Fully automated synthesis procedure of 4-[18F]fluorobenzaldehyde by commercial synthesizer: Amino-oxi peptide labelling prosthetic group

Automatic synthesis of 4-[18F]fluorobenzaldehyde has been developed by a commercially available TRACERlab™ FX_F−N synthesis module to be used as prosthetic group for amino-oxy functionalized peptide labelling in clinical routine application. In addition a handmade purification device (HPD) has been setup to perform automatic cartridge purification as well as to back-up the reactor where one-pot synthesis is not applicable. Cartridges for solid phase extraction such as C18, C8, phenyl has been tested to best perform purification as well as activity recovery. Radiochemical yield (RCY) at end of synthesis (EOS) was in average 67% after about 45 min (90% decay corrected at EOB). The RCY of the entire procedure was 54% with a radiochemical purity above 99%.     

4-18F-氟代丁酸及其甲酯作为PET显像剂可行性的初步研究

目的：利用PET-MF-2V-IT-I氟多功能合成模块自动化合成4-18F-氟代丁酸及其甲酯,并初步探讨其作为PET显像剂的可行性。方法前体4-溴代丁酸甲酯与18F－发生氟代反应,中间体4-18F-氟代丁酸甲酯用高压液相色谱法分离,收集保留时间在6．8～7．8 min的组分,将此组分与NaOH溶液于115℃下加热水解10 min,加入HCl调至中性,得到4-18F-氟代丁酸;稀释后过C18柱,再用20 ml注射用水清洗C18柱,0．5 ml乙醇洗脱后用生理盐水稀释,得到4-18F-氟代丁酸甲酯。分别目测两种产品的澄清度,精密试纸测定pH值、测定放射化学纯度和稳定性。正常小鼠尾静脉注射4-18F-氟代丁酸30 min后行micro PET显像。结果4-18F-氟代丁酸和4-18F-氟代丁酸甲酯的自动合成时间分别为40 min和20 min,放化收率分别为35%和50%（均未经时间校正）, pH值分别为6．5和7．1,产品放射化学纯度均>95%。二者均澄清无颗粒,室温放置30 min后均出现脱氟现象。正常小鼠micro PET显像结果显示,脊柱有明显的放射性浓聚,表明4-18F-氟代丁酸在体内脱氟,肠道亦有较高的放射性摄取。结论4-18F-氟代丁酸及其甲酯的合成方法操作简便,合成时间短,且放化收率也较高,但因其不稳定,不适合用作PET显像剂进行进一步研究。但小鼠micro PET显像结果提示,18F-氟代丁酸类似物在肠道疾病诊断中有潜在研究价值。     

Tritium in [O]water containing [F]fluoride for [F]FDG synthesis

The presence of tritium in enriched [¹⁸O]water irradiated with 9.6 MeV protons used to produce [¹⁸F]fluoride by the ¹⁸O(p, n)¹⁸F reaction was inferred from the cross sections and threshold energies of the ¹⁸O(p, t)¹⁶O reaction, and the existence of tritium was confirmed experimentally. Tritium was also detected in both [¹⁸O]water recovered for recycling and waste acetonitrile solutions. The purified [¹⁸F]FDG was not contaminated with ³H. The amount of ³H discharged into the air was far less than the International Basic Safety Standard Level.     

Comparison of two full automatic synthesis methods of 9-(4-[F]fluoro-3-hydroxymethylbutyl)guanine using different chemistry modules

We have developed synthesis methods for 9-(4-[¹⁸F]fluoro-3-hydroxymethylbutyl)guanine ([¹⁸F]FHBG) using two commercial automatic chemistry modules, Tracerlab MX and Explora RN, and compared radiochemical yields. Synthesis conditions and sequence programs were modified for two modules because both these modules have different mechanical structures, including heater type, vacuum system, reactor, and tubing size. Synthesis using the Tracerlab MX module showed a 21.0±3.8% yield of radiochemical, which was 98±0.9% pure; the total preparation time was 63.0±5.0 min including an HPLC purification step. In contrast, synthesis using the Explora RN module showed a 32.0±1.2% yield of radiochemical, which was 99.0±0.6% pure; the total preparation time was 38±2 min, using different HPLC purification conditions and without the HPLC solvent evaporation step.     

