Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling.
View Article and Find Full Text PDFThe purpose of this pictorial review is to describe emerging clinical applications of positron emission tomography (PET)/magnetic resonance imaging (MRI), the newest clinical hybrid imaging modality, with a specific focus on abdominal and pelvic malignancies. Important issues regarding the clinical implementation of PET/MRI systems, including workflow considerations and protocol development, are examined. The unique technical challenges of simultaneous PET/MRI acquisition and MRI-based attenuation correction are also briefly discussed.
View Article and Find Full Text PDFThe purpose of this article is to introduce the underlying challenges associated with the incorporation of magnetic resonance imaging (MRI) into the new hybrid imaging modality simultaneous positron emission tomography (PET)/MR and their impact on attenuation correction, sequence optimization, and protocol development. Many adjustments to MR sequences are necessary for optimal whole-body and fused image results.
View Article and Find Full Text PDFThe nortropane cocaine analogue, 2beta-carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]nortropane (ZIENT), is a high affinity, selective serotonin transporter (SERT) ligand that has shown promise as a SERT imaging agent for single photon computed tomography (SPECT) when labeled with I-123. Synthesis of the labeling precursor, radiosynthesis of [(11)C]ZIENT, and in vivo evaluation in anesthetized and awake monkeys have been performed to determine the suitability of [(11)C]ZIENT as a PET agent for SERT imaging.
View Article and Find Full Text PDF2beta-Carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane (ZIENT) (6) and 2beta-carbomethoxy-3beta-(4'-((E)-2-iodoethenyl)phenyl)nortropane (EIENT) (10) were prepared and evaluated in vitro and in vivo for serotonin transporter (SERT) selectivity and specificity. High specific activity [(123)I]ZIENT and [(123)I]EIENT were synthesized in 45% (n = 5) and 42% (n = 4) radiochemical yield (decay-corrected to end of bombardment (EOB)), respectively, by preparation of the precursor carbomethoxy-3beta-(4'-((Z)-2-trimethylstannylethenyl)phenyl)nortropane (7) and 2beta-carbomethoxy-3beta-(4'-((E)-2-tributylstannylethenyl)phenyl)nortropane (9), respectively, followed by treatment with no carrier-added sodium [(123)I]iodide and hydrogen peroxide in ethanolic HCl. Competition binding in cells stably expressing the transfected human SERT, dopamine transporter (DAT), and norepinephrine transporter (NET) using [(3)H]citalopram, [(3)H]WIN 35,428, and [(3)H]nisoxetine, respectively, demonstrated the following order of SERT affinity (K(i) in nM): ZIENT (0.
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