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Metabolic pathways for 18 F-FDG.  

Metabolic pathways for 18 F-FDG.  

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Tumors often have an increased uptake of glucose and can be detected by PET imaging using 18F-FDG. 18F-FDG is converted to 18F-FDG-6-phosphate (18F-FDG-6-P), and the usual assumption is that 18F-FDG-6-P is not a substrate for subsequent enzymatic reactions and that tumor hot spots reflect trapping of 18F-FDG-6-P. We recently found, however, that in...

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... Intestinal components were obtained using Aperio software (at least three fields per sample for each morphologic data). Immunohistochemical analysis was conducted as previously described [35,36]. Briefly, we used the standard polymer system and peroxidase methods. ...
... Because its phosphorylated form is not a substrate for the glucose-6-phosphate isomerase, most of the labeled analog accumulates in cells [35]. In turn, in normal cells 2-NBDG, similar to 18 F-FDG, is significantly metabolized to subsequent oxygenation products such as 2-18 F-fluoro-2-deoxy-6-phospho-D-gluconate ( 18 F-FD-PG1) and 2-18 F-fluoro-2-deoxy-6-phospho-D-gluconolactone ( 18 F-FD-PGL) [36], which can be released from cells and can be visible in the liver 45 min after injection [37]. Our model took advantage of 2-NBDG pharmacokinetics highlighting the active glucose uptake of the neoformed and native intestine immediately after injection and its release in the mesenteric circulation already 5 min after injection. ...
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Recent advances in the field of tissue regeneration are offering promising therapeutic options for the treatment of short bowel syndrome. This study aimed to evaluate the glucose absorptive capacity of a neoformed intestine obtained from a biological scaffold in a rodent model and the steadiness of the engrafted segment area. Twenty-four male Sprague–Dawley rats were used for this study. Under anesthesia, a patch of biological material (2.2 × 1.5 cm) was engrafted in the anti-mesenteric border of the small bowels of 12 rats. Twelve rats were sham-operated. Animals were studied at 4, 8, and 10 months postengraftment. Functional and histological analyses were performed. The functional analysis was performed using an 18F-FDG analog as a probe and the results were acquired with an optical imager. The intensity of the fluorescent signal emitted by the neointes- tine was comparable with that emitted by the native intestine in all animals and was visible after injection in the preserved mesentery. The mean intestinal volume at time of engraftment and after 10 months was 4.08 cm3 (95% CI [3.58–4.58]) and 3.26 cm3 (CI 95% [3.23–3.29]), respectively, with a mean shrinkage of 17.3% (range 10.6–23.8%), without any evidence of stenosis. Morphological analysis revealed the progression of the biological material toward a neoformed intestine similar to the native intestine, especially at 8 and 10 months. In a rodent model, we demonstrated that a neointestine, obtained from a biological scaffold showed glucose absorption and a durable increase in diameter.
... In general, reference radiometabolites were prepared via enzymatic in vitro synthesis on the basis of previously published procedures by Rokka et al. [18] and Kaarstadt et al. [15] ( Figure 1). After centrifugation (22 • C, 13,684 g), the reaction mixes were analyzed with HPLC as described for the cell samples. ...
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The glucose derivative 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[18F]FDG is said to be trapped intracellularly as 2-[18F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[18F]FDG-6-phosphate and even postulating 2-[18F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[18F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[18F]FDG metabolism with intracellular tracer accumulation, efflux and the cells’ metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[18F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[18F]FDG-6-phosphate were 2-[18F]FDMannose-6-phosphate, 2-[18F]FDG-1,6-bisphosphate and 2-[18F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells’ metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[18F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[18F]FDG metabolism might help to improve cancer research and tumor diagnosis.
... 2-Deoxy-2-fluoro-D-glucose has been used in clinical and diagnostics studies relating to animals for decades. FDG uptake and metabolism has been extensively studied in animal cells (McSheehy et al., 2000;Kaarstad et al., 2002;Southworth et al., 2003). In animal tissue, FDG is taken up by the cells via glucose transporters (Higashi et al., 1998;Brown et al., 1999;Avril, 2004;Yen et al., 2004) and phosphorylated to FDG-6-P by the action of hexokinase or glucokinase (Sols and Crane, 1954;Bessell et al., 1972;Smith, 2001). ...
