Antibody fragments labeled with fluorine-18 and gallium-68: In vivo comparison with indium-111 and iodine-125-labeled fragments

Although monoclonal antibodies have been radiolabeled with many different radionuclides, the application of positron emission tomography (PET) to the imaging of radiolabeled antibodies has been limited to the investigation of a small number of long-lived radionuclides. In this study, we labeled F(ab′)₂ fragments of a mouse monoclonal antibody (BB5-G1) specific for a human parathyroid surface antigen with the positron emitting radionuclides, gallium-68 and fluorine-18. The biodistribution of the fragments was evaluated in a nude mice model and the results were compared to those obtained with fragments labeled with iodine-125 and indium-111 using conventional labeling techniques. All labeled fragments bound to human parathyroid tissue implanted in nude mice, with parathyroid-to-muscle ratios reaching as high as 10:1, 4 h after administration. A major difference was observed in the uptake and clearance of the various labeled fragments through the kidney. The halogen activity cleared, but the metal radioactivity was retained in the kidney. The results indicate that the fluorine-18 or gallium-68 labeled fragment may be useful for parathyroid imaging with positron emission tomography.     

Site-selective radiolabeling of peptides by 18F-fluorobenzoylation with [18F]SFB in solution and on solid phase: a comparative study

Peptides labeled with short-lived positron-emitting radionuclides are of outstanding interest as probes for molecular imaging by positron emission tomography (PET). Herein, the site-selective incorporation of fluorine-18 into lysine-containing peptides using the prosthetic labeling agent N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) is described. The reaction of [¹⁸F]SFB with four biologically relevant resin-bound peptides was studied and optimized. For comparison, each peptide was ¹⁸F-fluorobenzoylated in solution under different conditions and the product distribution was analyzed confirming the advantages of the solid-phase approach. The method’s feasibility for selective radiolabeling either at the N-terminus or at the lysine side chain was demonstrated. Labeling on solid phase with [¹⁸F]SFB resulted in crude ¹⁸F-fluorobenzoylpeptides whose radiochemical purities were typically greater than 90% and that could be prepared in synthesis times from 65 to 76?min.     

18F-fluorothiols: a new approach to label peptides chemoselectively as potential tracers for positron emission tomography

[(18)F]Fluorothiols are a new generation of peptide labeling reagents. This article describes the preparation of suitable methanesulfonyl precursors and their use in no-carrier-added radiosyntheses of (18)F-fluorothiols. The preparations of (3-[(18)F]fluoropropylsulfanyl)triphenylmethane, (2-[2-[2-(2-[(18)F]fluoroethoxy)ethoxy]ethoxy]ethylsulfanyl)triphenylmethane, and 4-[(18)F]fluoromethyl-N-[2-triphenylmethanesulfanyl)ethyl]benzamide starting from the corresponding methanesulfonyl precursors were investigated. Following the removal of the triphenylmethane protecting group, the (18)F-fluorothiols were reacted with the N-terminal chloroacetylated model peptide ClCH(2)C(O)-LysGlyPheGlyLys. The corresponding radiochemical yields of (18)F-labeled isolated model peptide, decay-corrected to (18)F fluoride, were 10%, 32%, and 1%, respectively. These results indicate a considerable potential of (18)F-fluorothiols for the chemoselective labeling of peptides as tracers for positron emission tomography (PET).     

N-Succinimidyl 4-[(18)F]-fluoromethylbenzoate-labeled dimeric RGD peptide for imaging tumor integrin expression

