Normalization of fluorine 18 fluorodeoxyglucose (FDG) uptake using blood-pool (or liver) removes the effect that tumor burden has on FDG accumulation in reference tissues, including the brain, thereby limiting variability induced by high volume disease burden. This confirms the importance of using a stable and well understood reference tissue when performing metabolic tumor response assessment and supports the addition of normalization to a reference tissue in PET Response Criteria in Solid Tumors. Purpose To examine the effect metabolic burden (tumor and/or cardiac myocyte uptake) has on fluorine 18 fluorodeoxyglucose (FDG) distribution in organs and tissues of interest. Materials and Methods Positron emission tomographic (PET)/computed tomographic (CT) scans at the Ann Arbor Veterans Affairs hospital from January to July 2015 were reviewed. A total of 107 scans (50 patients; mean age, 64.3 years ± 13.2 [standard deviation]) had metabolic tissue burden assessed by using total lesion glycolysis (TLG) obtained from autosegmentation of the tumor and/or cardiac tissue. Standardized uptake value (SUV) and subsequent normalized SUV uptake in target organs and tissues were compared with 436 FDG PET/CT scans previously reported in 229 patients as a function of TLG to describe the effect(s) that metabolic burden has on reference tissue (blood pool, liver, and brain) FDG uptake. Subsequent regression by using linear mixed-effects models was used. If the slope of the regression was significantly (P < .05) dif...

This report describes a simple technique for the preparation of [ ¹⁸ F]HF and its application to the generation of an [ ¹⁸ F]FeF species for opening sterically hindered epoxides. This easily automated one-pot procedure has been successfully employed to prepare four drug-like molecules in good yields and high molar activities, including 5-[ ¹⁸ F]fluoro-6-hydroxy-cholesterol.

Radiolabeled erythrocytes have multiple applications in nuclear medicine, including blood pool imaging. Historically they have been labeled with SPECT radionuclides. A PET blood pool imaging agent is highly desirable as it would improve clinical applications with better image quality and resolution, higher sensitivity, and dynamic scanning capabilities. With the coming of age of modern ⁶⁸Ge/⁶⁸Ga generator systems, gallium-68 is now widely accessible. In this paper we describe an updated method for the preparation of ⁶⁸Ga-labeled erythrocytes and their preliminary use in rodent blood pool imaging. A novel automated synthesis of [⁶⁸Ga]oxine using a ⁶⁸Ga/⁶⁸Ge generator and automated synthesis module is reported. [⁶⁸Ga]Oxine was synthesized in 50 ± 5% (n = 3) non-decay corrected radiochemical yield and >99% radiochemical purity. Rat and human erythrocytes were successfully labeled with the complex in 42% RCY, and the ⁶⁸Ga-labeled erythrocytes have been shown to clearly image the blood pool in a healthy rat. Human erythrocytes labelled with [⁶⁸Ga]oxine were shown to be viable up to 2 hours post-labelling, and washout of the radiolabel was minimal up to 1 hour post-labelling. Further optimization of the labeling method to translate for use in human cardiac and oncologic blood pool PET imaging studies, is underway.

Evaluating the response to immune checkpoint inhibitors (ICIs) remains an unmet challenge in triple-negative breast cancer (TNBC). The requirement for cholesterol in the activation and function of T cells led us to hypothesize that quantifying cellular accumulation of this molecule could distinguish successful from ineffective checkpoint immunotherapy. To analyze accumulation of cholesterol by T cells in the immune microenvironment of breast cancer, we leveraged the PET radiotracer, eFNP-59. eFNP-59 is an analog of cholesterol that our group validated as an imaging biomarker for cholesterol uptake in preclinical models and initial human studies. In immunocompetent mouse models of TNBC, we found that elevated uptake of exogenous labeled cholesterol analogs functions as a marker for T cell activation. When comparing ICI-responsive and -nonresponsive tumors directly, uptake of fluorescent cholesterol and eFNP-59 increased in T cells from ICI-responsive tumors. We discovered that accumulation of cholesterol by T cells increased in ICI-responding tumors that received anti–PD-1 checkpoint immunotherapy. In patients with TNBC, tumors containing cycling T cells had features of cholesterol uptake and trafficking within those populations. These results suggest that uptake of exogenous cholesterol analogs by tumor-infiltrating T cells allows detection of T cell activation and has potential to assess the success of ICI therapy.