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The aim of this review article is to explore and establish the current status of 2-deoxy-2-fluoro-D-glucose (FDG) applications in plant imaging. In present article, we review all the previous literature on its experimental merits to formulate a consistent and inclusive picture of FDG applications in plant imaging research. FDG is a [18F]fluorine labeled glucose analog in which C-2 hydroxyl group has been replaced by positron emitting [18F] radioisotope. FDG being a positron emitting radiotracer could allow for in vivo imaging. FDG mimics glucose chemically and structurally. Its uptake and distribution is found to be similar to that of glucose in animal models. FDG is commonly used as a radiotracer for glucose in medical diagnostics and in vivo animal imaging studies but rarely in plant imaging. Tsuji et al (2002) first reported FDG uptake and distribution in tomato plants. Later, Hattori et al (2008) described FDG translocation in intact sorghum plants and suggested that it could be used as a tracer for photoassimilate translocation in plants. These findings raised interest among other plant scientists which resulted in recent surge of research papers involving FDG as a tracer in plants. In total, there have been 7 studies describing FDG imaging applications in plants. These studies describe FDG applications ranging from monitoring radiotracer translocation to analyzing solute transport, root uptake, photoassimilates tracing, carbon allocation, or glycoside biosynthesis. Recently, Fatangare et al (2015) characterized FDG metabolism in plants which was a crucial aspect of understanding and validating FDG applications in plant research. Although all of the above studies significantly advanced our understanding of FDG translocation and metabolism in plants, it also raised new questions. Here, we take a look at the previous results cumulatively to form a comprehensive picture of FDG translocation, metabolism, and applications in plants. In conclusion, we summarize the current knowledge, discuss possible implications and limitations of previous studies, point out the open questions in the field, and comment upon the outlook of FDG applications in plants imaging.
... Synthesis and analysis of [ 18 F]FDG-6-P [ 18 F]FDG-6-P was prepared from commercially available [ 18 F]FDG (PETNET Solutions, Nottingham, UK) following a method previously described [31]. The purity of the [ 18 F]FDG-6-P product was determined by reverse-phase high-performance liquid chromatography (RP-HPLC) on an Agilent 1260 Series LC (Agilent Technologies, Sta. Clara, CA, USA) connected to Flow-RAM™ sodium iodide detector (LabLogic Systems Limited, Sheffield, UK). ...
... Synthesis and stability of [ 18 F]FDG-6-P [ 18 F]FDG-6-P was synthesised from [ 18 F]FDG as previously described [31]. The [ 18 F]FDG-6-P product was analysed by iTLC ( Figure 1a) and RP-HPLC (Figure 1b) in order to confirm yield and determine that the [ 18 (Figure 1b). ...
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Background: Management of infection is a major clinical problem. Staphylococcus aureus is a Gram-positive bacterium which colonises approximately one third of the adult human population. Staphylococcal infections can be life-threatening and are frequently complicated by multi-antibiotic resistant strains including methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([(18)F]FDG) imaging has been used to identify infection sites; however, it is unable to distinguish between sterile inflammation and bacterial load. We have modified [(18)F]FDG by phosphorylation, producing [(18)F]FDG-6-P to facilitate specific uptake and accumulation by S. aureus through hexose phosphate transporters, which are not present in mammalian cell membranes. This approach leads to the specific uptake of the radiopharmaceutical into the bacteria and not the sites of sterile inflammation. Methods: [(18)F]FDG-6-P was synthesised from [(18)F]FDG. Yield, purity and stability were confirmed by RP-HPLC and iTLC. The specificity of [(18)F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT) was confirmed with S. aureus and mammalian cell assays in vitro. Whole body biodistribution and accumulation of [(18)F]FDG-6-P at the sites of bioluminescent staphylococcal infection were established in a murine foreign body infection model. Results: In vitro validation assays demonstrated that [(18)F]FDG-6-P was stable and specifically transported into S. aureus but not mammalian cells. [(18)F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared to uninfected controls; however, the increase in signal was not significant and unexpectedly, the whole-body biodistribution of [(18)F]FDG-6-P was similar to that of [(18)F]FDG. Conclusions: Despite conclusive in vitro validation, [(18)F]FDG-6-P did not behave as predicted in vivo. However at the site of known infection, [(18)F]FDG-6-P levels were elevated compared with uninfected controls, providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose phosphates other than glucose, and therefore alternative sugars may show differential biodistribution and provide a means for specific bacterial detection.
