Application Of Positron Emission Tomography Research Articles

Experimental validation of improved 3D SBP positioning algorithm in PET applications using UW Phase II Board

Continuous scintillator-based detectors have been considered as a competitive and cheaper approach than highly pixelated discrete crystal positron emission tomography (PET) detectors, despite the need for algorithms to estimate 3D gamma interaction position. In this work, we report on the implementation of a positioning algorithm to estimate the 3D interaction position in a continuous crystal PET detector using a Field Programmable Gate Array (FPGA). The evaluated method is the Statistics-Based Processing (SBP) technique that requires light response function and event position characterization. An algorithm has been implemented using the Verilog language and evaluated using a data acquisition board that contains an Altera Stratix III FPGA. The 3D SBP algorithm was previously successfully implemented on a Stratix II FPGA using simulated data and a different module design. In this work, improvements were made to the FPGA coding of the 3D positioning algorithm, reducing the total memory usage to around 34%. Further the algorithm was evaluated using experimental data from a continuous miniature crystal element (cMiCE) detector module. Using our new implementation, average FWHM (Full Width at Half Maximum) for the whole block is 1.71±0.01mm, 1.70±0.01mm and 1.632±0.005mm for x, y and z directions, respectively. Using a pipelined architecture, the FPGA is able to process 245,000 events per second for interactions inside of the central area of the detector that represents 64% of the total block area. The weighted average of the event rate by regional area (corner, border and central regions) is about 198,000 events per second. This event rate is greater than the maximum expected coincidence rate for any given detector module in future PET systems using the cMiCE detector design.

Bismuth germanate coupled to near ultraviolet silicon photomultipliers for time-of-flight PET

Bismuth germanate (BGO) was a very attractive scintillator in early-generation positron emission tomography (PET) scanners. However, the major disadvantages of BGO are lower light yield and longer rise and decay time compared to currently popular scintillators such as LSO and LYSO. This results in poorer coincidence timing resolution and it has generally been assumed that BGO is not a suitable scintillator for time-of-flight (TOF) PET applications. However, when a 511 keV photon interacts in a scintillator, a number of Cerenkov photons are produced promptly by energetic electrons released by photoelectric or Compton interactions. If these prompt photons can be captured, they could provide a better timing trigger for PET. Since BGO has a high refractive index (increasing the Cerenkov light yield) and excellent optical transparency down to 320 nm (Cerenkov light yield is higher at shorter wavelengths), we hypothesized that the coincidence timing resolution of BGO can be significantly improved by efficient detection of the Cerenkov photons. However, since the number of Cerenkov photons is far less than the number of scintillation photons, and they are more abundant in the UV and blue part of the spectrum, photosensors need to have high UV/blue sensitivity, fast temporal response, and very low noise in order to trigger on the faint Cerenkov signal. In this respect, NUV-HD silicon photomultipliers (SiPMs) (FBK, Trento, Italy) are an excellent fit for our approach. In this study, coincidence events were measured using BGO crystals coupled with NUV-HD SiPMs. The existence and influence of Cerenkov photons on the timing measurements were studied using different configurations to exploit the directionality of the Cerenkov emissions. Coincidence resolving time values (FWHM) of ~270 ps from 2 × 3 × 2 mm3 BGO crystals and ~560 ps from 3 × 3 × 20 mm3 BGO crystals were obtained. To our knowledge, these are the best coincidence resolving time values reported for BGO to date. With these values, BGO can be considered as a relevant scintillator for TOF PET scanners, especially if photodetectors with even better near UV/blue response can be developed to further improve the efficiency of Cerenkov light detection.

