Nuclear Medicine and Biology

Editorial Board

2012-05-01

Synthesis of oncological [11C]radiopharmaceuticals for clinical PET

2011-12-15

Abstract: Positron emission tomography (PET) is a nuclear medicine modality which provides quantitative images of biological processes in vivo at the molecular level. Several PET radiopharmaceuticals labeled with short-lived isotopes such as 18F and 11C were developed in order to trace specific cellular and molecular pathways with the aim of enhancing clinical applications. Among these [11C]radiopharmaceuticals are N-[11C]methyl-choline ([11C]choline), l-(S-methyl-[11C])methionine ([11C]methionine) and 1-[11C]acetate ([11C]acetate), which have gained an important role in oncology where the application of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) is suboptimal. Nevertheless, the production of these radiopharmaceuticals did not reach the same level of standardization as for [18F]FDG synthesis. This review describes the most recent developments in the synthesis of the above-mentioned [11C]radiopharmaceuticals aiming to increase the availability and hence the use of [11C]choline, [11C]methionine and [11C]acetate in clinical practice.

Bombesin analogues for gastrin-releasing peptide receptor imaging

2012-01-20

Abstract: Objectives: The present study describes the design and development of a series of new bombesin (BBN) antagonist peptide ligands of the form [64Cu-(NO2A-X-D-Phe6-BBN(6-13)NHEt)], where Cu-64=a positron emitting radiometal; NO2A=1,4,7-triazacyclononane-1,4-diacetic acid; X=6-amino hexanoic acid, 8-amino octanoic acid or 9-Aminononanoic acid; and BBN(6-13)NHEt=Gln-Trp-Ala-Val-Gly-His-Leu-NHEt, an antagonist analogue of bombesin peptide for specific targeting of the gastrin-releasing peptide receptor (GRPR).Methods: [NO2A-X-D-Phe6-BBN(6-13)NHEt] conjugates were manually conjugated with NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and the resulting conjugates were labeled with 64Cu to yield [64Cu-(NO2A-X-D-Phe6-BBN(6-13)NHEt)]. The metallated and nonmetallated conjugates were purified via reversed-phase high-performance liquid chromatography and characterized by electrospray ionization–mass spectrometry.Results: Competitive displacement binding assays displayed nanomolar binding affinities toward human GRPR for all of the newly formed peptide analogues. Biodistribution studies showed very high uptake and retention of tumor-associated radioactivity in PC-3 (a prostate tumor model known to express the GRPR) tumor-bearing rodent models. The radiolabeled conjugates also exhibited rapid urinary excretion and very high tumor to background ratios. Micro-positron emission tomography (PET) molecular imaging investigations showed clear visualization of tumors in female PC-3 tumor-bearing mice 15 h postinjection.Conclusion: The biodistribution and molecular imaging study suggests that these conjugates can be considered as potential PET tracer candidates for the diagnosis of GRPR-positive tumors in human patients.

Combined-modality radioimmunotherapy: synergistic effect of paclitaxel and additive effect of bevacizumab

2011-12-15

Abstract: Introduction: This study was undertaken to investigate the effect of paclitaxel and bevacizumab on the therapeutic efficacy of 90Y-labeled B3 monoclonal antibody, directed against Ley antigen, for the treatment of Ley-positive A431 tumors implanted subcutaneously in the right hind flank of nude mice.Methods: When the tumor size reached ∼200 mm3, the mice received a single dose of intravenous (iv) 90Y-labeled B3 (60 μCi/150 μg or 100 μCi/150 μg B3), intraperitoneal paclitaxel (40 mg/kg) or iv bevacizumab (5 mg/kg) for monotherapy. To investigate the effect of combined therapies on survival, the mice were treated with two or three agents in the following combinations: 90Y-B3 on day 0 and paclitaxel on day 1; bevacizumab on −1 day and 90Y-B3 on day 0; bevacizumab on −1 day and paclitaxel on day 1; bevacizumab, 90Y-B3 and paclitaxel each at 1-day intervals. The mice with no treatment were used as a control. The tumor volume at 1000 mm3 was used as a surrogate end point of survival.Results: Compared to control animals, paclitaxel delayed tumor growth with a significantly longer median survival time (P .10). Fluorescence microscopy analysis indicated that paclitaxel increased, whereas bevacizumab decreased, the accumulation and penetration of Alexa Fluor 647-B3 into tumor microenvironment compared to the control (P<.05).Conclusion: Our findings on the paclitaxel effect support a hypothesis that the increased tumor accumulation and penetration of 90Y-B3 as well as the high radiosensitization of tumor cells by paclitaxel may be the major factors responsible for the synergistic effect of the combined therapy involving 90Y-B3 with paclitaxel.

