Glucose and glutamine are the two principal nutrients that cancer cells use to proliferate and survive. Many cancers show altered glucose metabolism, which constitutes the basis for in vivo positron emission tomography (PET) imaging with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). However, ¹⁸F-FDG is ineffective in evaluating gliomas because of high background uptake in the brain. Glutamine metabolism is also altered in many cancers, and we demonstrate that PET imaging in vivo with the glutamine analog 4-¹⁸F-(2S,4R)-fluoroglutamine (¹⁸F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced ¹⁸F-FGln tumor avidity, corresponding with decreased tumor burden. ¹⁸F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where ¹⁸F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that ¹⁸F-FGln is avidly taken up by gliomas, can be used to assess metabolic nutrient uptake in gliomas in vivo, and may serve as a valuable tool in the clinical management of gliomas.

Introduction: Heat shock protein 90 (HSP90) serves as a critical facilitator for oncogene addiction. There has been augmenting enthusiasm in pursuing HSP90 as an anticancer strategy. In fact, since...

Preclinical and trial data support fluorine 18–(2S,4R)-4-fluoroglutamine (FGln) avidity as a PET biomarker of glutamine flux and metabolism and suggest possible correlations between tumor FGln PET ... PurposeTo assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18–(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent.Materials and ...

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer’s disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.

This review article discusses PET agents, other than ¹⁸F-FDG, with the potential to monitor the response to therapy before, during, or after therapeutic intervention. This review deals primarily with non–¹⁸F-FDG PET tracers that are in the final stages of preclinical development or in the early stages of clinical application for monitoring the therapeutic response. Four sections related to the nature of the tracers are included: radiotracers of DNA synthesis, such as the 2 most promising agents, the thymidine analogs 3′-¹⁸F-fluoro-3′-deoxythymidine and ¹⁸F-1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)thymine; agents for PET imaging of hypoxia within tumors, such as ^60/62/64Cu-labeled diacetyl-bis(N⁴-methylthiosemicarbazone) and ¹⁸F-fluoromisonidazole; amino acids for PET imaging, including the most popular such agent, l-[methyl-¹¹C]methionine; and agents for the imaging of tumor expression of androgen and estrogen receptors, such as 16β-¹⁸F-fluoro-5α-dihydrotestosterone and 16α-¹⁸F-fluoro-17β-estradiol, respectively.