Automated synthesis of hypoxia imaging agent [18F]FMISO based upon a modified Explora FDG4 module

A new automated synthesis procedure of 1-H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO), a specific hypoxia imaging agent with great significances for the noninvasive, dynamic hypoxia evaluation of cancer, was developed by modifying Explora FDG₄ module, a commercial [¹⁸F]FDG production system, in this study. Its radiochemical synthesis was carried out via two sequent reaction steps, i.e. the nucleophilic displacement of labeling precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) with activated ¹⁸F- ion at 100 °C for 8 minutes, and the following hydrolysis with 1M HCl at 100 °C for 5 minutes and neutralization with 1M NaOH. Two-pot reaction with two independent separations was adopted to assure the good separation of final product via solid phase extraction (SPE) based upon combined Sep-pak cartridges instead of high performance liquid chromatography (HPLC). This fast, reliable preparation route of ¹⁸F-FMISO could complete within 50 minutes with about 55% of high radiochemical yield (with decay correction) and more than 98% of good radiochemical purity. The modified module could perform multiple runs of production of [¹⁸F]FMISO.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-[2-[<Superscript>18</Superscript>F]fluoro-3-(2-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazole-1-yl)propyl]tyrosine ([<Superscript>18</Superscript>F]FNT]) as a new class of tracer for imaging hypoxia

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([¹⁸F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl)-2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 °C. At the end of radiosynthesis, [¹⁸F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia.     

Automated synthesis of [18F]FMISO on IBA Synthera®

In cancer cells hypoxia can cause resistance to both radio- and chemo-therapy. Being able to quantify, the degree of hypoxia in the cells is a useful tool in therapy planning. The positron emitting 1-[¹⁸F]fluoro-3-(2-nitro-1H-imidazol-1-yl)propan-2-ol ([¹⁸F]FMISO) is the most extensively used tracer for imaging hypoxia. Automated synthesis of [¹⁸F]FMISO was set up on IBA Synthera^®. The precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-p-toluenesulfonyl propanediol (NITTP) was heated at 100 °C for 10 min with [K/K 2.2.2.]⁺[¹⁸F]^? and thereafter hydrolyzed with 0.1 M hydrochloric acid at 90 °C for 2 min. Purification was performed on solid-phase extraction (SPE) cartridges. [¹⁸F]FMISO was obtained in 50 ± 3 % (n = 6) radiochemical yield (decay-corrected) in 35 min synthesis time with radiochemical purity of ≥98 %. The use of disposable Integrated Fluid Processors (IFP?:s) and cartridge purification simplifies the handling and shortens the synthesis time. This is a no frills setup based on all commercially available materials and the synthesis is performed with minor changes from the FDG time-list.     

Nucleophilic aromatic substitution by [<Superscript>18</Superscript>F]fluoride at substituted 2-nitropyridines

For the radiofluorination of benzenes and benzene derivatives, the electrophilic reaction with [¹⁸F]F₂ is a very common route. Yet, aromatic nucleophilic substitution (S_NAr) by n.c.a [¹⁸F]fluoride, which can be produced efficiently in high amounts, has been considered to be very desirable. However, to facilitate ¹⁸F-labelling via S_NAr at an electron rich aromatic system, an appropriate leaving group must be present together with an auxiliary group in ortho or para position to the leaving group. An interesting alternative for the auxiliary group is the heteroatom of a heteroaromatic system, for which pyridine is a leading example. Dolci et al. (J Label Compd Radiopharm 42:975–985, 1999) have evaluated the scope of the nucleophilic aromatic fluorination of 2-substituted pyridine rings using the activated K [¹⁸F]F-K₂₂₂ complex. As methyl and methoxy groups are known to enhance the electron density of an aromatic system by the +I and the +M effect, respectively, S_NAr is unlikely to occur. Until now, the effect of these substituents has not been studied towards the ¹⁸F-radiofluorination of substituted 2-nitropyridines by use of [¹⁸F]fluoride. Therefore, we have investigated the effect of methoxy and methyl groups in 2-nitropyridines. The results showed that 3-methoxy-2-nitropyridine and 3-methyl-2-nitropyridine can efficiently be substituted by [¹⁸F]fluoride with high RCY’s (70–89%) in short reaction times (1–30 min) at a reaction temperature of 140 °C. Moreover, 3-methoxy-6-methyl-2-[¹⁸F]fluoropyridine was obtained from the corresponding nitro-precursor in a high yield of 81 ± 1% after 30 min at 140 °C. In case of 2-nitropyridines data indicates the effect of methyl and methoxy groups on S_NAr to be of minor importance.     