Geoscientific process monitoring with positron emission tomography (GeoPET)

Abstract. Transport processes in geomaterials can be observed with input–output experiments, which yield no direct information on the impact of heterogeneities, or they can be assessed by model simulations based on structural imaging using µ-CT. Positron emission tomography (PET) provides an alternative experimental observation method which directly and quantitatively yields the spatio-temporal distribution of tracer concentration. Process observation with PET benefits from its extremely high sensitivity together with a resolution that is acceptable in relation to standard drill core sizes. We strongly recommend applying high-resolution PET scanners in order to achieve a resolution on the order of 1 mm. We discuss the particularities of PET applications in geoscientific experiments (GeoPET), which essentially are due to high material density. Although PET is rather insensitive to matrix effects, mass attenuation and Compton scattering have to be corrected thoroughly in order to derive quantitative values. Examples of process monitoring of advection and diffusion processes with GeoPET illustrate the procedure and the experimental conditions, as well as the benefits and limits of the method.

Clinical applications of PET using C-11/F-18-choline in brain tumours: a systematic review

The purpose of this study is to conduct a systematic review of the published data about the current indications in clinical practice for the use of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 (11C) or Fluorine-18 (18F) choline tracer in brain tumours. A comprehensive literature search of PubMed until April 30, 2016 with the Mesh terms: ‘‘positron emission tomography’’, ‘‘choline’’, and ‘‘brain neoplasm’’ was first performed. On a second step, the references of the retrieved articles were also screened, adding any relevant publications about the subject. A total of 15 articles corresponding to 453 patients with brain lesions (mostly gliomas) were included for the analysis, successfully imaging brain tumours for the following indications: diagnosis and tumour characterisation; biopsy guide; treatment planning; differential diagnosis of recurrence or radiation necrosis; and therapy response assessment and prognosis. In addition, other brain lesions have been imaged by PET choline, such as meningiomas and metastasis. PET or PET/CT with radiolabelled choline must be considered as an emerging procedure for the evaluation of brain tumours. Since choline has a low physiological uptake, it provides precise images with a very good tumour-to-background ratio, especially in lesions with disruption of the blood–brain barrier. Even though the small population and heterogeneity of analyzed studies precluded performing a meta-analysis, the exposed results in this review support the use of choline in the aforementioned indications based on its availability, but larger studies are needed to better validate its use.

Calculation of the (p,n) Reaction Cross Section of Radionuclides Used for PET Applications

Radioisotopes release their energy by emitting gamma rays, which can be detected with modern equipment. There are many radionuclide substances which are suitable for use in diagnostics. A small part of them is used as the radiation source for therapeutic purposes. Radioisotopes used in medical field are produced in accelerators or using nuclear reactors. In the production of artificial radioisotopes, the high energy particles of the incoming beam collide with the nuclei. Cross section of the reaction, is used to characterize the reduction of the incoming beam [1]. Cross-section plays an important role in the production of radioisotopes. In recent years positron emission tomography (PET) imaging technique is widely used for diagnostic purposes in nuclear medicine in our country. This imaging technique is used for the early diagnosis of cancer diseases and is used in the heart-related studies. F, C, N, O positron-emitting radionuclides are produced for PET applications [2]. Nowadays however, other short-lived radionuclides such as Cu, Ga, Br are under study. Cu radioisotope is used in the PET imaging. Ga is used in the PET imaging of biological processes in target tissues. Br is used in DNA studies, in the studies of the nerves of the heart and in digital imaging. After a radioactive decay process of the radionuclide, the resulting nucleus becomes stable. Meanwhile, a proton is transformed into two new particles, a positively charged positron and a neutron. Positron is thrown out from the nucleus. The advancing positron, after a short distance, collides with electrons of another atom. As a result, the energy of the destroyed mass is transformed into the energy of two gamma quanta of 511 keV, which propagate in opposite directions. Radiation therapy is a form of cancer treatment that uses radiation to destroy malignant cells. For this