RGD peptides, radiolabeled with (18)F, have been used in the clinic for PET imaging of tumor angiogenesis in cancer patients. RGD peptides are typically labeled using a prosthetic group such as N-succinimidyl 4-[(18)F]-fluorobenzoate ([(18)F]SFB) or 4-nitrophenyl 2-[(18)F]-fluoropropionate ([(18)F]NPFP). However, the complex radiosynthetic procedures have impeded their broad application in clinical studies. We previously radiolabeled proteins and peptides with the prosthetic group, N-succinimidyl 4-[(18)F]-fluoromethylbenzoate ([(18)F]SFMB), which was prepared in a simple one-step procedure. In this study, we labeled a PEGylated cyclic RGD peptide dimer, PEG(3)-E[c(RGDyK)](2) (PRGD2), using [(18)F]SFMB and evaluated for imaging tumor αvβ3 integrin expression with positron emission tomography (PET). [(18)F]SFMB was prepared in one step using [(18)F]fluoride displacement of a nitrobenzenesulfonate leaving group under mild reaction conditions followed by HPLC purification. The (18)F-labeled peptide, [(18)F]FMBPRGD2 was prepared by coupling PRGD2 with [(18)F]SFMB in pH 8.6 borate buffer and purified with HPLC. The direct labeling on BMBPRGD2 was also attempted. A Siemens Inveon PET was used to image the uptake of the [(18)F]FMBPRGD2 into a U87MG xenograft mouse model. [(18)F]FMBPRGD2, was prepared with a 15% overall radiochemical yield (uncorrected) in a total synthesis time of 90?min, which was considerably shorter than the preparation of [(18)F]SFB- and [(18)F]NPFP-labeled RGD peptides. The direct labeling, however, was not successful. High quality microPET images using [(18)F]FMBPRGD2 clearly visualized tumors by 15?min with good target to background ratio. Early tracer accumulation in the bladder suggests fast renal clearance. No obvious bone uptake can be detected even at 4-h time point indicating that fluorine attachment is stable in mice. In conclusion, N-succinimidyl 4-[(18)F]-fluoromethylbenzoate ([(18)F]SFMB) prosthetic group can be a good alternative for labeling RGD peptides to image αvβ3 integrin expression and for labeling other peptides.     

Synthesis of p-(di-tert-butyl[(18)F]fluorosilyl)benzaldehyde ([(18)F]SiFA-A) with high specific activity by isotopic exchange: a convenient labeling synthon for the (18)F-labeling of N-amino-oxy derivatized peptides

The syntheses of different (18)F-labeled peptides using the highly effective labeling synthon p-(di- tert-butylfluorosilyl) benzaldehyde ([ (18)F]SiFA-A) for the development of (18)F-radiopharmaceuticals for oncological positron emission tomography (PET) is reported. The novel and mild labeling technique for the radiosynthesis of [ (18)F]SiFA-A, based on an unexpectedly efficient isotopic (19)F- (18)F exchange, yielded the (18)F-synthon [ (18)F]SiFA-A in almost quantitative yields in high specific activities between 225 and 680 GBq/micromol (6081-18 378 Ci/mmol) without applying HPLC purification. The [ (18)F]SiFA-A was finally used to label the N-terminal amino-oxy (N-AO) derivatized peptides AO-Tyr (3)-octreotate (AO-TATE), cyclo(fK(AO-N)RGD and N-AO-PEG 2-[D-Tyr-Gln-Trp-Ala-Val-betaAla-His-Thi-Nle-NH 2] (AO-BZH3, a bombesin derivative) in high radiochemical yields. Density functional theory (DFT) calculations confirmed high efficiency of the isotopic exchange, which is predicted to proceed via a pentacoordinate siliconate intermediate dissociating immediately to form the radiolabeled [ (18)F]SiFA-A.     

Solid-phase synthesis of 2-[18F]fluoropropionyl peptides

The 2-[(18)F]fluoropropionic (2-[(18)F]FPA) acid is used as a prosthetic group for radiolabeling proteins and peptides for targeted imaging using positron emission tomography (PET). Radiolabeling of compounds with more than one acylable functional group can lead to complex mixtures of products; however, peptides can be labeled regioselectively on the solid phase. We investigated the use of a solid-phase approach for the preparation of 2-[(18)F]fluoropropionyl peptides. [(18)F]FPA was prepared and conjugated to the peptides attached to the solid phase support. The (18)F-labeled peptides were obtained in 175 min with decay corrected yields of 10% (related to [(18)F]fluoride) and with a purity of 76-99% prior HPLC purification. The suitability of various coupling reagents and solid supports were tested for radiolabeling of several peptides of various lengths.     