Fully automated and simplified radiosynthesis of [<Superscript>18</Superscript>F]-3′-deoxy-3′-fluorothymidine using anhydro precursor and single neutral alumina column purification

[¹⁸F]-3′-deoxy-3′-fluorothymidine ([¹⁸F]FLT) is an established positron emission tomograph (PET)—radiopharmaceutical to study cell-proliferation rate in tumors. Very low practical yield, uncertain and time-consuming high performance liquid chromatography (HPLC) purification, are the main obstacles for the routine use of [¹⁸F]FLT in clinical PET. To obviate these difficulties, we have developed a fully automated radiosynthesis procedure for [¹⁸F]FLT using 5′-O-(4,4′-dimethoxytriphenylmethyl)-2,3′-anhydro-thymidine (DMTThy) and simplified single neutral alumina column purification. The [¹⁸F]FLT yield was 8.48 ± 0.93% (n = 5) (without radioactive decay correction) in a synthesis time of 68 ± 3 min. The radiochemical purity was greater than 95% as confirmed by analytical HPLC using reference standard FLT and also free of non-radioactive impurity. Soluble aluminum in the final product was much below the permissible limits. Di-methyl sulfoxide (DMSO), the reaction medium, could be detected in the final product in trace amounts, well below the permissible levels. The synthesized [¹⁸F]FLT was sterile and bacterial endotoxin free by appropriate tests. PET imaging study in normal rabbits showed distinct localization of [¹⁸F]FLT in organs having rapid cell division rate like bone marrow, guts and snout and the excretion was through the renal route. There were no significant uptakes in bone and brain. The former finding confirms the in vivo stability of the [¹⁸F]FLT. This simplified radiosynthesis procedure can easily be adapted in any commercial or indigenous [¹⁸F]FDG synthesis module for routine [¹⁸F]FLT synthesis without the need of additional automation for HPLC purification.     

Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters

The dependence of the radiochemical yield of [¹⁸F]fluoromisonidazole (1) on different reaction parameters such as reaction time, temperature and amount of precursor was investigated for the nucleophilic substitution of tosylate by [¹⁸F]fluoride and subsequent hydrolysis of the protecting group on 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonylpropanediol as the precursor molecule (2). Highest yields (86%±6%) were obtained using 10 mg (2) at 100°C for 10 minutes, whereas both at 80 and 120°C the yields were lower (46%±11% and 29%±14%, respectively). A rapid decrease of the yield was observed when the reaction time exceeded 15 minutes, i.e., at 100°C using 5 mg (2) the radiochemical yield decreased from 61%±8% at 15 minutes to 18%±10% at 60 minutes.     

Synthesis of 15-(4-[<Superscript>131</Superscript>I]iodophenyl)pentadecanoic acid (<Emphasis Type="Italic">p</Emphasis>-IPPA) via tin-precursor using Chloramine-T as an oxidant

A rapid method for the preparation of the radioiodinated 15-(4-iodophenyl)pentadecanoic acid (p-IPPA) was developed. ¹³¹I-p-IPPA was obtained from the corresponding tin precursor and ¹³¹I-iodide using Chloramine-T as an oxidant in a radiochemical yield of 90 ± 1.4% with a radiochemical purity > 99% when performing the labeling at room temperature within a reaction time of 3 min. The study of dependences on temperature (0, 20 and 80 °C) and reaction time (1, 3, 5, 10 and 30 min) showed no yield increase with higher temperatures and prolonged reaction times but the formation of side products.     