Preliminary Research of CZT Based PET System Development in KAERI

Background: For positron emission tomography (PET) application, cadmium zinc telluride (CZT) has been investigated by several institutes to replace detectors from a conventional system using photomultipliers or Silicon-photomultipliers (SiPMs). The spatial and energy resolution in using CZT can be superior to current scintillator-based state-of-the-art PET detectors. CZT has been under development for several years at the Korea Atomic Energy Research Institute (KAERI) to provide a high performance gamma ray detection, which needs a single crystallinity, a good uniformity, a high stopping power, and a wide band gap. Materials and Methods: Before applying our own grown CZT detectors in the prototype PET system, we investigated preliminary research with a developed discrete type data acquisition (DAQ) system for coincident events at 128 anode pixels and two common cathodes of two CZT detectors from Redlen. Each detector has a 19.4×19.4×6 mm3 volume size with a 2.2 mm anode pixel pitch. Discrete amplifiers consist of a preamplifier with a gain of 8 mV·fC-1 and noise of 55 equivalent noise charge (ENC), a CR-RC4 shaping amplifier with a 5 μs peak time, and an analog-to-digital converter (ADC) driver. The DAQ system has 65 mega-sample per second flash ADC, a self and external trigger, and a USB 3.0 interface. Results and Discussion: Characteristics such as the current-to-voltage curve, energy resolution, and electron mobility life-time products for CZT detectors are investigated. In addition, preliminary results of gamma ray imaging using 511 keV of a 22Na gamma ray source were obtained. Conclusion: In this study, the DAQ system with a CZT radiation sensor was successfully developed and a PET image was acquired by two sets of the developed DAQ system.

New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64: Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging.

Bifunctional chelators play an important role in developing metallic radionuclide-based radiopharmaceuticals. In this study, a new bifunctional ligand, p-SCN-PhPr-NE3TA, was synthesized and conjugated to a very late antigen-4 targeting peptidomimetic, LLP2A, for evaluating its application in (64)Cu-based positron emission tomography (PET) imaging. The new ligand exhibited strong selective coordination of Cu(II), leading to a robust Cu complex, even in the presence of 10-fold Fe(III). The LLP2A conjugate of p-SCN-PhPr-NE3TA was prepared and successfully labeled with (64)Cu under mild conditions. The conjugate (64)Cu-NE3TA-PEG4-LLP2A showed significantly higher specific activity, compared with (64)Cu-NOTA-PEG4-LLP2A, while maintaining comparable serum stability. Subsequent biodistribution studies and PET imaging in mice bearing B16F10 xenografts confirmed its favorable in vivo performance and high tumor uptake with low background, rendering p-SCN-PhPr-NE3TA a promising bifunctional chelator for (64)Cu-based radiopharmaceuticals.

Digital silicon photomultiplier readout of a new fast and bright scintillation crystal (Ce:GFAG)

A new Gadolinium Fine Aluminum Gallate (Ce:GFAG) scintillation crystal with both high energy resolution and fast timing properties has successfully been grown. Compared to Gd3Al2Ga3O12 (Ce:GAGG), this new inorganic scintillation crystal has a high luminosity similar to and a faster decay time. In this paper, we report on the timing and energy performance results of the new GFAG scintillation crystal read out with digital silicon photomultipliers (dSiPM) for positron emission tomography (PET) application. The best coincidence resolving time (FWHM) of polished 3×3×5mm3 crystals was 223±6ps for GFAG crystals compared to 396±28ps for GAGG crystals and 131±3ps for LYSO crystals respectively. An energy resolution (511keV peak of Na-22) of 10.9±0.2% was attained with GFAG coupled to dSiPM after correcting for saturation effect, compared to 9.5±0.3% for Ce:GAGG crystals and 11.9±0.4% for LYSO crystals respectively. It is expected that this new scintillator may be competitive in terms of overall properties such as energy resolution, timing resolution and growing (raw material) cost, compared to existing scintillators for positron emission tomography (PET).

