PET imaging

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Positron range in PET imaging: an alternative approach for assessing and correcting the blurring

Positron range in PET imaging: an alternative approach for assessing and correcting the blurring

Submitted to: Physics in Medicine and Biology 1. Introduction Because of the improving spatial resolution of the physical detectors, the distance from positron emission to positron annihilation (positron range) is becoming a factor of increasing importance for the spatial resolution of positron emission tomography (PET). Positron range introduces uncertainty in the position of the positron emitter, resulting in blurring of the PET images. This effect is very clearly seen for high-energy emitters such as 82 Rb, but also for less energetic emitters in small-animal PET imaging where blurring on a millimetre
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[18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer

[18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer

The [ 18 F]ML-10 radiotracer is highly stable in vivo and presents a rapid clearance from non-targeted organs and a favorable dosimetry profile [ 19 ]. Several clinical trials have recently evaluated [ 18 F]ML-10 for early detection of response to radiation therapy in patients with brain me- tastases [ 20 , 21 ]. In those studies, early treatment- induced changes in the [ 18 F]ML-10 tumor accumulation were measured by voxel-based analysis and correlated with changes in anatomical dimensions, as visualized with magnetic resonance imaging (MRI). The authors confirmed the value of PET imaging with [ 18 F]ML-10 for early assessment of tumor response to therapy as well as the potential of this radiotracer to visualize apop- tosis. In addition, studies in two types of solid tumors (nasopharyngeal carcinoma and head/neck carcinoma) have also highlighted the capacity of the [ 18 F]ML-10 ra- diotracer to target apoptotic cells following cancer chemotherapy [ 22 , 23 ]. However, no pre-clinical or clin- ical studies have been conducted in TNBC models.
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Clinical utility of amyloid PET imaging in the differential diagnosis of atypical dementias and its impact on caregivers

Clinical utility of amyloid PET imaging in the differential diagnosis of atypical dementias and its impact on caregivers

14 DISCUSSION This study investigated the clinical utility of amyloid PET imaging in the differential diagnosis of early-onset atypical cases of dementia. It demarcated itself from previous work in two ways. First, by defining ‘uncertainty after a comprehensive assessment’ (see AUC criteria (Johnson, 2013)) as an “uncertain diagnosis after history taking, neurological examination, blood tests, comprehensive neuropsychological examination, MRI – dementia protocol and FDG-PET”, therefore recruiting the most challenging atypical cases. Second, it addressed impact on caregivers using a 21-item Likert scale questionnaire and a 1-hour interview specifically designed for this study. Amyloid PET was associated with a diagnostic change in 9/28 cases (32.1%). There was a 44% increase in diagnostic confidence. Altered management occurred in 71.4% (20/28) of cases. Knowledge of amyloid status improved caregivers’ outcomes in all domains (anxiety, depression, disease perception, future anticipation, and quality of life). Altogether, our results suggested a useful and additive role for amyloid PET in atypical cases with an unclear diagnosis beyond the detailed workup of a tertiary memory clinic. Amyloid PET increased diagnostic confidence and generated clinically significant alterations in management. The overall process was positive for caregivers notably by making it easier to spend quality time with their loved ones.
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Optimization of brain PET imaging for a multicentre trial: the French CATI experience

Optimization of brain PET imaging for a multicentre trial: the French CATI experience

Several large cohort studies on AD have been launched since the early 2000s. Among them, ADNI-1 was a forward-thinking, imaging-based multicentre clinical trial that in- volved 50 centres in North America, with the aim of identifying biomarkers of AD. For the PET imaging carried out in this study, the ADNI PET core determined reconstruc- tion parameters for each scanner model and 3D-Hoffman phantoms were acquired with a standard protocol. However, discrepancies between the image characteristics from different PET centres remained high and were accounted for by degrading the spatial resolution to the lowest value among centres [1].
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Development of a new radiofluorinated quinoline analog for PET imaging of phosphodiesterase 5 (PDE5) in brain

Development of a new radiofluorinated quinoline analog for PET imaging of phosphodiesterase 5 (PDE5) in brain

hydrolysing the second messengers cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) throughout the body and brain. Altered cyclic nucleotide- mediated signalling has been associated with a wide array of disorders, including neurodegenerative disorders . Recently, PDE5 has been shown to be involved in neurodegenerative disorders such as Alzheimer's disease but its precise role has not been elucidated yet. To visualize and quantify the expression of this enzyme in brain, we developed a radiotracer for specific PET imaging of PDE5. A quinoline based lead compound has been structurally modified resulting in the fluoroethoxymethyl derivative ICF24027 with high inhibitory activity towards PDE5 (IC 50 = 1.86 nM). Radiolabelling with
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Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