Radiofluorination of 2-fluoropyridines by isotopic exchange with [<Superscript>18</Superscript>F]fluoride

In homoaromatic systems, isotopic exchange (¹⁸F/¹⁹F) was previously (J Label Compd Radiopharm 18(12):1721–1730 [2], J Chem Soc Perkin Trans 1(3):295–298 [3]) proven to be advantageous, yet in general specific activity is thought to be low. For heteroaromatic systems, in particular, very few examples are published regarding the ¹⁸F-labelling of 2-substituted pyridines (J Label Compd Radiopharm 42:975–985 [9]). Therefore, in 2-fluoropyridines, we decided to study the ¹⁸F labelling by isotopic exchange (¹⁸F/¹⁹F). The radiochemical yield for 2-fluoropyridine was 90 ± 2%. Even if 2-fluoropyridine was substituted by an electron-donating group such as a methyl or a methoxy group, radiochemical yields were 80 ± 1 and 78 ± 1%, respectively. Although in benzenes, these substituents are known to decrease nucleophilic substitutions by ¹⁸F-Fluoride significantly. Moreover, by choosing appropriate concentrations of 2-fluoropyridines, reasonably high specific activities up to 10 GBq/μmol were obtained.     

Synthesis,radiochemical and biological characteristics of <Superscript>99m</Superscript>Tc-8-hydroxy-7-substituted quinoline complex: a novel agent for infection imaging

2,2′-[(8-hydroxyquinolin-7-yl)methylazanediyl]diacetic acid (HQMADA) was synthesized via reaction of 8-hydroxyquinoline with iminodiacetic acid in presence of paraformaldehyde with a yield of 27%. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m in pertechnetate form (^99mTcO₄ ⁻) in the presence of stannous chloride dihydrate was carried out via chelation reaction. The reaction parameters that affect the labeling yield such as HQMADA concentration, stannous chloride dihydrate concentration, pH of the reaction mixture, and reaction time were studied to optimize the labeling conditions. Maximum radiochemical yield of ^99mTc-HQMADA complex (91.9%) was obtained by using 1.5 mg HQMADA, 50 μg SnCl₂·2H₂O, pH 8 and 30 min reaction time. Biodistribution studies in mice were carried out in experimentally induced infection in the left thigh using E. coli. ^99mTc-HQMADA complex showed higher uptake (T/NT = 5.5 ± 0.3) in the infectious lesion than the commercially available ^99mTc-ciprofloxacin (T/NT = 3.8 ± 0.8). Biodistribution studies for ^99mTc-HQMADA complex in Albino mice bearing septic and aseptic inflammation models showed that ^99mTc-HQMADA complex able to differentiate between septic and aseptic inflammation.     

Autoradiolysis of the 2-deoxy-2-[<Superscript>18</Superscript>F]fluoro-D-glucose radiopharmaceutical

Summary To control virtually the toxic compounds and to improve quality control of the solution of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (2-[¹⁸F]FDG), the products of its autoradiolysis were analyzed by high-performance liquid chromatography with electrospray mass spectrometric and radiometric detectors (HPLC/MS/RAD), thin layer chromatography on TLC silica plate and HPTLC on amino modified silica plate. Except Kryptofix^™ 2.2.2, glucose and fluoride anion, no by-products and impurities were observed by LC/MS analysis of fresh 2-[¹⁸F]FDG samples. The analysis performed in the time interval of 6 to 48 hours after the end of 2-[¹⁸F]FDG synthesis indicated that the activity of the autoradiolysis products separated by HPLC did not exceed 1.3%. As the main autoradiolysis products of 3.3 ^. 10^-5 to 4.4 ^. 10^-5M 2-[¹⁸F]FDG solution of original specific activity 0.5-1.5 GBq ^. cm^-3 were established: arabinose - 2.8 μM (G= 0.07/100 eV), gluconic and glucuronic acids 1.8-0.5 μM (G =0.01-0.05/100 eV), arabinose and araburonic acids occurred under 0.5 μM concentration at residual glucose contents about 0.14 mM. Radiation chemical yields of active products were calculated from molar activity of 2-[¹⁸F]FDG and the percentage of their activity: 0.5% radiochemical yield of 2-[¹⁸F]fluoroglucuronic acid corresponds to the G = 0.004/100 eV and 0.3% yield of 2-[¹⁸F]fluorogluconic acid issues G = 0.003/100 eV.     