... 2-Deoxy-2-fluoro-D-glucose (FDG) uptake and metabolism has been extensively studied in animal cells (McSheehy et al., 2000;Kaarstad et al., 2002;Southworth et al., 2003). Being the glucose analog, FDG is transported into the animal cells via the same transporters as glucose (Higashi et al., 1998;Brown et al., 1999;Avril, 2004;Yen et al., 2004). ...
... The assumption that FDG flux is only directed toward FDG-6-P, which leads to intracellular radioisotope accumulation, forms the basis of FDG application as a glucose tracer to study glucose sequestration and utilization. However, numerous studies have demonstrated that FDG metabolism in animal tissue goes beyond FDG-6-P (Kanazawa et al., 1996;McSheehy et al., 2000;Kaarstad et al., 2002;Southworth et al., 2003). These studies list 2-deoxy-2-fluoro-D-mannose (FDM), 2-deoxy-2-fluoro-D-mannose-6-phosphate (FDM-6-P), 2-deoxy-2-fluoro-D-glucose-1-phosphate (FDG-1-P), 2-deoxy-2-fluoro-D-glucose-1,6-bisphosphate, 2-deoxy -2-fluoro-D-mannose-1-phosphate (FDM-1-P), 6-phospho-2deoxy-2-fluoro-D-gluconolactone, 6-phospho-2-deoxy-2-fluoro -D-gluconate, nucleotide-diphosphate-FDG (NDP-FDG) etc. as metabolic end products of FDG in animal cells (Kanazawa et al., 1996;McSheehy et al., 2000;Bender et al., 2001;Kaarstad et al., 2002;Southworth et al., 2003). ...
... However, numerous studies have demonstrated that FDG metabolism in animal tissue goes beyond FDG-6-P (Kanazawa et al., 1996;McSheehy et al., 2000;Kaarstad et al., 2002;Southworth et al., 2003). These studies list 2-deoxy-2-fluoro-D-mannose (FDM), 2-deoxy-2-fluoro-D-mannose-6-phosphate (FDM-6-P), 2-deoxy-2-fluoro-D-glucose-1-phosphate (FDG-1-P), 2-deoxy-2-fluoro-D-glucose-1,6-bisphosphate, 2-deoxy -2-fluoro-D-mannose-1-phosphate (FDM-1-P), 6-phospho-2deoxy-2-fluoro-D-gluconolactone, 6-phospho-2-deoxy-2-fluoro -D-gluconate, nucleotide-diphosphate-FDG (NDP-FDG) etc. as metabolic end products of FDG in animal cells (Kanazawa et al., 1996;McSheehy et al., 2000;Bender et al., 2001;Kaarstad et al., 2002;Southworth et al., 2003). It is important to notice that the conversion of FDG to FDG-6-P is the first and foremost step for FDG metabolism in animal tissues and the reported F-metabolites are either situated downstream the FDG-6-P in the glycolytic pathway or arise from it. ...
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2-Deoxy-2-fluoro-d-glucose (FDG) is glucose analog routinely used in clinical and animal radiotracer studies to trace glucose uptake but it has rarely been used in plants. Previous studies analyzed FDG translocation and distribution pattern in plants and proposed that FDG could be used as a tracer for photoassimilates in plants. Elucidating FDG metabolism in plants is a crucial aspect for establishing its application as a radiotracer in plant imaging. Here, we describe the metabolic fate of FDG in the model plant species Arabidopsis thaliana. We fed FDG to leaf tissue and analyzed leaf extracts using MS and NMR. On the basis of exact mono-isotopic masses, MS/MS fragmentation, and NMR data, we identified 2-deoxy-2-fluoro-gluconic acid, FDG-6-phosphate, 2-deoxy-2-fluoro-maltose, and uridine-diphosphate-FDG as four major end products of FDG metabolism. Glycolysis and starch degradation seemed to be the important pathways for FDG metabolism. We showed that FDG metabolism in plants is considerably different than animal cells and goes beyond FDG-phosphate as previously presumed.
