Positron-emitting Radionuclides Research Articles

Pd0-mediated rapid cross-coupling reactions, the rapid C-[11C]methylations, revolutionarily advancing the syntheses of short-lived PET molecular probes.

Positron emission tomography is a noninvasive method for monitoring drug (or diagnostic) behavior and its localization on the target molecules in the living systems, including the human body, using a short-lived positron-emitting radionuclide. New methodologies for introducing representative short-lived radionuclides, (11)C and (18)F, into the carbon frameworks of biologically active organic compounds have been established by developing rapid C-[(11)C]methylations and C-[(18)F]fluoromethylations using rapid Pd(0)-mediated cross-coupling reactions between [(11)C]methyl iodide (sp(3)-hybridized carbon) and an excess amount of organotributylstannane or organoboronic acid ester having sp(2) (phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp(3) (benzyl and cinnamyl)-hybridized carbons; and [(18)F]fluoromethyl halide (iodide or bromide) and an organoboronic acid ester, respectively. These rapid reactions provide a firm foundation for an efficient and general synthesis of short-lived (11)C- or (18)F-labeled PET molecular probes to promote in vivo molecular imaging studies.

Phosphinic Acid Functionalized Polyazacycloalkane Chelators for Radiodiagnostics and Radiotherapeutics: Unique Characteristics and Applications

Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron. Hence, interest in optimized bifunctional chelators for the elaboration of (68) Ga-labeled bioconjugates has been rekindled as well, resulting in the development of improved triazacyclononane-triphosphinate (TRAP) ligand structures. The most remarkable features of these ligands are unparalleled selectivity for Ga(III) , rapid Ga(III) complexation kinetics, extraordinarily high thermodynamic stability, and kinetic inertness of the respective Ga(III) chelates. As a result, TRAP chelators exhibit very favorable (68) Ga-labeling properties. Based on the scaffolds NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) and TRAP-Pr, tailored for convenient preparation of (68) Ga-labeled monomeric and multimeric bioconjugates, a variety of novel (68) Ga radiopharmaceuticals have been synthesized. These include bisphosphonates, somatostatin receptor ligands, prostate-specific membrane antigen (PSMA)-targeting peptides, and cyclic RGD pentapeptides, for in vivo PET imaging of bone, neuroendocrine tumors, prostate cancer, and integrin expression, respectively. Furthermore, TRAP-based (68) Ga-labeled gadolinium(III) complexes have been proposed as bimodal probes for PET/MRI, and a cyclen-based analogue of TRAP-Pr has been suggested for the elaboration of targeted radiotherapeutics comprising radiolanthanide ions. Thus, polyazacycloalkane-based polyphosphinic acid chelators are a powerful toolbox for pharmaceutical research, particularly for the development of (68) Ga radiopharmaceuticals.

An analytic reconstruction method for PET based on cubic splines

PET imaging is an important nuclear medicine modality that measures in vivo distribution of imaging agents labeled with positron-emitting radionuclides. Image reconstruction is an essential component in tomographic medical imaging. In this study, we present the mathematical formulation and an improved numerical implementation of an analytic, 2D, reconstruction method called SRT, Spline Reconstruction Technique. This technique is based on the numerical evaluation of the Hilbert transform of the sinogram via an approximation in terms of 'custom made' cubic splines. It also imposes sinogram thresholding which restricts reconstruction only within object pixels. Furthermore, by utilizing certain symmetries it achieves a reconstruction time similar to that of FBP. We have implemented SRT in the software library called STIR and have evaluated this method using simulated PET data. We present reconstructed images from several phantoms. Sinograms have been generated at various Poison noise levels and 20 realizations of noise have been created at each level. In addition to visual comparisons of the reconstructed images, the contrast has been determined as a function of noise level. Further analysis includes the creation of line profiles when necessary, to determine resolution. Numerical simulations suggest that the SRT algorithm produces fast and accurate reconstructions at realistic noise levels. The contrast is over 95% in all phantoms examined and is independent of noise level.

Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

Self-Illuminating 64Cu-Doped CdSe/ZnS Nanocrystals for in Vivo Tumor Imaging

Construction of self-illuminating semiconducting nanocrystals, also called quantum dots (QDs), has attracted much attention recently due to their potential as highly sensitive optical probes for biological imaging applications. Here we prepared a self-illuminating QD system by doping positron-emitting radionuclide 64Cu into CdSe/ZnS core/shell QDs via a cation-exchange reaction. The 64Cu-doped CdSe/ZnS QDs exhibit efficient Cerenkov resonance energy transfer (CRET). The signal of 64Cu can accurately reflect the biodistribution of the QDs during circulation with no dissociation of 64Cu from the nanoparticles. We also explored this system for in vivo tumor imaging. This nanoprobe showed high tumor-targeting ability in a U87MG glioblastoma xenograft model (12.7% ID/g at 17 h time point) and feasibility for in vivo luminescence imaging of tumor in the absence of excitation light. The availability of these self-illuminating integrated QDs provides an accurate and convenient tool for in vivo tumor imaging and detection.

Depicting Medullary Thyroid Cancer Recurrence: The Past and the Future of Nuclear Medicine Imaging

Context:Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and medically challenging malignancy. Even if the extent of initial surgery is deemed adequate, the recurrence rate remains high, up to 50% in most series. Measurement of serum calcitonin is important in the follow-up of patients with MTC, and reliably reflects the existence of the disease.Evidence Acquisition:There is no single sensitive diagnostic imaging method to reveal all MTC recurrences or metastases. Conventional morphologic imaging methods (U/S, CT, and MRI) and several methods of nuclear medicine have been used for this purpose with variable accuracy.Results:The main role of nuclear medicine imaging is the detection of residual or recurrent tumor in the postoperative follow-up. In this review we present the radiopharmaceuticals used in the diagnosis of MTC recurrence, and comparison among them.Conclusions:The most used radiopharmaceuticals labelled with γ emitters are: Metaiodobenzylguanidine (MIBG), labelled with 131I or 123I, 111In-pentetreotide (Octreoscan), 99mTc-pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA), and 99mTc-EDDA/HYNIC-Tyr3-Octreotide ( Tektrotyd). The radiopharmaceuticals labelled with a positron-emitting radionuclide (β+), suitable for positron emission tomography (PET) imaging are: 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodihydroxyphenylalanine (18F-DOPA), and 68Ga-labelled somatostatin analogues (68Ga-DOTATATE or DOTATOC).

Engineered antibodies for molecular imaging of cancer

Antibody technology has transformed drug development, providing robust approaches to producing highly targeted and active therapeutics that can routinely be advanced through clinical evaluation and registration. In parallel, there is an emerging need to access similarly targeted agents for diagnostic purposes, including non-invasive imaging in preclinical models and patients. Antibody engineering enables modification of key properties (immunogenicity, valency, biological inertness, pharmacokinetics, clearance route, site-specific conjugation) in order to produce targeting agents optimized for molecular imaging. Expanded availability of positron-emitting radionuclides has led to a resurgence of interest and applications of immunoPET (immuno-positron emission tomography). Molecular imaging using engineered antibodies and fragments provides a general approach for assessing cell surface phenotype in vivo and stands to play an increasingly important role in cancer diagnosis, treatment selection, and monitoring of molecularly targeted therapeutics.

Pediatric radiation dosimetry for positron‐emitting radionuclides using anthropomorphic phantoms