Radiosynthesis and preliminary biological evaluation of the 2-[<Superscript>18</Superscript>F]fluoropropionic acid enantiomers for tumor PET imaging

The aim of this study was to synthesize the optically pure [¹⁸F]FPA, and to investigate the diagnostic value of different isomers. Semi-automated radiosynthesis of R-[¹⁸F]FPA or S-[¹⁸F]FPA was respectively from the chiral precursor (S)- or (R)-ethyl 2-(((trifluoromethyl)sulfonyl)oxy)propanoate via a two-step reaction and performed on the commercial FDG synthesizer. The improved radiochemical yields of R-[¹⁸F]FPA and S-[¹⁸F]FPA were 30–40% (decay-uncorrected, n = 10) in 35 min. There was no significant difference on the biodistribution of two enantiomers in normal mice (P > 0.05), but positron emission tomography imaging demonstrated that R-[¹⁸F]FPA was more suitable for PC3 tumor imaging than S-[¹⁸F]FPA and [¹⁸F]FDG.     

One-step conjugation of glycylglycine with [<Superscript>18</Superscript>F]FDG and a pilot PET imaging study

This study describes a single step conjugation of Glycylglycine (GlyGly) which is a small peptide, with [¹⁸F]FDG via oxime formation. Amiooxy-functionalization of GlyGly (AO-GlyGly) was accomplished through the reaction of Boc-aminooxy succinimide ester. Conjugation reaction was performed at 100 °C for 30 min in a vial containing AO-GlyGly and [¹⁸F]FDG solution. The radiolabeled product ([¹⁸F]FDG-GlyGly) was obtained with 98.65?±?0.35% yield without any purification step which makes this method more attractive for ¹⁸F radiolabeling. The present study is concluded with an in vivo pilot animal PET study to assess biodistribution and kinetics of chemoselectively [¹⁸F]FDG tagged GlyGly in vivo.     

Cyclotron production of <Superscript>169</Superscript>Yb: a potential radiolanthanide for brachytherapy

In the present study, ytterbium-169 was produced via the ¹⁶⁹Tm(p, n)¹⁶⁹Yb nuclear process at the AMIRS (Cyclone-30, IBA, Belgium) cyclotron, irradiating Tm₂O₃ with proton particles of 15 MeV primary energy and 20 μA current for 20 min. Deposition of Tm₂O₃ on Cu substrate was carried out via by the sedimentation method. The 543 mg of thulium(III)oxide with 108 mg of ethyl cellulose and 8 mL of acetone were used to prepare a Tm₂O₃ layer of 11.69 cm². Yields of about 0.643 MBq ¹⁶⁹Yb per μAh were experimentally obtained. ¹⁶⁹Yb was separated in 80 ± 5% radiochemical yield using liquid–liquid extraction. Solvent extraction of no-carrier-added ¹⁶⁹Yb from irradiated thulium(III)oxide target hydrochloric solution was investigated using di-(2-ethylhexyl)phosphoric acid (HDEHP).     