F-18 Labeling Protocol of Peptides Based on Chemically Orthogonal Strain-Promoted Cycloaddition under Physiologically Friendly Reaction Conditions

We introduce the high-throughput synthesis of various (18)F-labeled peptide tracers by a straightforward (18)F-labeling protocol based on a chemo-orthogonal strain-promoted alkyne azide cycloaddition (SPAAC) using aza-dibenzocyclootyne-substituted peptides as precursors with (18)F-azide synthon to develop peptide based positron emission tomography (PET) molecular imaging probes. The SPAAC reaction and subsequent chemo-orthogonal purification reaction with azide resin proceeded quickly and selectively under physiologically friendly reaction conditions (i.e., toxic chemical reagents-free, aqueous medium, room temperature, and pH ≈7), and provided four (18)F-labeled tumor targetable bioactive peptides such as cyclic Arg-Gly-Asp (cRGD) peptide, bombesin (BBN), c-Met binding peptide (cMBP), and apoptosis targeting peptide (ApoPep) in high radiochemical yields as direct injectable solutions without any HPLC purification and/or formulation processes. In vitro binding assay and in vivo PET molecular imaging study using the (18)F-labeled cRGD peptide also demonstrated a successful application of our (18)F-labeling protocol.     

Bilan initial d’imagerie de l’adénocarcinome pancréatique : données de la littérature sur la place actuelle de la tomographie par émission de positons au 18F-fluorodéoxyglucose (TEP FDG)

In pancreatic adenocarcinoma, initial imaging is essential to better select patients for surgery. Recent literature analysis of F18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) in pancreatic adenocarcinoma is summarized in the present article. Performances of FDG PET in the fields of lymph node involvement, metastatic involvement and therapeutic efficacy assessment are described for its correct use in pancreatic adenocarcinoma.     

18F]FDG labeling of neural stem cells for in vivo cell tracking with positron emission tomography: inhibition of tracer release by phloretin

The introduction of neural stem cells into the brain has promising therapeutic potential for the treatment of neurodegenerative diseases. To monitor the cellular replacement therapy, that is, to determine stem cell migration, survival, and differentiation, in vivo tracking methods are needed. Ideally, these tracking methods are noninvasive. Noninvasive tracking methods that have been successfully used for the visualization of blood-derived progenitor cells include magnetic resonance imaging and radionuclide imaging using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The SPECT tracer In-111-oxine is suitable for stem cell labeling, but for studies in small animals, the higher sensitivity and facile quantification that can be obtained with PET are preferred. Here the potential of 2'-[18F]fluoro-2'-deoxy-D-glucose ([18F]-FDG), a PET tracer, for tracking of neural stem cell (NSCs) trafficking toward an inflammation site was investigated. [18F]-FDG turns out to be a poor radiopharmaceutical to label NSCs owing to the low labeling efficiency and substantial release of radioactivity from these cells. Efflux of [18F]-FDG from NSCs can be effectively reduced by phloretin in vitro, but inhibition of tracer release is insufficient in vivo for accurate monitoring of stem cell trafficking.     

Quantitative assessment of lipoprotein metabolism by positron emission tomography with an 18F-containing residualizing label

Residualizing labels for proteins are designed to remain entrapped within cells following uptake and degradation of the carrier protein. In the present work we report the synthesis of a novel residualizing label, N-lactitol-S-([¹⁸F]fluorophenacyl)-cysteamine ([¹⁸F]LCSH, and its use for quantifying the accumulation of low density lipoprotein in tissues in vivo by positron emission tomography (PET). The retention of degradation products in tissues from lipoprotein or from other rapidly catabolized protein pharmaceuticals tagged with [¹⁸F]LCSH reduces leakage of tracer into the plasma compartment. Thus, residualizing labels provide a valuable tool for enhancing signal-to-noise ratios, even during the relatively short interval of PET studies.     