... It has been suggested that [ 18 F]FDG, a radioactive glucose analogue, could be used as a tracer for photoassimilates distribution in plant studies [38]. Although, [ 18 F]FDG uptake and metabolism has been extensively studied in animal cells [39][40][41], its metabolism in plant tissues is not well characterized. First, we performed thin layer chromatography (TLC) experiments to analyze whether [ 18 F]FDG is metabolized in N. attenuata plants, as has been shown in A. thaliana [21]. ...
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Although leaf herbivory-induced changes in allocation of recently assimilated carbon between the shoot and below-ground tissues have been described in several species, it is still unclear which part of the root system is affected by resource allocation changes and which signalling pathways are involved. We investigated carbon partitioning in root tissues following wounding and simulated leaf herbivory in young Nicotiana attenuata plants. Using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), which was incorporated into disaccharides in planta, we found that simulated herbivory reduced carbon partitioning specifically to the root tips in wild type plants. In jasmonate (JA) signalling-deficient COI1 plants, the wound-induced allocation of [(18)F]FDG to the roots was decreased, while more [(18)F]FDG was transported to young leaves, demonstrating an important role of the JA pathway in regulating the wound-induced carbon partitioning between shoots and roots. Our data highlight the use of [(18)F]FDG to study stress-induced carbon allocation responses in plants and indicate an important role of the JA pathway in regulating wound-induced shoot to root signalling.
... We found in our ATPase assay that FDG does not affect the ATPase activity of Pgp (Fig. 1) further supporting that it is not a substrate or inhibitor of the transporter. FDG is converted to FDG-6-P very rapidly (Kaarstad et al., 2002). FDG-6-P is not commercially available, therefore we used the 2-deoxy-glucose- 6-phosphate in our experiments, which has very close chemical characters to that of the FDG-6-P molecule and found that it does not have any influence on the ATPase activity of Pgp. ...
Article
2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp.
... These results suggest that 18 F-FDM accumulates in tumor cells through a metabolic trapping mechanism such as the one seen with 18 F-FDG. With respect to 18 F-FDG metabolism, 18 F-fluorodeoxy-6-phospho-D-gluconolactone and 18 F-fluorodeoxy-6-phospho-D-gluconate were observed in squamous carcinoma and mammary carcinoma in mice in addition to the major metabolite of 18 F-FDG-6-P at 1-3 h after injection (23). Furthermore, conversion of FDG-6-P into FDM-6-P or vice versa within sarcoma cells (24) or colon26 cells (25) has been reported. ...
Article
2-Deoxy-2-(18)F-fluoro-d-mannose ((18)F-FDM) is an (18)F-labeled mannose derivative and a stereoisomer of (18)F-FDG. Our preliminary study demonstrated that (18)F-FDM accumulated in tumors to the same extent as (18)F-FDG, with less uptake in the brain and faster clearance from the blood. However, detailed studies on the uptake of (18)F-FDM in tumors have not been conducted. We undertook this study to establish a practical method of (18)F-FDM synthesis based on an (18)F-nucleophilic substitution (SN2) reaction and to advance the biologic characterization of (18)F-FDM for potential application as a tumor-imaging agent. We synthesized 4,6-O-benzylidene-3-O-ethoxymethyl-1-O-methyl-2-O-trifluoromethanesulfonyl-β-d-glucopyranoside as a precursor for the nucleophilic synthesis of (18)F-FDM. The precursor was radiofluorinated with (18)F-KF/Kryptofix222, followed by removal of the protecting groups with an acid. (18)F-FDM was purified by preparative high-performance liquid chromatography and then subjected to in vitro evaluation regarding phosphorylation by hexokinase as well as uptake and metabolism in AH109A tumor cells. The in vivo properties of (18)F-FDM were examined in Donryu rats bearing AH109A tumor cells by biodistribution studies and imaging with a small-animal PET system. We radiosynthesized (18)F-FDM in sufficient radiochemical yields (50%-68%) with excellent purities (97.6%-98.7%). (18)F-FDM was phosphorylated rapidly by hexokinase, resulting in 98% conversion into (18)F-FDG-6-phosphate within 30 min. Tumor cells showed significant uptake of (18)F-FDM with time in vitro, and uptake was dose-dependently inhibited by d-glucose. (18)F-FDM injected into tumor-bearing rats showed greater uptake in tumors (2.17 ± 0.32 percentage injected dose per gram [%ID/g]) than in the brain (1.42 ± 0.10 %ID/g) at 60 min after injection. PET studies also revealed the tumor uptake of (18)F-FDM (quasi-standardized uptake value, 2.83 ± 0.22) to be the same as that of (18)F-FDG (2.40 ± 0.30), but the brain uptake of (18)F-FDM (1.89 ± 0.13) was ≈30% lower than that of (18)F-FDG (2.63 ± 0.26). We prepared (18)F-FDM with good radiochemical yield and purity by an SN2 reaction. We demonstrated that (18)F-FDM had adequate tumor cell uptake by a metabolic trapping mechanism and can afford high-contrast tumor images with less uptake in the brain, indicating that (18)F-FDM has almost the same potential as (18)F-FDG for PET tumor imaging, with better advantages with regard to the imaging of brain tumors.