A 32 mm × 32 mm × 22 mm monolithic LYSO:Ce detector with dual-sided digital photon counter readout for ultrahigh-performance TOF-PET and TOF-PET/MRI

New applications for positron emission tomography (PET) and combined PET/magnetic resonance imaging (MRI) are currently emerging, for example in the fields of neurological, breast, and pediatric imaging. Such applications require improved image quality, reduced dose, shorter scanning times, and more precise quantification. This can be achieved by means of dedicated scanners based on ultrahigh-performance detectors, which should provide excellent spatial resolution, precise depth-of-interaction (DOI) estimation, outstanding time-of-flight (TOF) capability, and high detection efficiency. Here, we introduce such an ultrahigh-performance TOF/DOI PET detector, based on a 32 mm × 32 mm × 22 mm monolithic LYSO:Ce crystal. The 32 mm × 32 mm front and back faces of the crystal are coupled to a digital photon counter (DPC) array, in so-called dual-sided readout (DSR) configuration. The fully digital detector offers a spatial resolution of ~1.1 mm full width at half maximum (FWHM)/~1.2 mm mean absolute error, together with a DOI resolution of ~2.4 mm FWHM, an energy resolution of 10.2% FWHM, and a coincidence resolving time of 147 ps FWHM. The time resolution closely approaches the best results (135 ps FWHM) obtained to date with small crystals made from the same material coupled to the same DPC arrays, illustrating the excellent correction for optical and electronic transit time spreads that can be achieved in monolithic scintillators using maximum-likelihood techniques for estimating the time of interaction. The performance barely degrades for events with missing data (up to 6 out of 32 DPC dies missing), permitting the use of almost all events registered under realistic acquisition conditions. Moreover, the calibration procedures and computational methods used for position and time estimation follow recently made improvements that make them fast and practical, opening up realistic perspectives for using DSR monolithic scintillator detectors in TOF-PET and TOF-PET/MRI systems.

Towards monolithic scintillator based TOF-PET systems: practical methods for detector calibration and operation

Gamma-ray detectors based on thick monolithic scintillator crystals can achieve spatial resolutions <2 mm full-width-at-half-maximum (FWHM) and coincidence resolving times (CRTs) better than 200 ps FWHM. Moreover, they provide high sensitivity and depth-of-interaction (DOI) information. While these are excellent characteristics for clinical time-of-flight (TOF) positron emission tomography (PET), the application of monolithic scintillators has so far been hampered by the lengthy and complex procedures needed for position- and time-of-interaction estimation. Here, the algorithms previously developed in our group are revised to make the calibration and operation of a large number of monolithic scintillator detectors in a TOF-PET system practical. In particular, the k-nearest neighbor (k-NN) classification method for x,y-position estimation is accelerated with an algorithm that quickly preselects only the most useful reference events, reducing the computation time for position estimation by a factor of ~200 compared to the previously published k-NN 1D method. Also, the procedures for estimating the DOI and time of interaction are revised to enable full detector calibration by means of fan-beam or flood irradiations only. Moreover, a new technique is presented to allow the use of events in which some of the photosensor pixel values and/or timestamps are missing (e.g. due to dead time), so as to further increase system sensitivity. The accelerated methods were tested on a monolithic scintillator detector specifically developed for clinical PET applications, consisting of a 32 mm × 32 mm × 22 mm LYSO : Ce crystal coupled to a digital photon counter (DPC) array. This resulted in a spatial resolution of 1.7 mm FWHM, an average DOI resolution of 3.7 mm FWHM, and a CRT of 214 ps. Moreover, the possibility of using events missing the information of up to 16 out of 64 photosensor pixels is shown. This results in only a small deterioration of the detector performance.

Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging.

The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using (64) CuATSM [copper (diacetyl-bis(N4-methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21(st) century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in "cold" and "hot" Cu(II) and Ga(III) derivatives for PET applications and (111) In(III) derivatives for SPECT (single-photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium-based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications.