For in vivo PET imaging, whole-body scans were acquired using a small-animal device (eXplore Vista, GE Healthcare). Acquisition (30 minutes duration, 2 bed positions) was performed with a 250 to 700 keV energy window set and 6-nanosecond coincidence time window. Images were reconstructed using a two-dimensional ordered subset expectation maximization (Fourier rebinning) method including corrections for scanner dead time, scatter radiations and randoms. Tracer uptake was quantified from in vivo scans with eXplore Vista software package (GE Healthcare), with volume of interest delineated over tumor and muscle (considered as background): the mean counts per pixel per minute per ml of tissue were obtained and expressed as percentage of injected dose per g (%ID/g). In vivo tumor to background ratio was calculated by dividing the %ID/g value of tumor by the %ID/g value of muscle.
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Automated radiosynthesis of 1-(2-[18F]fluoroethyl)-tryptophan, a potential substrate for indoleamine 2,3-dioxygenase PET imaging

Automated radiosynthesis of 1-(2-[18F]fluoroethyl)-tryptophan, a potential substrate for indoleamine 2,3-dioxygenase PET imaging

[6] Dolušić E.; Frédérick R.; & al. (2011) Eur. J. Med. Chem., 46, 3058-3065. [7] Dolušić E.; Frédérick R.; & al. (2011) J. Med. Chem., 54, 5320-5334. Automated radiosynthesis of 1-(2-[ 18 F]fluoroethyl)- tryptophan, a potential substrate for indoleamine 2,3-dioxygenase PET imaging

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Development of New Radiotracers for PET Imaging of Adrenomedullin and Angiotensin II Type 1 Receptors

Development of New Radiotracers for PET Imaging of Adrenomedullin and Angiotensin II Type 1 Receptors

11 distribution within tissues. This information, when combined with assumptions based on physiology or biochemical models, can be used to assess biological processes in vivo. In a PET camera, when opposing 511 keV gamma rays reach simultaneously two detector crystals, a flash of light (scintillation) is produced and due to the photoelectric effect, released electrons then magnified their energy in a photomultiplier tube [24] (Figure 6). By processing the information of millions of annihilations using mathematical techniques, a map of the activity distribution within the field of view over time is generated producing a dynamic image and time- activity curve (TAC) for various regions of interest (ROI) in the subject (Figure 6) [25]. Combining the maximal positron range (which is unique for each radioisotope) with the crystal detector properties and its photomultiplier tube, determine the final resolution of PET images (typically 4- 6 mm). Recently, the spatial resolution of newer clinical systems (mainly dedicated for brain imaging) has been improved up to 2.5 mm and for small animal PET imaging systems, resolutions of 0.8-1.5 mm can be achieved [26].
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Calculating an estimate of tissue integrated activity in 18F-FDG PET imaging using one SUV value.

Calculating an estimate of tissue integrated activity in 18F-FDG PET imaging using one SUV value.

based’ dosimetric approaches are usually considered as sufficient to deduce a first order estimate of irradiation induced by the nuclear medicine procedure [6]. How- ever, even in current clinical 18 F-FDG PET imaging, get- ting a better estimate (i.e. more patient-specific) of the absorbed dose may be relevant, although the only avail- able parameter for 18 F-FDG uptake is semi-quantitative, i.e. the standardized uptake value (SUV) index. As an ex- ample, a first estimation has been made a posteriori by Zanotti-Fregonara et al. (Z-F) for an 18 F-FDG examin- ation accidentally performed during pregnancy [7,8]. It could also be helpful for epidemiologic purpose such as in patients having undergone numerous examinations.
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The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