Fully automated one-pot synthesis of [18F]fluoromisonidazole

A (18)F-labeled fluoromisonidazole (1H-1-(3-[(18)F]fluoro-2-hydroxypropyl)-2-nitroimidazole, [(18)F]FMISO) was prepared via a one-pot, two-step synthesis procedure using a modified commercial Tracerlab FX(F-N) synthesis module. Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol using no-carrier-added [(18)F]fluoride, followed by hydrolysis of the protecting group with 1 mol/L HCl and purification with Sep-Paks instead of HPLC, gave [(18)F]FMISO. The overall radiochemical yield with no decay correction was greater than 40%, the whole synthesis time was less than 40 min and the radiochemical purity was greater than 95%. The new automated synthesis procedure can be applied to the fully automated synthesis of [(18)F]FMISO using a commercial FDG synthesis module.     

Rapid synthesis of [F]FDG without an evaporation step using an ionic liquid

In this study, we describe a new 2-[¹⁸F]fluoro-2-deoxy- -glucose ([¹⁸F]FDG) synthesis without a distillation step. This involves fluorinating in an ionic liquid-containing medium. A test for the effective elution of [¹⁸F]fluoride from the anion exchange resin showed the proper selection of the base and the required eluant composition, which is an essential requirement for the automation of [¹⁸F]FDG synthesis. An ¹⁸F-labeling study by nucleophilic substitution showed that the major factors controlling the yield were the temperature and the reaction medium composition. The ¹⁸F-fluorination proceeded with a labeling efficiency of 74.6±7.4% (n=8) for optimized conditions. Alkaline hydrolysis and purification carried out in the liquid phase provided a final decay-corrected [¹⁸F]FDG yield of 59.1±5.1% (n=3), a radiochemical purity of 91.9±3.7% (n=3), and a reaction time of 13 min. Alkaline hydrolysis and purification carried out in the solid phase provided a final decay-corrected [¹⁸F]FDG yield of 48.8±6.0% (n=3), a radiochemical purity of 96.0±4% (n=3), and a reaction time of 19 min. The rapid and straightforward synthesis of [¹⁸F]FDG can be achieved by eliminating all evaporation steps, which is made possible by the use of ionic liquid-containing media for the fluorination step.     

Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver

We have previously shown that the accumulation of fluorine-18-labeled fluoromisonidazole ([¹⁸F]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We determined the activity from administered [¹⁸F]FMISO in relation to the hepatic oxygen availability and the partial pressure of oxygen in tissue (tPO₂) to define a critical oxygen delivery on a regional basis. [¹⁸F]FMISO was injected 2 h after onset of regional liver hypoxia due to arterial occlusion of branches of the hepatic artery in 10 domestic pigs. During the experimental procedure the fractional concentration of inspired oxygen (FiO₂) was set to 0.67 in group A ( N=5) and to 0.21 in group B ( N=5) animals. Immediately before sacrifice, the tPO₂ was determined in normal flow and flow-impaired liver segments. The standardized uptake values (SUV) for [¹⁸F]FMISO was calculated from 659 single tissue samples obtained 3 h after injection of approximately 10 MBq/kg body weight [¹⁸F]FMISO and was compared with the regional total hepatic oxygen delivery (DO₂) calculated from the regional arterial and portal venous flow (based on ¹⁴¹Ce- and ^99mTc-microspheres measurements) and the oxygen content of the arterial and portal venous blood. In 121 tPO₂-measured liver tissue samples, the mean DO₂ was significantly decreased in occluded liver tissue samples [group A: 0.063 (0.044–0.089); group B: 0.046 (0.032–0.066)] compared to normal flow segments [group A: 0.177 (0.124–0.252); group B: 0.179 (0.128–0.25) mL·min⁻¹·g⁻¹; geometric mean (95% confidence limits); p < 0.01 in group A and p < 0.001 in group B]. The tPO₂ of occluded segments [group A: 5.1 (3.2–8.1); group B: 3.9 (2.4–6.2) mm Hg] was significantly decreased compared to normal flow segments [group A: 20.2 (12.6–32.5); group B: 22.4 (14.3–35.2) mm Hg; p < 0.01 in group A and p < 0.001 in group B]. Three hours after [¹⁸F]FMISO administration, the mean [¹⁸F]FMISO SUV determined in tPO₂-measured occluded segments was significantly higher [group A: 4.08 (3.12–5.34), group B: 5.43 (4.14–7.13)] compared to normal liver tissue [group A: 1.57 (1.2–2.06), group B: 1.5 (1.16–1.93); p < 0.001 for both groups]. The [¹⁸F]FMISO SUV allowed prediction of the tPO₂ with satisfying accuracy in hypoxic regions using the exponential regression curve { [¹⁸F]FMISO=1.05+6.7^{(−0.117 tPO₂}); r²=0.75;p < 0.001}. In addition, regardless of ventilation conditions, a significant exponential relationship between the DO₂ and the [¹⁸F]FMISO SUV was found ( r²=0.39,p < 0.001). Our results suggest that the reduction of the oxygen delivery below the critical range of 0.1–0.11 mL·min⁻¹·g⁻¹ regularly causes liver tissue hypoxia. The severity of hypoxia is reflected by the [¹⁸F]FMISO accumulation and allows the in vivo estimation of the tPO₂ in hypoxic regions.     