Fluoro-pegylated (FPEG) imaging agents targeting Abeta aggregates

A novel approach of producing positron emission tomography (PET) imaging agents through the formation of bioconjugates based on a pegylation-fluorination strategy resulting in fluoro-pegylated (FPEG) molecules is reported. This approach offers a simple and easy method by which to incorporate 18F in the target molecule without an appreciable increase in the lipophilicity. After 18F labeling, this convenient approach leads to PET imaging probes binding to Abeta aggregates in the brain (an important factor associated with Alzheimer's disease) using the known core structures, such as [2-(4-dimethylaminophenyl)-vinyl]-benzoxazol (3') or 2-phenylbenzothiazole (4). This approach appears to be effective in some core structures, but it cannot be uniformly applied to all structures.     

A novel prosthetic group for site-selective labeling of peptides for positron emission tomography

Efficient methodologies for the radiolabeling of peptides with [(18)F]fluoride are a prerequisite to enabling commercialization of peptide-containing radiotracers for positron emission tomography (PET) imaging. It was the purpose of this study to investigate a novel chemoselective ligation reaction comprising conjugation of an [(18)F]-N-methylaminooxy-containing prosthetic group to a functionalized peptide. Twelve derivatives of general formula R1-CO-NH-Lys-Gly-Phe-Gly-Lys-OH were synthesized where R1 was selected from a short list of moieties anticipated to be reactive toward the N-methylaminooxy group. Conjugation reactions were initially carried out with nonradioactive precursors to assess, in a qualitative manner, their general suitability for PET chemistry with only the most promising pairings progressing to full radiochemical assessment. Best results were obtained for the ligation of O-[2-(2-[(18)F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine 18 to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor 10 in acetate buffer (pH 5) after 1 h at 70 degrees C. The non-decay-corrected isolated yield was calculated to be 8.5%. The most encouraging result was observed with the combination 18 and 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, 9, where the conjugation reaction proceeded rapidly to completion at 30 degrees C after only 5 min. The corresponding non-decay-corrected radiochemical yield for the isolated (18)F-labeled product 27 was 12%. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides.     

18F]fluoroacetate positron emission tomography for hepatocellular carcinoma and metastases: an alternative tracer for [11C]acetate?

[11C]Acetate (ACT) positron emission tomography/computed tomography (PET/CT) is useful in the detection of hepatocellular carcinoma (HCC). This study aimed to evaluate whether [18F]fluoroacetate (FAC) could be an alternative analogue of [11C]ACT for the diagnosis of HCC. [18F]FAC was synthesized using the precursor t-butyl 2-(methanesulfonyloxy)ethanoate. Five volunteer patients with known HCC were recruited after consent. Whole-body [18F]FAC PET/CT was performed at 20 minutes and 1 hour postinjection and compared to [11C]ACT PET/CT at 20 minutes postinjection to assess biodistribution and tumor uptake characteristics. Qualitative and semiquantitative analyses were performed with statistical correlations on the physiologic organs of accumulation and HCC lesions for both tracers. [18F]FAC was obtained with 99% radiochemical purity, and the reaction yield was 16.0% with 1-hour synthesis time. The biodistribution of [18F]FAC on PET/CT was significantly different from that of [11C]ACT (p < .05) by the lack of preferential uptake in any specific organ, particularly the pancreas, resembling the pattern of blood-pool retention although partly metabolized via the bowel. There was no significant defluorination, and none of the [11C]ACT-avid HCC lesions showed increased [18F]FAC activity. These were different from the results reported on other species. [18F]FAC may not be a potential alternative tracer for [11C]ACT in PET/CT evaluation of HCC in human subjects.     

3,4,6-Tri-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranosyl phenylthiosulfonate: a thiol-reactive agent for the chemoselective 18F-glycosylation of peptides