Preclinical studies of potential amyloid binding PET/SPECT ligands in Alzheimer's disease

Marie M. Svedberg, Obaidur Rahman, Håkan Hall — 2012-01-09

Abstract: Visualizing the neuropathological hallmarks amyloid plaques and neurofibrillary tangles of Alzheimer's disease in vivo using positron emission tomography (PET) or single photon emission computed tomography will be of great value in diagnosing the individual patient and will also help in our understanding of the disease. The successful introduction of [11C]PIB as a PET tracer for the amyloid plaques less than 10 years ago started an intensive research, and numerous new compounds for use in molecular imaging of the amyloid plaques have been developed. The candidates are based on dyes like thioflavin T, Congo red and chrysamine G, but also on other types such as benzoxazoles, curcumin and stilbenes. In the present review, we present methods of the radiochemistry and preclinical evaluation as well as the main properties of some of these compounds.

An allogenic site-specific rat model of bone metastases for nuclear medicine and experimental oncology

2011-12-15

Abstract: Bone metastases are a major problem in several tumor entities affecting the therapeutic decision and the patient's prognosis. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are promising techniques for identifying bone tumors using gamma- or positron-emitting labeled radiotracers, but the same tracers if labeled with beta-emitters may also be used to apply therapeutic radionuclides for localized irradiation. For the tracer development specifically accumulating in osseous lesions, animal models of bone metastasis are needed. A technique was developed for tumor cell injection into the circulation of the hind limb of rats. For tumor implantation, the arteria epigastrica caudalis superficialis (a branch of the femoral artery) was cannulated, and 2×105 cells were injected. By using the allogenic Walker 256 mammary carcinoma cell line, isolated bone metastases were induced. For visualizing of the tumor growth, PET with 18F-fluoride was performed weekly on a μ-PET system. After 2–3 weeks, tumor invasion was confirmed by histology. Three weeks after tumor cell inoculation, PET images showed signs of bone metastases in 9 out of 11 animals. The tumors were located either in the proximal tibia/fibula or in the distal femur. At this time, the animals showed no restrictions in mobility. The tumors grew constantly over time. The final histological analysis showed tumors growing invasively into the bone matrix. With this model, new SPECT or PET tracers can be evaluated for their potency of accumulating in bone metastases in vivo and to determine which are therefore suitable for diagnosis and/or therapy.

Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions

2011-12-15

Abstract: The DOTA macrocyclic ligand can form stable complexes with many cations besides yttrium and lutetium. For this reason, the presence of competing cationic metals in yttrium-90 and lutetium-177 chloride solutions can dramatically influence the radiolabeling yield. The aim of this study was to evaluate the coordination yield of yttrium- and lutetium-DOTATATE complexes when the reaction is performed in the presence of varying amounts of competing cationic impurities. In the first set of experiments, the preparation of the samples was performed by using natural yttrium and lutetium (20.4 nmol). The molar ratio between DOTATATE and these metals was 1 to 1. Metal competitors (Pb2+, Zn2+, Cu2+, Fe3+, Al3+, Ni2+, Co2+, Cr3+) were added separately to obtain samples with varying molar ratio with respect to yttrium or lutetium (0.1, 0.5, 1, 2 and 10). The final solutions were analyzed through ultra high-performance liquid chromatography with an UV detector. In the second set of experiments, an amount of 90Y or 177Lu chloride (6 MBq corresponding to 3.3 and 45 pmol, respectively) was added to the samples, and a radio-thin layer chromatography analysis was carried out. The coordination of Y3+ and Lu3+ was dramatically influenced by low levels of Zn2+, Cu2+ and Co2+. Pb2+ and Ni2+ were also shown to be strong competitors at higher concentrations. Fe3+ was expected to be a strong competitor, but the effect on the incorporation was only partly dependent on its concentration. Al3+ and Cr3+ did not compete with Y3+ and Lu3+ in the formation of DOTATATE complexes.

Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with 111In using a maleimido derivative of NODAGA

2011-12-15

Abstract: Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule.Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to ZHER2:2395 Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [111In-MMA-NODAGA-Cys61]-ZHER2:2395 were studied. Biodistribution of [111In-MMA-NODAGA-Cys61]-ZHER2:2395 and [111In-MMA-DOTA-Cys61]-ZHER2:2395 was compared in mice.Results: The affinity of [MMA-NODAGA-Cys61]-ZHER2:2395 binding to HER2 was 67 pM. The 111In-labeling yield was 99.6%±0.5% after 30 min at 60°C. [111In-MMA-NODAGA-Cys61]-ZHER2:2395 bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [111In-MMA-NODAGA-Cys61]-ZHER2:2395 in mice bearing DU-145 xenografts (4.7%±0.8% ID/g) was lower than uptake of [111In-MMA-DOTA-Cys61]-ZHER2:2395 (7.5%±1.6% ID/g). However, tumor-to-organ ratios were higher for [111In-MMA-NODAGA-Cys61]-ZHER2:2395 due to higher clearance rate from normal tissues.Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.

Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil

2012-01-09

Abstract: Objectives: (R)-[11C]verapamil is widely used as a positron emission tomography (PET) tracer to evaluate P-glycoprotein (P-gp) functionality at the blood–brain barrier in man. A disadvantage of (R)-[11C]verapamil is the fact that its main metabolite, [11C]D617, also enters the brain. For quantitative analysis of (R)-[11C]verapamil data, it has been assumed that the cerebral kinetics of (R)-[11C]verapamil and [11C]D617 are the same. The aim of the present study was to investigate whether the cerebral kinetics of (R)-[11C]verapamil and [11C]D617 are indeed similar and, if so, whether [11C]D617 itself could serve as an alternative PET tracer for P-gp.Methods: [11C]D617 was synthesized and its ex vivo biodistribution was investigated in male rats at four time points following intravenous administration of [11C]D617 (50 MBq) without (n=4) or with (n=4) pretreatment with the P-gp inhibitor tariquidar (15 mg·kg−1, intraperitoneally). Brain distribution was further assessed using consecutive PET scans (n=8) before and after pretreatment with tariquidar (15 mg·kg−1, intravenously), as well as metabolite analysis (n=4).Results: The precursor for the radiosynthesis of [11C]D617, 5-amino-2-(3,4-dimethoxy-phenyl)-2-isopropyl-pentanitrile (desmethyl D617), was synthesized in 41% overall yield. [11C]D617 was synthesized in 58%–77% decay-corrected yield with a radiochemical purity of ≥99%. The homogeneously distributed cerebral volume of distribution (VT) of [11C]D617 was 1.1, and this increased 2.4-fold after tariquidar pretreatment.Conclusion: VT of [11C]D617 was comparable to that of (R)-[11C]verapamil, but its increase after tariquidar pretreatment was substantially lower. Hence, (R)-[11C]verapamil and [11C]D617 do not show similar brain kinetics after inhibition of P-gp with tariquidar.