Possibilities of positron emission tomography in the metastatic breast cancer diagnosis

An analysis of published data on the possibilities of the positron emission tomography method application in complex diagnostic and treatment activities in metastatic breast cancer was performed. The possibilities are described and the method characteristics according to series of studies, in particular with regard to the various localization metastases identification are given. It is noted that, compared with conventional imaging techniques, positron emission tomography is more sensitive and specific method of distant metastases diagnosis. The results of clinical studies on assessment of the method application possibilities in the detection of breast cancer metastases in lymph nodes, various organs and bone metastases are given. It has been shown that the introduction of sodium fluoride into practice allowed to use this agent as bone tissue biomarker, which can be used in positron emission tomography performing. The data that the simultaneous use of positron emission tomography with 18F-fluorodeoxyglucose and computed tomography has a high diagnostic value in relation to the breast cancer distant metastases detection are presented. The method possibilities for the various forms of primary invasive breast cancer identification, including invasive ductal and lobular cancer are considered. The prospects analysis for a further increase of opportunities for positron emission tomography application is performed, in particular, reports on the possibility of so-called hybrid scanning using positron emission tomography and magnetic resonance imaging are considered. It is highlighted that the most important aim of the method use in clinical practice in the prospect may be local-regional recurrence and distant metastasis monitoring after primary treatment for breast cancer.

Performance of FBK low-afterpulse NUV silicon photomultipliers for PET application

The improvement of the coincidence resolving time (CRT) is one of the key factors for the next generation of positron emission tomography (PET) scanners. Silicon photomultipliers (SiPMs) are strong candidates to substitute photo multipliers tubes because of their compactness, ruggedness and insensitivity to magnetic fields. In order to achieve the best CRT, the SiPM should have high PDE which can be obtained increasing the bias voltage. We recently improved the NUV SiPM technology, with the addition of a new substrate type that provides significantly lower afterpulsing probability (Low-AP). This enables to extend the maximum bias voltage and thus obtain higher PDE. Additionally, we implemented a lower electric field version (Low-F) to reduce the field-enhanced thermal generation components of the dark count rate. In this work we present results of energy and timing resolution for PET application, using LYSO scintillator crystals, and coupled with 3 × 3 mm2 NUV SiPMs of three types: non-Low-AP, Low-AP and Low-AP + Low-F. All the devices reach very similar energy resolutions, around 9.5 %, and close to the intrinsic limit of the LYSO. Concerning the timing resolution, we found that the Low-AP substrate achieves an improvement of the CRT of ≈ 30 ps, confirmed with the Low-F. Using 4 × 4 mm2 Low-AP SiPMs coupled to 3 × 3 × 5 mm3 and 3.8 × 3.8 × 22 mm3 LYSO crystals we obtained CRTs of 130 and 200 ps FWHM, respectively.

Frequency based gating: An alternative, conformal, approach to 4D PET data utilization.

Respiratory gating is a strategy for overcoming image degradation caused by patient motion in Positron Emission Tomography (PET) imaging. Traditional methods for sorting data, namely, phase-based gating or amplitude-based gating, come with an inherent trade-off between resolution improvements and added noise present in the subjugated data. If the goal of motion correction in PET is realigned from creating 4D images that attempt to mimic nongated images, towards ideal utilization of the information available, then new paths for data management emerge. In this work, the authors examine the application of a method in a new class of frequency based data subjugation algorithms, termed gating +. This strategy utilizes data driven information to locally adapt signal to its optimal segregation, thereby creating a new approach to 4D data utilization PET. 189 (18)F-fluorodeoxyglucose (FDG) PET scans were acquired at a single bed position centered on the thorax region. 4D gated image sets were reconstructed using data driven gating. The gating+ signal optimization algorithm, previously presented in small animal PET images and simulations, was used to segregate data in frequency space to generate optimized 4D images in the population-the first application and analysis of gating+ in human PET scans. The nongated, phase gated, and gating+ representations of the data were compared using FDG uptake analysis in the identified lesions and noise measurements from background regions. Optimized processing required less than 1 min per scan on a standard PC (plus standard reconstruction time), and yielded entire 4D optimized volumes plus motion maps. Optimized scans had noise characteristics similar to nongated images, yet also contained much of the resolution and motion information found in the gated images. The average SUVmax increase in the lesion sample between gated/nongated and gating+/nongated (±SD in population) was 35.8% ± 34.6% and 28.6% ± 27.9%, respectively. The average percent standard deviation (%SD ± SD in population) in liver volumes of interest (VOIs) across the sample for the nongated, gated, and gating+ scans was 6.7% ± 2.4%, 13.6% ± 3.3%, and 7.1% ± 2.5%, respectively. In all cases, the noise in the gating+ liver VOIs was closer to the nongated measurements than to the gated. The gating+ algorithm introduces the notion of conforming 4D data segregation to the local information and statistics that support it. By segregating data in frequency space, the authors are able to generate low noise motion information rich image sets, derived solely from selective use of raw data. Their work shows that the gating+ algorithm can be robustly applied in populations, and across varying qualities of motion and scans statistics, and be integrated as part of a fully automated motion correction workflow. Furthermore, the idea of smart signal utilization underpins a new concept of low risk or even risk-free motion correction application in PET.