understanding of the fundamental biological processes and helps to diagnose various diseases successfully [2] and [3]. It is difficult to obtain all the necessary information about the biological structure and function of an organ by any single imaging modality among all the existing imaging techniques. Therefore attempts are being made to fuse the advantages of different imaging techniques by combining two or more imaging modalities while eliminating or reducing their disadvantages. Thus dual or multimodal imaging methods are used to enhance the quality of the images to achieve proper visualization of the organs and a better reliability of the collected data. Multimodal contrast agents are becoming increasingly important for biomedical applications. A variety of combinations of different modalities including MRI –optical, PET–near-infrared optical fluorescence (NIRF) and PET –CT have been reported [1], [4], [5], [6], [7] and [8]. The fusion of PET and MRI in a single contrast agent has proved to be beneficial as it gives images of high sensitivity and high resolution [1]. For example, the low sensitivity of magnetic resonance imaging (MRI) is often found insufficient for detection of tissue injury, assessment of tissue/organ function and more recently for tracking of implanted stem cells. To overcome this limitation of low sensitivity, a number of contrast agents have been developed, however, these contrast agents often have to be administered in a high concentration in order to obtain clinically useful images [9], [10], [11] and [12]. On the contrary positron emission tomography (PET) has the advantage of high sensitivity and isotropism i.e., ability to detect and quantify the exogenous radioactive isotopes accurately [13]. However, the low spatial resolution of PET in comparison to MRI often makes PET imaging insufficient to obtain reliable biological information [14],
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Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

a priori spatial information. The k-means algorithm was used to ensure an unsupervised clustering and low com- putational cost. As bladder uptake is not systematically found in these procedures, our detection method could be considered a pre-processing step for PET imaging in order to enable further non-parasitized tumor quantifica- tion. From this point of view, the issue we wish to ad- dress herein is how to distinguish the bladder signal while preserving the information arising from the tumor uptake. This methodology was applied to real clinical data from a standardized clinical protocol where bladder uptake was observed in several cases.
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Automatic Classification of FDG-PET imaging data in Disorders of Consciousness

Automatic Classification of FDG-PET imaging data in Disorders of Consciousness

Automatic Classification of FDG-PET imaging data in Disorders of Consciousness Medial and lateral frontoparietal cortices and brain stem appear to play a key role in consciousness state, as shown from the weights assigned by the classifier to the voxels. Besides the absolute cortical metabolic activity [5], glucose consumption in different brain regions can affect the state of consciousness. The MCS correct classification rate is a critical point and needs to be improved. Some reasons that could develop it are:

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Radiolabeled Bombesin Analogs to Improve Prostate Cancer Diagnosis by PET Imaging

Radiolabeled Bombesin Analogs to Improve Prostate Cancer Diagnosis by PET Imaging

1.3 P OSITRON E MISSION T OMOGRAPHY (PET) I MAGING PET technique shows a promising future in the imaging of prostate cancer (Hong et al., 2010). PET imaging requires radionuclides that emit positron (β + ). Positron-emitting nuclides are generally produced using a cyclotron by bombarding target materials with protons or deuterons. The resulting nuclides are unstable and therefore, stabilize through decay by positron-emission. The positron is ejected from the nucleus and is then annihilated with a surrounding electron producing two 511 keV photons traveling in opposite directions. In the PET scanner, a ring of detectors detects those annihilation photons in coincidence. The sensitivity of PET is at least 2 orders of magnitude better than that of single photon imaging systems. Therefore, PET has the potential to play an important role in the detection of localized and metastatic prostate cancer. Short-lived organic radioisotopes such as 11 C, 13 N, 15 O and 18 F have limitations because they require fast manipulation, rapid chemical synthesis, which makes the clinical applications quite challenging and requires an on-site cyclotron for their production.
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A pretargeting system for tumor PET imaging and radioimmunotherapy