... Possible misinterpretations of the results could be related to the fact that the rate of phosphorylation in tumors can be altered. Kaarstad and co-workers [27] demonstrated -besides 18 F-FDG-6-phosphate (P) -the formation of two secondary metabolites to 18 F-FDG-6-P ( 18 F-FD-PG1 and 18 F-FDG-1,6-P 2 ) in malignant tumor tissue after 18 F-FDG administration. However, they did not identify any of the nucleotide derivatives of 18 F-FDG-1-P or incorporation of 18 F-FDG into glycogen. ...
Article
Introduction: The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts. Methods: Subcutaneous tumors were produced in nude mice by injection of PC3 and CWR22Rv1 PCa cells. The mice were divided into two groups (Acipimox vs. controls). Acipimox (50mg/kg) was administered by oral gavage 1h before injection of tracers. 1h after i.v. co-injection of 8.2MBq (222 ± 6.0 μCi) (18)F-FDG and~0.0037 MBq (0.1 μCi) (14)C-acetate, (18)F-FDG imaging was performed using a small-animal PET scanner. Counting rates in reconstructed images were converted to activity concentrations. Quantification was obtained by region-of-interest analysis using dedicated software. The mice were euthanized, and blood samples and organs were harvested. (18)F radioactivity was measured in a calibrated γ-counter using a dynamic counting window and decay correction. (14)C radioactivity was determined by liquid scintillation counting using external standard quench corrections. Counts were converted into activity, and percentage of the injected dose per gram (%ID/g) tissue was calculated. Results: FDG biodistribution data in mice with PC3 xenografts demonstrated doubled average %ID/g tumor tissue after administration of Acipimox compared to controls (7.21 ± 1.93 vs. 3.59 ± 1.35, P=0.02). Tumor-to-organ ratios were generally higher in mice treated with Acipimox. This was supported by PET imaging data, both semi-quantitatively (mean tumor FDG uptake) and visually (tumor-to-background ratios). In mice with CWR22Rv1 xenografts there was no effect of Acipimox on FDG uptake, either in biodistribution or PET imaging. (14)C-acetate uptake was unaffected in PC3 and CWR22Rv1 xenografts. Conclusions: In mice with PC3 PCa xenografts, acute administration of Acipimox increases tumor uptake of (18)F-FDG with general improvements in tumor-to-background ratios. Data indicate that administration of Acipimox prior to (18)F-FDG PET scans has potential to improve sensitivity and specificity in patients with castration-resistant advanced PCa.
... Possible misinterpretations of the results could be related to the fact that the rate of phosphorylation in malignant cells can be altered. Kaarstad and co-workers [28] demonstrated -besides 18 F-FDG-6-phosphate (P) -the formation of two secondary metabolites to 18 F-FDG-6-P ( 18 F-FD-PG1 and 18 F-FDG-1,6-P 2 ) in malignant tumor tissue after 18 F-FDG administration. However, they did not identify any of the nucleotide derivatives of 18 F-FDG-1-P or incorporation of 18 F-FDG into glycogen. ...
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Introduction The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-D-glucose (FDG) and acetate. Methods Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco’s Modified Eagle’s Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0–1.0 mM). Then the cells were incubated with [18 F]-FDG (1 μCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for 18 F radioactivity were applied. Cell uptake studies with 14C-1-acetate under the same conditions were performed on PC3 cells. Results In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/106 cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. Conclusions Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.