Metabolite analysis of [<Superscript>18</Superscript>F]Florbetaben (BAY 94-9172) in human subjects: a substudy within a proof of mechanism clinical trial

[¹⁸F]Florbetaben ([¹⁸F]BAY 94-9172) is a promising β-amyloid (Aβ) targeted PET-tracer currently in late stage clinical development. [¹⁸F]Florbetaben can assist in the more accurate diagnosis of Alzheimer’s Disease (AD) by non-invasive, in vivo detection of Aβ in the brain. To determine the arterial input function of the PET tracer—as part of a proof of mechanism (PoM) study—arterial samples were drawn from all subjects at predefined time points post injection (p.i.), and the proportion of unchanged tracer [¹⁸F]Florbetaben was determined by HPLC analysis. Plasma metabolite profiles were investigated following intravenous administration of 300 MBq (±60 MBq) of [¹⁸F]Florbetaben to both, patients with AD and healthy controls (HCs), and various methods for processing the blood samples were evaluated. Addition of acetonitrile to plasma samples (obtained from whole blood by centrifugation) and precipitation of proteins resulted in a recovery of more than 90% of the initial radioactivity in the supernatants. High Performance Liquid Chromatography using a polymer-based column (PRP-1) in conjunction with gradient elution was found to be a suitable method of metabolite analysis of [¹⁸F]Florbetaben. HPLC analyses indicated that [¹⁸F]Florbetaben is rapidly metabolized in vivo with an estimated initial half-life of about 6 min. A polar metabolite fraction, consisting presumably of more than one component, and (to a smaller extent) of the demethylated derivative of [¹⁸F]Florbetaben were time-dependently detected in plasma.     

Preparation and biodistribution of [<Superscript>131</Superscript>I]linezolid in animal model infection and inflammation

Linezolid is the first of new class of antibiotics, the oxazolidinones, and exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Aim of the study: Linezolid was to label with I-131 and potential of the radiolabeled antibiotic was to investigate in inflamed rats with S. aureus (S. aureus) and sterile inflamed rats with turpentine oil. Linezolid was labeled with I-131 by iodogen method. Biodistribution of [¹³¹I]linezolid was carried out in bacterial inflamed and sterile inflamed rats. Radiolabeling yield of [¹³¹I]linezolid was determined as 85 ± 1% at pH 2. After injecting of [¹³¹I]linezolid into bacterial inflamed and sterile inflamed rats, radiolabeled linezolid was rapidly removed from the circulation via the kidneys. Binding of [¹³¹I]linezolid to bacterial inflamed muscle (T/NT = 77.48 at 30 min) was five times higher than binding to sterile inflamed muscle (T/NT = 14.87 at 30 min) of rats. [¹³¹I]linezolid showed good localization in bacterial inflamed tissue. It was demonstrated that [¹³¹I]linezolid can be used to detect S. aureus inflammation in rats.     

Preparation and preliminary evaluation of [<Superscript>67</Superscript>Ga]-tetra phenyl porphyrin complexes as possible imaging agents

[⁶⁷Ga]labeled tetraphenyl porphyrin ([⁶⁷Ga]-TPP) was prepared using freshly prepared [⁶⁷Ga]GaCl₃ and tetraphenyl porphyrin (TPPH₂) for 30–60 min at 25 °C (radiochemical purity: >97 ± 1% ITLC, >98 ± 0.5% HPLC, specific activity: 13–14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 24 h. The partition coefficient was calculated for the compound (log P 1.89). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT imaging up to 24 h. A detailed comparative pharmacokinetic study performed for ⁶⁷Ga cation and [⁶⁷Ga]-TPP. The complex is mostly washed out from the circulation through kidneys and can be an interesting tumor imaging/targeting agent due to low liver uptake and rapid excretion through the urinary tract.     