Development of 89Zr-Ontuxizumab for in vivo TEM-1/endosialin PET applications.

PurposeThe complexity of sarcoma has led to the need for patient selection via in vivo biomarkers. Tumor endothelial marker-1 (TEM-1) is a cell surface marker expressed by the tumor microenvironment. Currently MORAb-004 (Ontuxizumab), an anti-TEM-1 humanized monoclonal antibody, is in sarcoma clinical trials. Development of positron emission tomography (PET) for in vivo TEM-1 expression may allow for stratification of patients, potentially enhancing clinical outcomes seen with Ontuxizumab.ResultsCharacterization of cell lines revealed clear differences in TEM-1 expression. One high expressing (RD-ES) and one low expressing (LUPI) cell line were xenografted, and mice were injected with 89Zr-Ontuxizumab. PET imaging post-injection revealed that TEM-1 was highly expressed and readily detectable in vivo only in RD-ES. In vivo biodistribution studies confirmed high radiopharmaceutical uptake in tumor relative to normal organs.Experimental DesignSarcoma cell lines were characterized for TEM-1 expression. Ontuxizumab was labeled with 89Zr and evaluated for immunoreactivity preservation. 89Zr-Ontuxizumab was injected into mice with high or null expressing TEM-1 xenografts. In vivo PET imaging experiments were performed.Conclusion89Zr-Ontuxizumab can be used in vivo to determine high versus low TEM-1 expression. Reliable PET imaging of TEM-1 in sarcoma patients may allow for identification of patients that will attain the greatest benefit from anti-TEM-1 therapy.

Trithiols and their arsenic compounds for potential use in diagnostic and therapeutic radiopharmaceuticals

IntroductionArsenic-72 (72As; 2.49MeV β+, 26h) and 77As (0.683MeV β−, 38.8h) have nuclear properties useful for positron emission tomography (PET) and radiotherapy applications, respectively. Their half-lives are sufficiently long for targeting tumors with antibodies, as well as peptides. Potential radiopharmaceuticals based on radioarsenic require development of suitable bifunctional chelates for stable conjugation of arsenic to vectors under in vivo conditions at high dilution. MethodsThe thiophilic nature of arsenic led to the synthesis and characterization of a simple trithiol ligand and its arsenic complex, and radiolabeling studies at the no carrier added (NCA) 77As level. Results1H- and 13C-NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and single crystal X-ray diffraction were used to characterize the trithiol ligand and its arsenic(III) complex. Radiotracer studies with no carrier added (NCA) 77As resulted in high radiolabeling yields (>96%) with high in vitro stability. ConclusionsThe high yield and stability of a single NCA 77As trithiol complex indicates that this framework is suitable for developing matched pair agents for non-invasive in vivo PET imaging and radiotherapy of tumors with 72,77As. This is the first reported chelate developed for NCA radioarsenic and studies are underway for developing a trithiol bifunctional chelate conjugated to a targeting vector, such as a peptide or monoclonal antibody.

