[en] Reaction of N-(de-cyclopropylmethyl)diprenorphine with [1-¹¹C]cyclopropanecarbonyl chloride, itself prepared from cyclotron-produced [¹¹C]carbon dioxide, followed by reduction with LiAlH₄, provides a fast and efficient route to carbon-11 labelled diprenorphine, a new radioligand for the study of the opiate receptor system in vivo. (author)

[en] [¹⁸F]fluoride was produced via the ¹⁸O(p,n)¹⁸F reaction with a circulating 20% enriched [¹⁸O]water target. Parameters affecting the production yield of [¹⁸F]fluoride such as beam current, beam profile, irradiation time, target thickness, circulation rate, and window material were investigated and optimized. With a 20 μA irradiation of 2.5 mL [¹⁸O] water circulated at a flow rate of over 35 mL/min, a [¹⁸F]fluoride yield of more than 70% was obtained when the beam was defocussed and wobbled to get a uniform beam profile. In addition, radiolytically produced gases were recombined using a Pd catalyst into the target. (author)

[en] This paper is concerned with the use of positron emission tomography for functional imaging with an emphasis on quantification. The aim is to measure selective biological properties of a tumour and to differentiate between the tumour's biology and that of the normal surrounding tissue. The goal is to exploit these biological differences for therapeutic gain. In addition, it is of interest to measure functional changes in a tumour during a course of treatment. This might provide information on the mechanism of cure and suggest additional strategies for enhancing therapeutic efficacy. Furthermore, a direct measurement of a tumour's biological function could provide an objective way to asses the efficacy of a particular treatment regime. (author)

[en] Two generic radiosynthetic routes for the preparation of [¹¹C-carbonyl]isocyanates have been developed. Reaction of N-organo-sulfinylamines; RNSO, (R=Me, Et, allyl, cyclohexyl and phenyl) with [¹¹C]phosgene gave the corresponding [¹¹C-carbonyl]isocyanates in good radiochemical yield (53-68%) from [¹¹C]phosgene (decay corrected) in ca 16 min from EOB. Alternatively, the reaction of [¹¹C]phosgene with N,N'-organo-ureas; (RNH)₂CO, (R=Me, Et, Pr and phenyl) also gave the corresponding [¹¹C-carbonyl]isocyanates in moderate radiochemical yield (9-37%) from [¹¹C]phosgene (decay corrected) in ca 16 min from EOB. For identification, the [¹¹C-carbonyl]organo-isocyanates were derivatized with 1-(2-methoxyphenyl)piperazine in situ to [¹¹C-carbonyl]carboxamides and the position of radiolabelling in the carbonyl group confirmed by [^11/13C]co-labeling and subsequent carbon-13 NMR spectroscopy

[en] The potential antibody directed prodrug therapy half-mustard prodrug 4-[(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl-L-glutamic acid was synthesised by reductive alkylation of 4-[(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid using acetaldehyde. 4-[(2-chloroethyl)[¹¹C](2-ethyl)amino]phenoxycarbonyl-L-glutamic acid was synthesized with 18-22% decay corrected radiochemical yield in 45 min from EOB by reductive alkylation of 4-[(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid using [¹¹C]acetaldehyde. [¹¹C]Acetaldehyde was prepared in 60% decay corrected radiochemical yield by oxidation of [¹¹C]ethanol over heated copper oxide. The radiosynthesis of [¹¹C]ethanol was re-examined and optimized. 4-[(2-chloroethyl)(2-ethyl)amino]-phenoxycarbonyl-L-glutamic acid was found to have affinity for carboxypeptidase G2; the K_m and V_max were 99.4-115.9 μM (n=3) and 3.6-5.0 μM/min, respectively, at a carboxypeptidase G2 concentration of 0.0247 U/ml