Positron emission tomography (PET) plays an important role in the diagnosis, staging, treatment, and surveillance of clinically localized diseases. Combined PET/CT imaging exhibits significantly higher sensitivity, specificity, and accuracy than conventional imaging when it comes to detecting malignant tumors in children. However, the radiation dose from positron-emitting radionuclide to the pediatric population is a matter of concern since children are at a particularly high risk when exposed to ionizing radiation. The authors evaluate the absorbed fractions and specific absorbed fractions (SAFs) of monoenergy photons/electrons as well as S-values of 9 positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124) in 48 source regions for 10 anthropomorphic pediatric hybrid models, including the reference newborn, 1-, 5-, 10-, and 15-yr-old male and female models, using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code. The self-absorbed SAFs and S-values for most organs were inversely related to the age and body weight, whereas the cross-dose terms presented less correlation with body weight. For most source/target organ pairs, Rb-82 and Y-86 produce the highest self-absorbed and cross-absorbed S-values, respectively, while Cu-64 produces the lowest S-values because of the low-energy and high-frequency of electron emissions. Most of the total self-absorbed S-values are contributed from nonpenetrating particles (electrons and positrons), which have a linear relationship with body weight. The dependence of self-absorbed S-values of the two annihilation photons varies to the reciprocal of 0.76 power of the mass, whereas the self-absorbed S-values of positrons vary according to the reciprocal mass. The produced S-values for common positron-emitting radionuclides can be exploited for the assessment of radiation dose delivered to the pediatric population from various PET radiotracers used in clinical and research settings. The mass scaling method for positron-emitters can be used to derive patient-specific S-values from data of reference phantoms.

Age-Dependent Small-Animal Internal Radiation Dosimetry

Rats at various ages were observed to present with different radiosensitivity and bioavailability for radiotracers commonly used in preclinical research. We evaluated the effect of age-induced changes in body weight on radiation dose calculations. A series of rat models at different age periods were constructed based on the realistic four-dimensional digital rat whole-body (ROBY) computational model. Particle transport was simulated using the MCNPX Monte Carlo code. Absorbed fractions (AFs) and specific absorbed fraction (SAFs) of monoenergetic photons/electrons and S values of eight positron-emitting radionuclides were calculated. The SAFs and S values for most source-target pairs were inversely correlated with body weight. Differences between F-18 S values for most source-target pairs were between -1.5% and -2%/10 g difference in body weight for different computational models. For specific radiotracers, the radiation dose to organs presents a negative correlation with rat body weight. The SAFs for monoenergetic photons/electrons and S values for common positron-emitting radionuclides can be exploited in the assessment of radiation dose delivered to rats at different ages and weights. The absorbed dose to organs is significantly higher in the low-weight young rat model than in the adult model, which would result in steep secondary effects and might be a noteworthy issue in laboratory animal internal dosimetry.

Effect of emaciation and obesity on small-animal internal radiation dosimetry for positron-emitting radionuclides

Rats are widely used in biomedical research involving molecular imaging and therefore the radiation dose to animals has become a concern. The weight of laboratory animals might change through emaciation or obesity as a result of their use in various research experiments including those investigating different diet types. In this work, we evaluated the effects of changes in body weight induced by emaciation and obesity on the internal radiation dose from common positron-emitting radionuclides. A systematic literature review was performed to determine normal anatomical parameters for adult rats and evaluate how organs change with variations in total body weight. The ROBY rat anatomical model was then modified to produce a normal adult rat, and mildly, moderately and severely emaciated and obese rats. Monte Carlo simulations were performed using MCNPX to estimate absorbed fractions, specific absorbed fractions (SAFs) and S-values for these models using different positron-emitting radionuclides. The results obtained for the different models were compared to corresponding estimates from the normal rat model. The SAFs and S-values for most source-target pairs between the various anatomical models were not significantly different, except where the intestine and the total body were considered as source regions. For the intestine, irradiating other organs in the obese model, the SAFs in organs in the anterior region of the splanchnocoele (e.g. kidney, liver and stomach) increased slightly, whereas the SAFs in organs in the posterior region of the splanchnocoele (e.g. bladder and testes) decreased owing to the increase in the distance separating the intestine and posterior abdominal organs because of the rat epididymal fat pad. For the total body, irradiating other organs, the SAFs and S-values were inversely related to body weight. The effect of obesity on internal radiation dose is insignificant in most conditions for common positron-emitting radionuclides. Emaciation increases the cross-absorbed dose to organs from surrounding tissues, which might be a notable issue in laboratory animal internal dosimetry.