Improved synthesis of anti-[F]FACBC: improved preparation of labeling precursor and automated radiosynthesis

The non-natural amino acid anti-1-amino-3-[¹⁸F]fluorocyclobutyl-1-carboxylic acid (FACBC) has shown promise for tumor imaging with positron emission tomography. An improved synthesis of the precursor of anti-[¹⁸F]FACBC has been devised which demonstrates high stereoselectivity and suitability for large-scale preparations. An automated radiosynthesis has been developed which provides anti-[¹⁸F]FACBC in 24% decay-corrected yield. Additionally, the major non-radioactive species present in doses of anti-[¹⁸F]FACBC has been identified as anti-1-amino-3-hydroxycyclobutane-1-carboxylic acid. Together, these results are important steps towards the routine production of anti-[¹⁸F]FACBC for human use.     

NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

Purpose The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO).Methods [¹⁸F]FMISO PET imaging was performed with the dedicated small-animal PET scanner NanoPET (Oxford Positron Systems) and ten different human tumour xenografts in nude mice as well as B16 melanoma tumours in syngeneic Balb/c mice. For comparison, [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) PET scans were also performed in the mice bearing human tumour xenografts.Results In 10 out of 11 experimental tumour models, [¹⁸F]FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter- and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR_75% and TMRR₅ (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [¹⁸F]FMISO uptake in the tumours. The variability observed in [¹⁸F]FMISO uptake was related neither to tumour size nor to the injected mass of the radiotracer. The pattern of normoxic and hypoxic regions within the human tumour xenografts, however, correlated with glucose metabolism as revealed by comparison of [¹⁸F]FDG and [¹⁸F]FMISO images.Conclusion This study demonstrates the feasibility and utility of [¹⁸F]FMISO for imaging murine tumour models using NanoPET.     

Automated synthesis of n.c.a. [F]FDOPA via nucleophilic aromatic substitution with [F]fluoride

An improved, automated synthesis of [¹⁸F]FDOPA including four synthetic steps (fluorination, reductive iodination, alkylation and hydrolysis) is reported with each step optimized individually. In a home-made automatic synthesizer, 9064±3076 MBq of [¹⁸F]FDOPA were produced within 120 min from EOB (n=5). Radiochemical purity and enantiomeric excess were both 95%. Specific activity was ca. 50 GBq/μmol at EOS. This automatically operable synthesis is well suited for the multi-patient-dose routine production of n.c.a. [¹⁸F]FDOPA.     