[en] Annexin-V is a calcium-dependent protein that binds with high affinity to phosphaditylserine exposed during apoptosis. The aim of this study was to radiolabel annexin-V with iodine-124 for use as a potential probe of apoptosis by positron emission tomography. Annexin-V was radioiodinated directly using the cyclotron-produced positron emitter iodine-124 by the chloramine-T (CAT) method and indirectly by the pre-labelled reagent N-succinimidyl 3-[¹²⁴I]iodobenzoate ([¹²⁴I]m-SIB). Some reaction parameters of the CAT method such as reaction time and pH were optimised to give radiochemical yields of 22.3±2.6% (n=3, gel-filtration). After incubation with [¹²⁴I]m-SIB, radiolabelled annexin-V was obtained in 14% and 25% yield by FPLC and gel-filtration, respectively. The radiochemical purities from direct and indirect labelling were 97.7±1.0% (n=3) and 96.7±2.1% (n=3), respectively. The new radiotracers could be stored for up to four days without significant de-iodination. The biological activity of radiolabelled annexin-V was tested in control and camptothecin-treated (i.e. apoptotic) human leukaemic HL60 cells. A significantly higher (21%) binding in treated cells was observed with [¹²⁵I]m-SIB-annexin-V. The binding of [¹²⁵I]m-SIB labelled annexin-V to camptothecin treated cells was blocked (68%) by a 100-fold excess of unlabelled annexin-V. Abbreviations: Fast protein liquid chromatography (FPLC), Instant thin layer chromatography (ITLC), Sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), 3-iodobenzoate (m-IBA), N-succinimidyl 3-(trimethylstannyl)benzoate (m-MeATE)

[en] 2-[¹¹C]Thymidine has been produced from [¹¹C]methane via [¹¹C]phosgene and [¹¹C]urea. Anhydrous [¹¹C]urea was prepared from [¹¹C]phosgene by reaction with liquid ammonia. This novel approach avoids the problems associated with the synthesis of anhydrous [¹¹C]urea from [¹¹C]cyanide. A fully automated system based on a modular approach and under PLC control has been developed. The system provides 2-[¹¹C]thymidine reliably and reproducibly for clinical PET studies. The radiosynthesis takes 45-50 min from [¹¹C]methane and the average yield was 1.5-3.3 GBq (40-90 mCi). The specific radioactivity was typically in the range 29.6-51.8 GBq μmol^-1 (0.8-1.4 Ci μmol^-1) at EOS corresponding to 6-12 μg of stable thymidine. The radiochemical yield of 2-[¹¹C]thymidine was ca. 14% from [¹¹C]methane

[en] The cocaine analogue RTI-121 (3β-(4-iodophenyl)tropane-2β-carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [¹¹C]RTI-55 (2↔-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5-HT uptake site. The results indicate that [¹¹C]RTI-121 could be used in preference to [¹¹C]RTI-55 in man. Experimentally, [¹¹C]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography

[en] The aim of this study was to investigate the role of thymidine kinase 1 (TK₁) protein in 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) studies. We investigated the in vivo kinetics of [¹⁸F]FLT in TK₁+/- and TK₁-/- L5178Y mouse lymphoma tumours that express different levels of TK₁ protein. [¹⁸F]FLT-derived radioactivity, measured by a dedicated small animal PET scanner, increased within the tumours over 60 min. The area under the normalised tumour time-activity curve were significantly higher for the TK₁+/- compared with the -/- variant (0.89±0.02 vs 0.79±0.03 MBq ml^-1 min, P=0.043; n=5 for each tumour type). Ex vivo gamma counting of tissues excised at 60 min p.i. (n=8) also revealed significantly higher tumour [¹⁸F]FLT uptake for the TK₁+/- variant (6.2±0.6 vs 4.6±0.4%ID g^-1, P=0.018). The observed differences between the cell lines with respect to [¹⁸F]FLT uptake were in keeping with a 48% higher TK₁ protein in the TK₁+/- tumours versus the -/- variant (P=0.043). On average, there were no differences in ATP levels between the two tumour variants (P=1.00). A positive correlation between [¹⁸F]FLT accumulation and TK₁ protein levels (r=0.68, P=0.046) was seen. Normalisation of the data for ATP content further improved the correlation (r=0.86, P=0.003). This study shows that in vivo [¹⁸F]FLT kinetics depend on TK₁ protein expression. ATP may be important in realising this effect. Thus, [¹⁸F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring. (orig.)