Production and Purification of Metal Radionuclides for PET Imaging of Disease

The applications of radiopharmaceuticals labeled with positron-emitting metal radionuclides for positron emission tomography (PET) imaging have been increasing steadily over the past 20 years. The methods used for production and purification of the radionuclides are important for producing high specific activity agents, as this is critical for imaging low capacity receptors that are upregulated in diseased tissues. In this review we outline state-of-the-art methodologies for producing four widely used metal radionuclides (Cu-64, Ga-68, Y-86, and Zr-89) and the various purification schemes that are involved in preparing these radionuclides for their use in PET radiopharmaceuticals.

Influence of Nuclides and Chelators on Imaging Using Affibody Molecules: Comparative Evaluation of Recombinant Affibody Molecules Site-Specifically Labeled with 68Ga and 111In via Maleimido Derivatives of DOTA and NODAGA

Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use of the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity of HER2 imaging. The chemical nature of radionuclides and chelators influences the biodistribution of Affibody molecules, providing an opportunity to further increase the imaging contrast. The aim of the study was to compare maleimido derivatives of DOTA and NODAGA for site-specific labeling of a recombinant ZHER2:2395 HER2-binding Affibody molecule with (68)Ga. DOTA and NODAGA were site-specifically conjugated to the ZHER2:2395 Affibody molecule having a C-terminal cysteine and labeled with (68)Ga and (111)In. All labeled conjugates retained specificity to HER2 in vitro. Most of the cell-associated activity was membrane-bound with a minor difference in internalization rate. All variants demonstrated specific targeting of xenografts and a high tumor uptake. The xenografts were clearly visualized using all conjugates. The influence of chelator on the biodistribution and targeting properties was much less pronounced for (68)Ga than for (111)In. The tumor uptake of (68)Ga-NODAGA-ZHER2:2395 and (68)Ga-DOTA-ZHER2:2395 and tumor-to-blood ratios at 2 h p.i. did not differ significantly. However, the tumor-to-liver ratio was significantly higher for (68)Ga-NODAGA- ZHER2:2395 (8 ± 2 vs 5.0 ± 0.3) offering the advantage of better liver metastases visualization. In conclusion, influence of chelators on biodistribution of Affibody molecules depends on the radionuclides and reoptimization of labeling chemistry is required when a radionuclide label is changed.

SAT0256 Hybrid 18F-Fluoride Positron Emission Tomography and Magnetic Resonance Imaging (18F-F-Pet/MRI) of the Spine – A Pilot Study and Comparison of Signals in Patients with Axial Spondyloarthritis

BackgroundPET is a nuclear imaging technique that depicts functional processes within the body by detecting pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), introduced into the body...

Peptide receptor imaging in neuroendocrine tumors: comparison between diagnostic scintigraphy and post-therapy whole-body scan

Several different somatostatin analogs labeled with gamma or positron-emitting radionuclides exist for diagnostic imaging of neuroendocrine tumors (NETs). Differences between standard diagnostic scintigraphy (SDS) and post-therapy whole-body scan (PTWBS) at peptide receptor radionuclide therapy in lesion detection are known; such differences have been correlated with the varying degree of receptor subtype expression and the varying receptor affinity profile of the different ligands. The aim of this study is to investigate differences between SDS and PTWBS obtained using the same radiopharmaceutical. We retrospectively reviewed clinical records of 53 patients with a diagnosis of NET, who underwent both SDS and PTWBS using (111)In-Pentetreotide. We compared the number of lesions for each body region detected by SDS and PTWBS. In 14/53 patients (26.4%) discrepancies between SDS and PTWBS were found. PTWBS detected 68 additional lesions with respect to SDS that were distributed as follows: head and neck, 6; mediastinum, 1; liver, 10; abdomen/pelvis, 1; bone, 44; other localizations, 6. The number of lesions detected by SDS was significantly different from that revealed by PTWBS (Wilcoxon matched pairs test, P = 0.0313). The regions that contributed significantly to reach this difference were head and neck (McNemar test, P = 0.0412), liver (McNemar test, P = 0.0044), bone (McNemar test, P < 0.0001) and other localizations (McNemar test, P = 0.0412). PTWBS shows more lesions than SDS with a significant discrepancy. We suppose that administration of higher radiopharmaceutical activity, use of larger peptide amount and the different time interval between radiopharmaceutical administration and scan execution can determine a higher sensitivity of PTWBS.