PET/CT in patients with hepatocellular carcinoma using [18F]fluorocholine: preliminary comparison with [18F]FDG PET/CT

Purpose The diagnostic accuracy of [¹⁸F]fluorodeoxyglucose (FDG) PET is insufficient to characterise hepatocellular carcinoma (HCC) in liver masses and to diagnose all cases of recurrent HCC. HCC has been reported to take up [¹¹C]acetate, but routine use of this tracer is difficult. Choline is another tracer of lipid metabolism, present in large amounts in HCC. In a proof-of-concept study, we evaluated [¹⁸F]fluorocholine (FCH) uptake by HCC and compared FCH PET/CT with FDG PET/CT.Methods Twelve patients with newly diagnosed (n=8) or recurrent HCC (n=4) were prospectively enrolled. HCC was assessed by histology in eight cases and by American Association for the Study of Liver Diseases (AASLD) criteria in four cases. All patients underwent whole-body PET/CT 10 min after injection of 4 MBq/kg FCH. Within 1 week, 9 of the 12 patients also underwent whole-body FDG PET/CT 1 h after injection of 5 MBq/kg FDG.Results The per-patient analysis showed a detection rate of 12/12 using FCH PET/CT for both newly diagnosed and recurrent HCC. The median signal to noise ratio was 1.5±0.38. There was a trend towards a higher FCH SUV_max in well-differentiated HCC (15.6±7.9 vs 11.9±0.9, NS). Of the nine patients who underwent FCH and FDG PET/CT, all nine were positive with FCH whereas only five were positive with FDG.Conclusion FCH provides a high detection rate for HCC, making it potentially useful in the initial evaluation of HCC or in the detection of recurrent disease. The favourable result of this proof-of-concept study opens the way to a phase III prospective study.     

Automated radiosynthesis of N-succinimidyl 3-(di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SiFB) for peptides and proteins radiolabeling for positron emission tomography

Recently, silicon fluoride building blocks (SiFA) have emerged as valuable and promising tools to overcome challenges in the labeling of peptides and proteins for positron emission tomography (PET). Herein, we report a fully automated synthesis of N-succinimidyl 3-(di-tert-butyl[¹⁸F]fluorosilyl)benzoate ([¹⁸F]SiFB) by a commercially available Scintomics Hot Box 3 synthesis module, to be used as a prosthetic group for peptide and protein labeling. The drying of K2.2.2./K ¹⁸F complex was performed according to the Munich method modified by our group (avoiding azeotropic drying) using oxalic acid to neutralize the base from the ¹⁸F⁻ containing QMA eluent. This K2.2.2./K ¹⁸F complex was then used for SiFA ¹⁸F–¹⁹F isotopic exchange followed by a fast purification by a solid-phase-extraction (SPE) to afford [¹⁸F]SiFB with an average preparative radiochemical yield (RCY) of 24±1% (non-decay corrected (NDC)) within a synthesis time of 30 min. The [¹⁸F]SiFB produced by automated synthesis was then used for the ¹⁸F-labeling of rat serum albumin (RSA) as a proof of applicability.     

Fully automated synthesis of O-(3-[F]fluoropropyl)-L-tyrosine by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin

A fully automated synthesis of O-(3-[¹⁸F]fluoropropyl)-L-tyrosine (FPT), an amino acid tracer for tumor imaging with positron emission tomography, is described. FPT was prepared by a two-step reaction sequence. Direct nucleophilic fluorination substitution of [¹⁸F]fluoride with 1,3-di(4-methylphenylsulfonyloxy)propane on a quaternary 4-(4-methylpiperidinyl)pyridinium functionalized polystyrene anion exchange resin, followed by [¹⁸F]fluoro-1-(4-methylphenylsulfonyloxy)propane yielded FPT. The overall radiochemical yield with no decay correction was about 12%; the whole synthesis time was about 52 min, and the radiochemical purity was above 95%.     