3,4,5-Tri-O-acetyl-2-[18F]fluoro-2-deoxy-d-glucopyranosyl 1-phenylthiosulfonate (Ac3-[18F]FGlc-PTS) was developed as a thiol-reactive labeling reagent for the site-specific 18F-glycosylation of peptides. Taking advantage of highly accessible 1,3,4,6-tetra-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranose, a three-step radiochemical pathway was investigated and optimized, providing Ac3-[18F]FGlc-PTS in a radiochemical yield of about 33% in 90 min (decay-corrected and based on starting [18F]fluoride). Ac3-[18F]FGlc-PTS was reacted with the model pentapeptide CAKAY, confirming chemoselectivity and excellent conjugation yields of >90% under mild reaction conditions. The optimized method was adopted to the 18F-glycosylation of the alphavbeta3-affine peptide c(RGDfC), achieving high conjugation yields (95%, decay-corrected). The alphavbeta3 binding affinity of the glycosylated c(RGDfC) remained uninfluenced as determined by competition binding studies versus 125I-echistatin using both isolated alphavbeta3 and human umbilical vein endothelial cells (Ki = 68 +/- 10 nM (alphavbeta3) versus Ki = 77 +/- 4 nM (HUVEC)). The whole radiosynthetic procedure, including the preparation of the 18F-glycosylating reagent Ac3-[18F]FGlc-PTS, peptide ligation, and final HPLC purification, provided a decay-uncorrected radiochemical yield of 13% after a total synthesis time of 130 min. Ac3-[18F]FGlc-PTS represents a novel 18F-labeling reagent for the mild chemoselective 18F-glycosylation of peptides indicating its potential for the design and development of 18F-labeled bioactive S-glycopeptides suitable to study their pharmacokinetics in vivo by positron emission tomography (PET).     

Current and future anatomical and functional imaging approaches to pheochromocytoma and paraganglioma

After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging modalities. These include computed tomography, magnetic resonance imaging, single-photon emission computed tomography (SPECT) using 123I-metaiodobenzylguanidine or 111In-DTPA-pentetreotide, and positron emission tomography (PET) using 6-[18F]-fluorodopamine (18F-FDA), 6-[18F]-fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA), and 2-[18F]-fluoro-2-deoxy-d-glucose. We review the currently available data on the performance of anatomical imaging, SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic head and neck paragangliomas. We show that there appears to be no 'gold-standard' imaging technique for all patients with (suspected) PPGL. A tailor-made approach is warranted, guided by clinical, biochemical, and genetic characteristics. In the current era of a growing number of PET tracers, PPGL imaging has moved beyond tumor localization towards functional characterization of tumors.     

Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups

Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the (18)F-labeling of peptides for quantitative receptor imaging using positron emission tomography (PET). In this study, we extend the toolbox of oxime chemistry to include the novel prosthetic groups [(18)F]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [(18)F]5, and [(18)F]-4-(3-fluoropropoxy)benzaldehyde, [(18)F]9, in addition to the widely used 4-[(18)F]fluorobenzaldehyde, [(18)F]12. The three (18)F-aldehydes were conjugated to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group on biodistribution and tumor uptake studied in mice. The peptide conjugate [(18)F]7 was found to possess superior in vivo pharmacokinetics with higher tumor to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either [(18)F]10 or [(18)F]13. The radioactivity from the [(18)F]7 conjugate excreted more extensively through the kidney route with 79%id passing through the urine and bladder at the 2 h time point compared to around 55%id for the more hydrophobic conjugates [(18)F]10 and [(18)F]13. The chemical nature of a prosthetic group can be employed to tailor the overall biodistribution profile of the radiotracer. In this example, the hydrophilic nature of the ethylene glycol containing prosthetic group [(18)F]5 clearly influences the overall excretion pattern for the RGD peptide conjugate.     

Synthesis and evaluation of a [18F]formyl–Met–Leu–Phe derivative: A positron emission tomography imaging probe for bacterial infections

The tripeptide formyl–Met–Leu–Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an ¹⁸F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X?=?Nle) has a high affinity for FPR (Ki?=?0.62?±?0.13?nM). The radiochemical yield and purity of [¹⁸F]fMLFXYk(FB)k were 16% and >96%, respectively. The in vivo biodistribution study showed that [¹⁸F]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-to-muscle ratio of 4.6 at 60?min after [¹⁸F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [¹⁸F]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60?min after injection.     