Assessment of S Values in Stylized and Voxel-Based Rat Models for Positron-Emitting Radionuclides

Positron emission tomography (PET) is a powerful tool in small animal research, enabling noninvasive quantitative imaging of biochemical processes in living subjects. However, the dosimetric characteristics of small animal PET imaging are usually overlooked, although the radiation dose may be significant. The variations of anatomical characteristics between the various computational models may result in differences in the dosimetric outcome. We used five different anatomical rat models (two stylized and three voxel based) to compare calculated absorbed fractions and S values for eight positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Y-86, and I-124) commonly used to label various probes for small animal PET imaging. The MCNPX radiation transport code was used for radiation dose calculations. For most source/target organ pairs, O-15 and Ga-68 produce the highest self-absorbed S values because of the high-energy and high-frequency of positron emissions, while Y-86 produces the highest cross-absorbed S values because of the high energy and high frequency of γ-rays emission. Anatomical models produced from different rat strains or modeling techniques exhibit different organ masses, volumes, and thus give rise to different S values and absorbed dose. The variations of absorbed fractions between models of the same type are less than those between models with different types. The calculated S values depend strongly on organ mass, and as such, different models produce similar S values for organs of comparable masses. In most source organs presenting with high cumulated activity, the absorbed dose is less affected by model difference compared with other organs. The produced S values for common positron-emitting radionuclides can be exploited in the assessment of radiation dose to rats from different radiotracers used in small animal PET experiments. This work contributes to a better understanding of the influence of different computational models on small animal dosimetry.

Molecular Imaging-based Early-Phase and Exploratory Clinical Research

In vivo molecular imaging became a key technology for innovative drug development. Especially, positron emission tomography (PET) has been applied to patho-physiological science, pharmacodynamics/pharmacokinetics (PD/PK) studies, and drug delivery system (DDS) studies, and accelerated the paradigm shift not only from experimental animals to human subjects, but also from PK in blood circulation to PK in target tissues, even in human. Our RIKEN Centre for Molecular Imaging Science has been established to promote such innovative drug developmental studies with PET molecular imaging, as a center of excellence for development of molecular probes. The center is creating novel labeling methods on drug candidate molecules with positron-emitting radionuclides, and is providing the molecular probes suitable for targeting bio-functional molecules and cellular functions, which are useful for evaluation of drug efficacy and pharmacokinetics in human subjects. Animal PET studies with mice, rats, rabbits, marmosets, and macaque monkeys have also been promoted both under anesthetic condition and consciousness, which was a really difficult task but important for comparison with human PET studies. In this sense, mutual collaboration between the research consortia in basic PET field and in clinical PET molecular imaging such as Osaka City University Hospital would be of great value. Here, the concept, outline of our activities, and PK/PD studies with efficient application of molecular imaging is presented. In addition, the results of the first cassette-dose and micro-dose clinical trials approved by Pharmaceuticals and Medical Devices Agency (PMDA) (New Energy and Industrial Technology Development Organization (NEDO) project represented by Prof. Yuichi Sugiyama) are described.

Equilibrium and pre-equilibrium calculations of cross-sections of (p, xn) reactions on 89 Y, 90 Zr and 94 Mo targets used for the production of 89 Zr, 90 Nb and 94 Tc positron-emitting radionuclides

In this study, the pre-equilibrium and equilibrium calculations of cross-sections of 89Y(p, xn), 90Zr(p, xn) and 94Mo(p, xn) reactions, which were used for the production of 89Zr, 90Nb and 94Tc positron-emitting radioisotopes, have been investigated. Pre-equilibrium calculations have been performed at different proton incident energies by using the hybrid, geometry-dependent-hybrid and full exciton models. The Weisskopf–Ewing model is used for calculating the equilibrium effects at the same incident energies. The calculated results have been discussed and compared with the experimental results.

Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50-MV photon radiation therapy

BackgroundThe purpose of this work was to reveal the research interest value of positron emission tomography (PET) imaging in visualizing the induced tissue activity post high-energy photon radiation treatment. More specifically, the focus was on the possibility of retrieving data such as tissue composition and physical half-lives from dynamic PET acquisitions, as positron-emitting radionuclides such as 15O, 11C, and 13N are produced in vivo during radiation treatment with high-energy photons (>15 MeV). The type, amount, and distribution of induced positron-emitting radionuclides depend on the irradiated tissue cross section, the photon spectrum, and the possible perfusion-driven washout.MethodsA 62-year-old man diagnosed with prostate cancer was referred for palliative radiation treatment of the pelvis minor. A total dose of 8 Gy was given using high-energy photon beams (50 MV) with a racetrack microtron, and 7 min after the end of irradiation, the patient was positioned in a PET/computed tomography (CT) camera, and a list-mode acquisition was performed for 30 min. Two volumes of interests (VOIs) were positioned on the dynamic PET/CT images, one in the urinary bladder and the other in the subcutaneous fat. Analysis of the measured relative count rate was performed in order to compute the tissue compositions and physical half-lives in the two regions.ResultsDynamic analysis from the two VOIs showed that the decay constants of activated oxygen and carbon could be deduced. Calculation of tissue composition from analyzing the VOI containing subcutaneous fat only moderately agreed with that of the tabulated International Commission on Radiation Units & Measurements (ICRU) data of the adipose tissue. However, the same analysis for the bladder showed a good agreement with that of the tabulated ICRU data.ConclusionsPET can be used in visualizing the induced activity post high-energy photon radiation treatment. Despite the very low count rate in this specific application, wherein 7 min after treatment was about 5% of that of a standard 18F-FDG PET scan, the distribution of activated tissue elements (15O and 11C) could be calculated from the dynamic PET data. One possible future application of this method could possibly be to measure and determine the tumor tissue composition in order to identify any hypoxic or necrotic region, which is information that can be used in the ongoing therapy planning process.Trial registrationThe official name of the trial committee of this study is ‘Regionala etikprövningsnämnden i Stockholm’ (FE 289, Stockholm, SE-17177, Sweden). The unique identifying number is 2011/1789-31/2.

Pd0-mediated rapid coupling of methyl iodide with excess amounts of benzyl- and cinnamylboronic acid esters: efficient method for incorporation of positron-emitting 11C radionuclide into organic frameworks by coupling between two sp3-hybridized carbons

Pd0-mediated rapid cross coupling between sp3-hybridized carbons of CH3I and benzyl- or cinnamylboronic acid esters using [Pd{P(tert-C4H9)3}2]/CsF in DMF/H2O gave the corresponding methylated compounds in high yield. The utility was well demonstrated for the synthesis of short-lived PET tracer, N-(4-[11C]ethylphenyl)propionamide, in 90 ± 1% radio-HPLC analytical yield and 49 ± 3% radiochemical yield.

Monte Carlo-based evaluation of S-values in mouse models for positron-emitting radionuclides

In addition to being a powerful clinical tool, Positron emission tomography (PET) is also used in small laboratory animal research to visualize and track certain molecular processes associated with diseases such as cancer, heart disease and neurological disorders in living small animal models of disease. However, dosimetric characteristics in small animal PET imaging are usually overlooked, though the radiation dose may not be negligible. In this work, we constructed 17 mouse models of different body mass and size based on the realistic four-dimensional MOBY mouse model. Particle (photons, electrons and positrons) transport using the Monte Carlo method was performed to calculate the absorbed fractions and S-values for eight positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Y-86 and I-124). Among these radionuclides, O-15 emits positrons with high energy and frequency and produces the highest self-absorbed S-values in each organ, while Y-86 emits γ-rays with high energy and frequency which results in the highest cross-absorbed S-values for non-neighbouring organs. Differences between S-values for self-irradiated organs were between 2% and 3%/g difference in body weight for most organs. For organs irradiating other organs outside the splanchnocoele (i.e. brain, testis and bladder), differences between S-values were lower than 1%/g. These appealing results can be used to assess variations in small animal dosimetry as a function of total-body mass. The generated database of S-values for various radionuclides can be used in the assessment of radiation dose to mice from different radiotracers in small animal PET experiments, thus offering quantitative figures for comparative dosimetry research in small animal models.