Improved quality control of [18F]FDG by HPLC with UV detection

A conventional high-performance liquid chromatographic (HPLC) method for the analysis of 2-fluoro-2-deoxy-d-glucose (FDG) and 2-deoxy-2-chloro-d-glucose (ClDG) in [¹⁸F]FDG preparations is described. This method was based on a postcolumn derivatization with 2-cyanoacetamide (2-CA) and UV detection. FDG and ClDG were separated on a normal-phase column using acetonitrile/water as the mobile phase. The eluate was mixed with 2-CA in sodium borate buffer solution at the outlet of a PTFE coil (10 m×0.5 mm id) from the column, and the reaction was carried out at 100°C during the passage through the coil. The UV absorbance of the resultant product was monitored at 276 nm. Under optimum conditions, the detection limits [signal-to-noise (S/N) ratio=3] for FDG and ClDG were 0.31 and 0.17 μg/ml for a 20-μl injection volume, respectively, and the linearity ranges were 0.5–100 μg/ml for both compounds. The intra- and interday reproducibilities were better than 2.2% [relative standard deviation (R.S.D.)]. This HPLC separation procedure is also useful for determining the radiochemical purity of [¹⁸F]FDG preparations since it allows the analysis of 2-[¹⁸F]fluoro-1,3,4,6-tetra-O-acetyl-d-glucose ([¹⁸F]TAG), partially hydrolyzed [¹⁸F]TAG and [¹⁸F]F⁻. This method can be used at many positron emission tomography (PET) facilities since it does not require an expensive, sophisticated electrochemical detector.     

Synthesis of [18F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers

Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2′,3′-di-O-acetyl-5′-deoxy-5-nitro-N⁴-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5′-deoxy-5-fluoro-N⁴-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5′-deoxy-5-[¹⁸F]fluoro-N⁴-(pentyloxycarbonyl)cytidine ([¹⁸F]Xeloda; [¹⁸F]1) was prepared by nucleophilic substitution of the nitro-precursor with K¹⁸F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20–30% radiochemical yields.     

Radiolabeling and in vitro and in vivo evaluation of [18F]-FE-DABP688 as a PET radioligand for the metabotropic glutamate receptor subtype 5

INTRODUCTION: Fluoroethyl-desmethyl-ABP688 (FE-DABP688) is a novel derivative of the previously described positron emission tomography (PET) ligand 3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-[11C]-methyl-oxime. FE-DABP688 was radiolabeled with fluorine-18 and characterized as a PET imaging agent for the metabotropic glutamate receptor subtype 5 (mGluR5). METHODS: FE-DABP688 was radiolabeled by reacting 2-[18F]-fluoroethyl tosylate with the sodium salt of 3-(pyridin-2-ylethynyl)-cyclohex-2-enone-oxime in dry DMF. The in vitro affinity of [18F]-FE-DABP688 for mGluR5 was determined by Scatchard analysis of saturation binding data using rat whole-brain membranes (without cerebellum). Further in vitro characterization of the tracer involved plasma stability and lipophilicity testing. In vivo evaluation of [18F]-FE-DABP688 was performed by postmortem biodistribution experiments and PET studies in rats using the dedicated small-animal PET tomograph quad-HIDAC. RESULTS: The radiotracer was obtained in good radiochemical yields in an overall synthesis time of 150 min. The radiochemical yield after semipreparative HPLC was 25+/-8% (n>7, decay corrected), and specific activity was 30+/-5 GBq/micromol (n>7). [18F]-FE-DABP688 exhibited optimal lipophilicity with a logD value of 2.1+/-0.1 and high plasma stability. Saturation assays of [(18)F]-FE-DABP688 revealed a single high-affinity binding site with a dissociation constant (Kd) of 1.6+/-0.4 nM and a Bmax value of 119+/-24 fmol/mg protein. PET scanning indicated radioactivity uptake in mGluR5-rich regions such as the hippocampus, striatum and cortex, while radioactivity accumulation in the cerebellum, a region with negligible mGluR5 density, was significantly lower. Biodistribution studies showed a similar distribution pattern of [18F]-FE-DABP688 binding in the brain. The hippocampus-to-cerebellum and striatum-to-cerebellum ratios were 1.81+/-0.16 and 1.93+/-0.36, respectively. Blocking studies using coinjection of [18F]-FE-DABP688 and unlabeled 2-methyl-6-((3-methoxyphenyl)ethynyl)-pyridine (1 mg/kg) revealed more than 45% specific binding in the hippocampus and striatum, thus demonstrating the in vivo specificity of tracer binding. CONCLUSIONS: [18F]-FE-DABP688 may be a useful PET tracer for imaging mGluR5 in rodents.     