Simple preparation and purification of ethanol-free solutions of 3′-deoxy-3′-[18F]fluorothymidine by means of disposable solid-phase extraction cartridges

2011-12-15

Abstract: Introduction: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) shows great potential as a tracer for proliferative studies with PET. However, its regular application is often limited by low radiochemical yields and the use of a troublesome HPLC separation. Moreover, a high content of ethanol, at least one-fold higher than the European Pharmacopoeia and US Pharmacopoeia's established limit, is always present in the final product. The present study reports an optimization of the reaction conditions and a simple and straightforward purification step which affords a solution of [18F]FLT suitable for human use.Methods: Several conditions and materials were tested for both the nucleophilic substitution and purification step. The latter was achieved by means of a series of commercial solid-phase extraction cartridges. Very conveniently, the whole one-pot synthesis was carried out on commercial automated modules using basically the same setup employed for the synthesis of [18F]FDG.Results: Under routine conditions, radiochemical yields of 37% [decay-corrected to start of synthesis (SOS)] were achieved in ca. 39 min from SOS, with radiochemical purities >98% (usually >99%). The negligible radiolysis observed could be easily suppressed by adding 0.5% of EtOH. Typical unlabelled chemical impurities detected were thymidine (0.15 ppm), thymine (0.28 ppm) and stavudine (0.05 ppm).Conclusions: A reliable, simple and efficient preparation of [18F]FLT has been developed, able to afford an ethanol-free solution of the tracer with no need for any HPLC purification. Because of its similarity to the [18F]FDG synthesis, the method can be readily implemented on basically all the commercial modules developed for this common radiotracer.

An automated module for the separation and purification of cyclotron-produced 99mTcO4−

2012-01-09

Abstract: Introduction: The shortage of reactor-produced molybdenum-99 (99Mo, t½=66 h) has renewed interest in alternative production methods of its daughter isotope, technetium-99m (99mTc, t½=6.02 h). While adsorption chromatography serves as a mechanism for selective elution of sodium pertechnetate from technetium generators, this method of purification is not sufficient for many alternative production methods. Several ion-separation/solid phase extraction chromatography methods are known, yet none have been demonstrated on cyclotron-produced [99mTc]TcO4−. Herein we describe the design, manufacture and optimization of a remotely operated module for the purification of sodium pertechnetate from a bulk solution of molybdate.Methods: The automated purification module was designed to separate [99mTc]TcO4− using either Dowex 1x8 or an Aqueous Biphasic Extraction Chromatography (ABEC) resin. 100Mo composite targets were irradiated with 18.5 MeV protons for 10 μA·h using an ASCI TR19 cyclotron. Once purified, the radiopharmaceutical quality of 99mTcO4− isolated from each process (Dowex and/or ABEC) was established by assaying for molybdate breakthrough, alumina levels and, in the case of the Dowex approach, residual organics.Results: The separation processes are efficient (75% for Dowex, 90% for ABEC) and complete in less than 30 min. Overall, up to 2.1 GBq of 99mTc was produced using the 100Mo(p,2n)99mTc transformation, processed using the separation module and subjected to a detailed chemical and radionuclidic analysis. Due to its expense and limited availability, 100MoO42− was recovered in >90% yield using a precipitation/filtration/lyophilization approach.Conclusions: Na[99mTc]TcO4 was produced using a medical cyclotron, recovered using an automated purification module and found to exceed all established quality control parameters.

68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers

Morten Persson, Jacob Madsen, Søren Østergaard, Michael Ploug, Andreas Kjaer — 2011-12-15

