjugates. The fastest (~2 min) and the highest incorporation (>90%) of 68Ga into conjugate that resulted in the highest specific radioactivity (~400 MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA‐ and DOTA‐containing tracers was validated in 3‐D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR‐2. The NOTA‐containing tracer also displayed a rapid accumulation (~ 20 s after intravenous injection) to steady‐state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF‐PEG‐[68 Ga]NOTA and scVEGF‐PEG‐[68 Ga]DOTA might be promising tracers for monitoring VEGFR‐2 prevalence and should be further explored. Copyright © 2011 John Wiley & Sons, Ltd.

Background: In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality.

Three11 C-radiolabelled high-affinity nonpeptide AT 2 receptor-selective ligands were synthesized and one of these was evaluated as positron emission tomography (PET) tracer. The labelling reaction was performed via palladium(0)-mediated aminocarbonylation of the aryl iodide substrate using [11 C]carbon monoxide as the labelled precursor. As an example, starting with 10.0 GBq [ 11 C]carbon monoxide, 1.10 GBq of the product11 C]4d was obtained in 36% decay-corrected radiochemical yield (from [ 11 C]carbon monoxide), 42 min from end of bombardment with a specific activity of 110 GBq Á lmol À1. The N-isopropyl-11 C]4c (radiochemical purity 495%) was studied employing autoradiography, organ distribution, and small animal PET. In vitro autoradiography showed specific binding in the pancreas and kidney. Organ distribution in six rats revealed a high uptake in the liver, intestine, kidney, and adrenals. Small animal PET showed rapid and reversible uptake in the kidneys followed by accumulation in the urinary bladder suggesting fast renal excretion of the tracer. In addition, high accumulation was also seen in the liver. For future studies, more metabolically stable tracers will need to be developed. To the best of our knowledge, this is the first attempt of the use of PET imaging for the detection of expressed, fully functional AT 2 receptors in living subjects.