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia.

Objective:Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner.Methods:Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time.Results:SUVmaxSUVmax or T/B between 2D FBP, exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms.Conclusion:Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are SUVmax or T/B between 2D FBP, consistent with other published studies however more specimens are required for full validation.

Feasibility Study on Silicon Photomultiplier With Epitaxial Quenching Resistors as the Readout for PET Detectors

The silicon photomultiplier (SiPM) with epitaxial quenching resistors (EQR) is a novel SiPM technology currently under research and development. It has distinguished features of simple device structure, high fill factor, high microcell density, large dynamic range, and fast recovery time. In this paper, we report its latest developments aiming at positron emission tomography (PET) applications. The EQR type SiPM with active area of $2.2~\hbox{mm} \times 2.2~\hbox{mm}$ demonstrated a peak PDE of 11.6% at 460 nm, PDE greater than 8.0% at 420 nm, temperature coefficient for breakdown voltage of 16 mV per $^\circ {\rm C}$ , with the fill factor of 40% and microcell density as high as $\sim 9000/\hbox{mm}^{2}$ . We measured a time resolution better than 357 ps FWHM and a 17.5% FWHM energy resolution at 511 keV by 1-to-1 coupling of the device with a $2~\hbox{mm} \times 2~\hbox{mm} \times 10~\hbox{mm}$ lutetium yttrium oxyorthosilicate (LYSO) crystal without any preamplifiers. Those preliminary results show the potential of using such SiPM to build a high spatial resolution and high timing resolution PET system.

(18)F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography.

Diverse radiochemistry is an essential component of nuclear medicine; this includes imaging techniques such as positron emission tomography (PET). As such, PET can track diseases at an early stage of development, help patient care planning through personalized medicine and support drug discovery programs. Fluorine-18 is the most frequently used radioisotope in PET radiopharmaceuticals for both clinical and preclinical research. Its physical and nuclear characteristics (97% β(+) decay, 109.8 min half-life, 635 keV positron energy) and high specific activity make it an attractive nuclide for labeling and molecular imaging. Arenes and heteroarenes are privileged candidates for (18)F-incorporation as they are metabolically robust and therefore widely used by medicinal chemists and radiochemists alike. For many years, the range of (hetero)arenes amenable to (18)F-fluorination was limited by the lack of chemically diverse precursors, and of radiochemical methods allowing (18)F-incorporation in high selectivity and efficiency (radiochemical yield and purity, specific activity, and radio-scalability). The appearance of late-stage fluorination reactions catalyzed by transition metal or small organic molecules (organocatalysis) has encouraged much research on the use of these activation manifolds for (18)F-fluorination. In this piece, we review all of the reactions known to date to install the (18)F substituent and other key (18)F-motifs (e.g., CF3, CHF2, OCF3, SCF3, OCHF2) of medicinal relevance onto (hetero)arenes. The field has changed significantly in the past five years, and the current trend suggests that the radiochemical space available for PET applications will expand rapidly in the near future.

(18)F]-Group 13 fluoride derivatives as radiotracers for positron emission tomography.

The field of (18)F chemistry is rapidly expanding because of the use of this radionuclide in radiotracers for positron emission tomography (PET). Until recently, most [(18)F]-radiotracers were generated by the direct attachment of (18)F to a carbon in the organic backbone of the radiotracer. The past decade has witnessed the emergence of a new strategy based on the formation of an (18)F-group 13 element bond. This approach, which is rooted in the field of fluoride anion complexation/coordination chemistry, has led to the development of a remarkable family of boron, aluminium and gallium [(18)F]-fluoride anion complexing agents which can be conjugated with peptides and small molecules to generate disease specific PET radiotracers. This review is dedicated to the chemistry of these group 13 [(18)F]-fluorides anion complexing agents and their use in PET. Some of the key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands. In addition to describing how these moieties can be converted into their [(18)F]-analogs, this review also dicusses their incorporation into bioconjugates for application in PET.