Abstract: Introduction: The urokinase-type plasminogen activator receptor (uPAR) is a well-established biomarker for tumor aggressiveness and metastatic potential. DOTA-AE105 and DOTA-AE105-NH2 labeled with 64Cu have previously been demonstrated to be able to noninvasively monitor uPAR expression using positron emission tomography (PET) in human cancer xenograft mice models. Here we introduce 68Ga-DOTA-AE105-NH2 and 68Ga-NODAGA-AE105-NH2 and evaluate their imaging properties using small-animal PET.Methods: Synthesis of DOTA-AE105-NH2 and NODAGA-AE105-NH2 was based on solid-phase peptide synthesis protocols using the Fmoc strategy. 68GaCl3 was eluted from a 68Ge/68Ga generator. The eluate was either concentrated on a cation-exchange column or fractionated and used directly for labeling. For in vitro characterization of both tracers, partition coefficient, buffer and plasma stability, uPAR binding affinity and cell uptake were determined. To characterize the in vivo properties, dynamic microPET imaging was carried out in nude mice bearing human glioma U87MG tumor xenograft.Results: In vitro experiments revealed uPAR binding affinities in the lower nM range for both conjugated peptides and identical to AE105. Labeling of DOTA-AE105-NH2 and NODAGA-AE105-NH2 with 68Ga was done at 95°C and room temperature, respectively. The highest radiochemical yield and purity were obtained using fractionated elution, whereas a negative effect of acetone on labeling efficiency for NODAGA-AE105-NH2 was observed. Good stability in phosphate-buffered saline and mouse plasma was observed. High cell uptake was found for both tracers in U87MG tumor cells. Dynamic microPET imaging demonstrated good tumor-to-background ratio for both tracers. Tumor uptake was 2.1% ID/g and 1.3% ID/g 30 min postinjection and 2.0% ID/g and 1.1% ID/g 60 min postinjection for 68Ga-NODAGA-AE105-NH2 and 68Ga-DOTA-AE105-NH2, respectively. A significantly higher tumor-to-muscle ratio (P<.05) was found for 68Ga-NODAGA-AE105-NH2 60 min postinjection.Conclusions: The use of 68Ga-DOTA-AE105-NH2 and 68Ga-NODAGA-AE105-NH2 as the first gallium-68 labeled uPAR radiotracers for noninvasive PET imaging is reported, which combine versatility with good imaging properties. These new tracers thus constitute an interesting alternative to the 64Cu-labeled version (64Cu-DOTA-AE105 and 64Cu-DOTA-AE105-NH2) for detecting uPAR expression in tumor tissue. In our hands, the fractionated elution approach was superior for labeling of peptides, and 68Ga-NODAGA-AE105-NH2 is the favored tracer as it provides the highest tumor-to-background ratio.

Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

2011-12-15

Abstract: Introduction: The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [18F]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics.Methods: Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [18F]DPA-714 (245±45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time–activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values.Results: The effective dose estimated from biodistribution in mice was 17.2 μSv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [18F]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5–30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys.Conclusions: This initial study in humans shows that [18F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [18F]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations.

Synthesis, radiolabeling, biodistribution and fluorescent imaging of histidine-coupled hematoporphyrin

Yupeng Liu, Bo Shen, Fei Liu, Bin Zhang, Taiwei Chu, Jing Bai, Shanglian Bao — 2012-01-09

Abstract: Introduction: Hematoporphyrin (Hp) and hematoporphyrin derivatives (HpDs) have been widely used as photosensitizers in photodynamic therapy (PDT). Radiolabeling of HpDs is helpful for preclinical and clinical studies of PDT.Methods: The histidine-coupled hematoporphyrin (His-Hp) was synthesized and radiolabeled with [99mTc(CO)3(H2O)3]+. Biodistribution of the radioligand and fluorescent imaging of His-Hp in mice bearing S180 tumor were investigated.Results: [99mTc(CO)3]+-labeled His-Hp was electrically neutral, hydrophilic and stable. The biodistribution of the radioligand in S180 tumor-bearing mice was similar with that of nonlabeled HpD in the literature. The uptake of His-Hp in tumors and livers was confirmed by fluorescent imaging.Conclusions: The complex [99mTc(CO)3]+–His-Hp might be suitable for in vivo dose evaluation of HpD in PDT.

Evaluation of an automated double-synthesis module: efficiency and reliability of subsequent radiosyntheses of FHBG and FLT