Preparation of <Superscript>99m</Superscript>Tc-PQQ and preliminary biological evaluation for the NMDA receptor

Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator and nerve growth factor found in a class of enzymes called quinoproteins, was labeled with ^99mTc by using stannous fluoride (SnF₂) method. Radiolabeling qualification, quality control and characterization of ^99mTc-PQQ and its biodistribution studies in mice were performed and discussed. Effects of pH values, temperature, time and reducing agents concentration on the radiolabeling yield were investigated. The quality control procedure of ^99mTc-PQQ was determined by thin layer chromatography (TLC), radio high-performance liquid chromatography (RHPLC) and paper electrophoresis methods. The average radiolabeling yield was 94 ± 1% under optimum conditions of 0.99 mg of PQQ, 30 μg of SnF₂, 0.5 mg of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) and 18.5 MBq of Na^99mTcO₄ at pH 6 and 25 °C with a response volume of 1 ± 0.1 mL. ^99mTc-PQQ was stable and anionic. Lipid–water partition coefficient of ^99mTc-PQQ was −1.49 ± 0.16. The pharmacokinetics parameters of ^99mTc-PQQ were t _1/2α = 18.16 min, t _1/2β = 100.45 min, K ₁₂ = 0.013 min⁻¹, K ₂₁ = 0.017 min⁻¹, K _e = 0.016 min⁻¹, AUC (area under the curve) = 1040.78 ID% g⁻¹ min and CL (plasma clearance) = 0.096 mL min⁻¹. The dual-exponential equation was Y = 10.88e^−0.038t  + 5.21e^−0.0069t . The biodistribution of ^99mTc-PQQ was studied in ICR (Institute for Cancer Research 7701 Burhelme Are., Fox Chase, Philadelphia, PA 1911 USA) mice. In vitro autoradiographic studies clearly showed that the ^99mTc-PQQ radioactivity accumulated predominantly in the hippocampus and cortex, which had a high density of N-methyl-d-aspartate Receptor (NMDAR). The enrichment can be blocked by NMDAR redox modulatory site antagonists-ebselen (EB) and ^99mTc-PQQ is therefore a promising candidate for the molecular imaging of NMDAR. To date, however, there have been no studies characterizing ^99mTc-PQQ.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [¹⁸F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [¹⁸F]FET are similar to those of [¹⁸F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [¹⁸F]FDG. Autoradiography of [¹⁸F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) and the National Natural Science Foundation of China (Grant No. 30371634)     

Determination of HEPES in <Superscript>68</Superscript>Ga-labeled peptide solutions

A practical and reliable HPLC method was used for the determination of 2-[4-N-(2-hydroxyethyl)-1-piperazinyl]-N′-ethanesulfonic acid (HEPES) content in the ⁶⁸Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (DOTANOC). Linearity of this method was observed in a concentration range of 0.01–10 mg mL⁻¹ and the quantitative limit (signal to noise = 11) was determined as 10 μg mL⁻¹. The HEPES concentration in the final products of ⁶⁸Ga-DOTANOC was typically lower than the detection limit. Pure water and HEPES buffer as reaction medium were investigated using various activities of gallium-68. It was demonstrated that the presence of HEPES buffer consistently furnished very high radiochemical purity of ⁶⁸Ga-DOTANOC, which remained stable for several hours post-labeling. Evidence is provided that in addition to its role as a buffer, HEPES also functions as a radioprotectant agent.     

A perspective on <Superscript>99m</Superscript>Tc and <Superscript>125/131</Superscript>I labeled receptor targeted compounds and their in vitro/in vivo affinities

A novel quinoline derivative, 2,2′-[(5-chloro-8-hydroxyquinoline-7-yl) methylazanediyl] diacetic acid (CHQMADA) was labeled with ^99mTc using SnCl₂·2H₂O as a reducing agent to give a complex with a labeling yield 94 %. Also [^99mTc(H₂O)₃(CO)₃]⁺ was prepared by heating at 100 °C for 30 min using 2 mg CHQMADA at pH 8 to give a labeling yield >99 %. ^99mTc-(CO)₃ CHQMADA and ^99mTc-Sn(II)-CHQMADA showed tissue uptake (target to non target T/NT = 6.80 ± 0.22) and (T/NT = 5.65 ± 0.34) respectively in Escherichia coli induced infection, which is higher than the commercially available ^99mTc-ciprofloxacin (T/NT = 3.80 ± 0.80). In conclusion, both complexes were able to differentiate between septic and aseptic inflammation with superiority of [^99mTc-(CO)₃ CHQMADA].