Tumor viability evaluation by positron emission tomography with [18F]FDG in the liver metastasis rat model

We prepared a liver metastatic tumor model by injection of rat colon adenocarcinoma cells to Fischer F344 rats through portal vein, and applied positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) ([18F]FDG-PET) to this model. At an early stage of the model, multiple small tumor nodules appeared in the inferior lobes of the livers, and extended later into the superior lobes. To evaluate the tumor growth and tumor viability at the early stage, we proposed a new concept, tumor viability index (TVI), instead of the standardized uptake value (SUV) of the [18F]FDG uptake. The TVI was defined by subtracting the signal based on the normal liver from the total signal in the whole liver including tumor nodules: (whole liver SUV-normal liver SUV) x ml of whole liver region of interest (ROI). For the signal of the whole liver, ROIs were placed on six slices covering the whole liver, and the ROI of normal liver region was located in the superior lobe of the liver. The average TVI values increased with tumor growth and significantly correlated with the numbers of tumor nodules. The new concept may be useful for evaluating the tumor viability non-invasively and quantitatively by [18F]FDG-PET.     

Automated synthesis and purification of [F]bromofluoromethane at high specific radioactivity

[¹⁸F]Bromofluoromethane was synthesised from dibromomethane by substitution of bromine with [¹⁸F]fluoride. The synthesis and separation of the [¹⁸F]bromofluoromethane were automated. [¹⁸F]Bromofluoromethane was used to convert a phenolic and a thiophenolic precursor into a labelled ether and thioether, respectively. The specific radioactivity of these labelled products was determined with both high-performance liquid chromatography (with UV-absorbance detection) and liquid chromatography (with mass spectrometric detection). The median for the specific radioactivity, corrected at the end of radionuclide production, was 934 GBq/μmol (range 40–9900 GBq/μmol; n=83).     

[<Superscript>18</Superscript>F]EF3 is not superior to [<Superscript>18</Superscript>F]FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model

Purpose  The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[¹⁸F],3,3-trifluoropropyl)acetamide ([¹⁸F]EF3) with the reference hypoxia tracer [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO). Methods  [¹⁸F]EF3 or [¹⁸F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial distribution of radioactivity was defined by autoradiography on frozen tumour sections. Results  The blood clearance of [¹⁸F]EF3 was faster than that of [¹⁸F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing T/B ratios as a function of time post tracer injection (p.i.). The maximal [¹⁸F]EF3 tumour uptake, compared to the maximum [¹⁸F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution. Conclusions  [¹⁸F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [¹⁸F]FMISO at 2 h p.i. Although [¹⁸F]EF3 is a promising non-invasive tracer, it is not superior over [¹⁸F]FMISO for the visualisation of tumour hypoxia. No significant differences between [¹⁸F]EF3 and [¹⁸F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention.     

Comparison of pharmacokinetic MRI and [18F] fluorodeoxyglucose PET in the diagnosis of breast cancer: initial experience

It was the aim of this methodology-oriented clinical pilot study to compare the potential of dynamic MRI and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) for the detection and characterization of breast cancer. Fourteen women with suspicious breast lesions were examined. The MRI data were acquired with a turbo fast low-angle shot sequence and analyzed using a pharmacokinetic model. Emission data were detected in the sensitive 3D modus, iteratively reconstructed, and superimposed onto corresponding transmission images. In the 14 patients, 13 breast masses with a suspicious contrast enhancement and FDG uptake were detected. For these lesions, no statistically significant correlation between evaluated MR and PET parameters was found. Of the 9 histologically confirmed carcinomas, 8 were correctly characterized with MRI and PET. Two inflammatory lesions were concordantly classified as cancer. Moreover, dynamic MRI yielded another false-positive finding. In 6 patients, PET detected occult lymph node and/or distant metastases. Although both functional imaging techniques provide independent tissue information, the results concerning the diagnosis of primary breast lesions were almost identical. An advantage of PET, however, is its ability to localize lymph node involvement and distant metastases as an integral part of the examination.