2011-12-15

Abstract: We optimized the synthesis methods for 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) and 9-(4-[18F]fluoro-3-[hydroxymethyl]butyl)guanine) ([18F]FHBG) and automated them on an Explora General Nucleophilic double-synthesis module. Furthermore, the synthesis efficiency and reliability and the formation of cross-contaminations of the products when preparing two consecutive batches were evaluated. Whereas the preinstalled FLT synthesis conditions required substantial modification in reaction and neutralization conditions to achieve radiochemical yields of up to 60% within 70±10 min including high-performance liquid chromatography purification, the synthesis of FHBG had to be implemented to the module to obtain competitive radiochemical yields of up to 40% in an overall synthesis time of 60±10 min. The radiochemical purities obtained were ≥99% and ≥96% for the synthesis of [18F]FLT and [18F]FHBG, respectively. No significant changes in yield or purity could be observed between both batch productions. We found that the yields and purities also did not change when performing FLT after FHBG syntheses and vice versa. Hence, we developed a synthesis setup that offers the opportunity to perform two subsequent syntheses of either [18F]FLT, [18F]FHBG or [18F]FLT after [18F]FHBG without decrease in radiochemical yields and purities. Also, no cross-contaminations were observed, which can be attributed to the use of separate product delivery tubes, purification columns and an automated intermediate cleaning program. These results open up the possibility of producing consecutively either two equal 18F-fluorinated tracers or two different ones in high yields on the same synthesis module.

Synthesis and preliminary evaluation of [18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor

2012-01-09

Abstract: Introduction: The cannabinoid receptor type 2 (CB2) is an important target for development of drugs and imaging agents for diseases, such as neuroinflammation, neurodegeneration and cancer. Recently, we reported synthesis and results of in vitro receptor binding of a focused library of fluorinated 2-oxoquinoline derivatives as CB2 receptor ligands. Some of the compounds demonstrated to be good CB2-specific ligands with Ki values in the nanomolar to subnanomolar concentrations; therefore, we pursued the development of their 18F-labeled analogues that should be useful for positron emission tomography (PET) imaging of CB2 receptor expression. Here, we report the radiosynthesis of two 18F-labeled 2-oxoquinoline derivatives and the preliminary in vitro and ex vivo evaluation of one compound as a CB2-specific radioligand.Methods: 4-[18F]fluorobenzyl amine [18F]-3 was prepared by radiofluorination of 4-cyano-N,N,N-trimethylanilinium triflate salt followed by reduction with LiAlH4 and then coupled with acid chlorides 11 and 12 to afford [18F]-13 and [18F]-14. In vitro CB2 receptor binding assay was performed using U87 cells transduced with CB2 and CB1 receptor. Ex vivo autoradiography was performed with [18F]-14 on spleen and on CB2- and CB1-expressing and wild-type U87 subcutaneous tumors grown in mice.Results: The radiochemical yields of [18F]-13 and [18F]-14 were 10%–15.0% with an average of 12% (n=10); radiochemical purity was >99% with specific activity 1200 mCi/μmol. The dissociation constant Kd for [18F]-14 was 3.4 nM. Ex vivo autoradiography showed accumulation of [18F]-14 in the CB2-expressing tumor.Conclusion: Two new [18F]-labeled CB2 ligands have been synthesized. Compound [18F]-14 appears to be a potential PET imaging agent for the assessment of CB2 receptor expression; however, poor solubility restrain its use in vivo.

2012-05-01

Nuclear Medicine and Biology

Editorial Board

Synthesis of oncological [11C]radiopharmaceuticals for clinical PET

Bombesin analogues for gastrin-releasing peptide receptor imaging

Combined-modality radioimmunotherapy: synergistic effect of paclitaxel and additive effect of bevacizumab

Preclinical studies of potential amyloid binding PET/SPECT ligands in Alzheimer's disease

An allogenic site-specific rat model of bone metastases for nuclear medicine and experimental oncology

Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions

Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with 111In using a maleimido derivative of NODAGA

Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil

Simple preparation and purification of ethanol-free solutions of 3′-deoxy-3′-[18F]fluorothymidine by means of disposable solid-phase extraction cartridges

An automated module for the separation and purification of cyclotron-produced 99mTcO4−

68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers

Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

Synthesis, radiolabeling, biodistribution and fluorescent imaging of histidine-coupled hematoporphyrin

Evaluation of an automated double-synthesis module: efficiency and reliability of subsequent radiosyntheses of FHBG and FLT

Synthesis and preliminary evaluation of [18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor

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