Preparation of 18F-human serum albumin: a simple and efficient protein labeling method with 18F using a hydrazone-formation method

18F-labeling of proteins and peptides is important for positron emission tomography (PET). Although there are many methods for the labeling of proteins with (18)F, most of these are characterized by complicated procedures or low yields. Here, we report a novel and simple method which includes the preparation of [18F]fluorobenzaldehyde ([18F]FBA) and successive conjugation with hydrazinonicotinic acid-human serum albumin conjugate (HYNIC-HSA) via hydrazone formation. HYNIC-HSA, which can also be used for labeling with (99m)Tc, was prepared via reaction with N-hydroxysuccinimide (NHS) or tetrafluorophenyl (TFP) esters of HYNIC with HSA. No-carrier-added [18F]FBA was prepared by the nucleophilic substitution of [18F]fluoride to 4-trimethylammonium benzaldehyde triflate in the presence of tetrabutylammonium bicarbonate. [18F]FBA was purified by passing ion exchange cartridges (IC-H and QMA) and was adsorbed to a C18 Sep-Pak cartridge. The adsorbed [18F]FBA was then eluted with 50% ethanol. HYNIC-HSA was added to the solution and conjugated with [18F]FBA via hydrazone formation. 18F-HSA was purified with a PD10 column. Biodistribution of 18F-HSA, (99m)Tc-HSA, and [18F]FBA in mice were investigated at 10, 20, and 60 min after intravenous injection. The number of conjugated HYNIC molecules per HSA ranged from 5.2 to 23.2 depending on the reaction conditions. The labeling efficiency of 18F-FBA was 67 +/- 15.7%. The radiochemical purity after purification was over 99%. The conjugation efficiency of HYNIC-HSA with [18F]FBA was between 25% and 90%. The conjugation efficiency was observed to increase with increases in the number of conjugated HYNIC, the HYNIC-HSA concentration, or temperature. 18F-HSA exhibited a biodistribution pattern similar to that of (99m)Tc-HSA while [18F]FBA showed much lower blood activity than that of 18F-HSA and (99m)Tc-HSA. We concluded that 18F-HSA was successfully labeled using a novel method which involves hydrazone formation between [18F]FBA and HYNIC-HSA. This method can be applied to the 18F-labeling of other proteins or peptides.     

Aromatic radiofluorination and biological evaluation of 2-aryl-6-[18F]fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques

To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in radiolabeled form as an Aβ plaques-specific positron emission tomography (PET) imaging probe, we investigated synthetic route suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t(1/2)=110min) and diaryliodonium tosylate precursors (12, 13a-e and 14). 2-Aryl-6-[(18)F]fluorobenzothiazoles ([(18)F]1-3) were synthesized in efficiently short reaction times (40-60min) with high radiochemical yields (19-40%), purities (>95%) and specific activities (85-118GBq/μmol). Tissue distribution studies showed that high radioactivity of [(18)F]2 accumulated in the brain with rapid clearance in healthy mice. Radioactive metabolites were analyzed in brain samples of mice and corresponded to 81% of parent remained by 30min after a tail-vein injection. These results suggest that [(18)F]2 is a promising probe for evaluation of Aβ plaques imaging in brain using PET.     

Aspects of positron emission tomography radiochemistry as relevant for food chemistry

Summary. Positron emission tomography (PET) is a medical imaging technique using compounds labelled with short-lived positron emitting radioisotopes to obtain functional information of physiological, biochemical and pharmacological processes in vivo. The need to understand the potential link between the ingestion of individual dietary agents and the effect of health promotion or health risk requires the exact metabolic characterization of food ingredients in vivo. This exciting but rather new research field of PET would provide new insights and perspectives on food chemistry by assessing quantitative information on pharmocokinetics and pharmacodynamics of food ingredients and dietary agents. To fully exploit PET technology in food chemistry appropriately radiolabelled compounds as relevant for food sciences are needed. The most widely used short-lived positron emitters are ¹¹C (t_1/2 = 20.4 min) and ¹⁸F (t_1/2 = 109.8 min). Longer-lived radioisotopes are available by using ⁷⁶Br (t_1/2 = 16.2 h) and ¹²⁴I (t_1/2 = 4.12 d). The present review article tries to discuss some aspects for the radiolabelling of food ingredients and dietary agents either by means of isotopic labelling with ¹¹C or via prosthetic group labelling approaches using the positron emitting halogens ¹⁸F, ⁷⁶Br and ¹²⁴I.