A pretargeting system for tumor PET imaging and radioimmunotherapy

To further advance the clinical applications of pretarget- ing, it also became clear that humanized recombinant bispecific antibodies must be produced. Although many different for- mats of bispecific antibodies had been proposed, mass produc- tion under GMP conditions proved quite difficult. Eventually, Immunomedics, Inc., developed a new approach they refer to as the Dock-and-Lock ™ (DNL) method ( Rossi et al., 2006 ). The DNL method uses the regulatory subunits of cAMP-dependent protein kinase and the anchoring domains of A kinase to con- struct conjugates of antibody Fab fragments that are bispecific and trivalent, with a single binding site for the hapten and two binding sites for the tumor antigen. They have successfully produced several DNL ™ conjugates binding CEA (TF2), CD20 (TF4), a mucin antigen expressed by pancreatic tumors (TF10), and the Trop-2 antigen (TF12) ( Govindan and Goldenberg, 2010; Sharkey et al., 2012 ). Through these remarkable achievements, using this technology, radionuclide pretargeting is now possible against a wide spectrum of target antigens, and allows a vari- ety of radionuclides for PET imaging and therapy to be mobi- lized ( Karacay et al., 2009; Schoffelen et al., 2010b, 2012; van Rij et al., 2013 ). The first clinical results of an optimization study assessing the anti-CEA × anti-HSG bsMAb TF2 and the radiola- beled hapten-peptide, 177 Lu-IMP288, in patients with metastatic CRC have been reported recently ( Schoffelen et al., 2013 ). Dif- ferent schedules were studied in four cohorts of five patients: (1) shortening the interval between the bsMAb and peptide admin- istration (5 days to 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the peptide dose (from 100 to 25 µ g). Rapid and selective tumor uptake was detected within 1 h after the peptide injection, with high tumor-to-tissue ratios at 24 h. The best tumor targeting was achieved with a 1-day pretar- geting interval and with the 25-µg peptide dose. High activities of 177 Lu-IMP288 (2.5–7.4 GBq) were well-tolerated, with some
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Staging of regional nodes in AJCC stage I and II melanoma: 18FDG PET imaging versus sentinel node detection.

Staging of regional nodes in AJCC stage I and II melanoma: 18FDG PET imaging versus sentinel node detection.

= 1.89 mm) scheduled for a LM/SL underwent 18 FDG PET imaging in pretreatment staging. All patients included into this institutional protocol were classified at stage I or II cutaneous melanoma (T1-4 N0 M0) according to the latest version of the American Joint Committee on Cancer (AJCC) staging system [25]. The patients with histologi- cally unproven primary melanoma or those with confirmed but more advanced disease (AJCC stages III or IV), as well as subjects previously treated for malignant melanoma or other malignancies were systematically excluded from the study group. Additionally, in our staging protocol, only the patients who underwent LM/SL within the week following the metabolic imaging were taken into account. The LM/SL technique included, in a 1-day protocol, a preoperative lym- phoscintigraphy followed by an intraoperative lymphatic mapping using gamma probe guidance. Each patient was individually followed with a median follow-up time of 12 months. Post-therapy surveillance included complete phys- ical examination at the control visits and oriented imaging
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PROGNOSTIC VALUE OF POSTTREATMENT FEDG-PET IMAGING FOLLOWING COMBINED CHEMORADIATION THERAPY IN LOCALLY ADVANCED CERVICAL CANCER

PROGNOSTIC VALUE OF POSTTREATMENT FEDG-PET IMAGING FOLLOWING COMBINED CHEMORADIATION THERAPY IN LOCALLY ADVANCED CERVICAL CANCER

Conclusions In patients treated with CT/RT for locally advanced cervical cancer, despite limited performances to predict cervical residual disease, posttreatment FEDG-PET is predictive of patients’ prognosis and long-term outcome. Our study did not show any value of posttreatment FEDG-PET for triaging patients that could benefit from completion surgery. Prospective

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Longitudinal mouse-PET imaging: a reliable method for estimating binding parameters without a reference region or blood sampling

Longitudinal mouse-PET imaging: a reliable method for estimating binding parameters without a reference region or blood sampling

The correlations between the parameters from the PET scans and the autoradiography are shown in Fig. 4 . For each time point, and over all animals at all time points, there is an increase in the correlation between the autoradiography and the PET parameter with increasing iteration, which plateaus around 10 iterations. Looking at the %ID for 0 and 10 iterations of 4D- RRD, the Pearson R increased by 35% by doing 4D-RRD only (from 0.53 to 0.72). Correlations are further improved using the VT value instead of the %ID with a total increase of 48% (from 0.53 to 0.79). The VT values without 4D-RRD (0 its) increased the correlation over all time points by 24% compared to %ID without 4D-RRD (from 0.66 to 0.79). The significance of the Pearson R changes depending on the method applied, giving a better indication of the strength of each method, as indicated as significance levels in Fig. 4 . The Pearson R coefficient is sig- nificant for all methods used when including all time points at once (7 regions at 4 time points = 28 correlation points). Looking at the individual time points (7 regions = 7 correlation points each), without 4D-RRD, the %ID original method only gave significant Pearson R correlations at 7 days time point, and the VT estimate without 4D-RRD was only significant at the 1- month time point. Applying 4D-RRD generally produced sig- nificant Pearson R coefficients, except for the Baseline group, where only the 4D-RRD with 15 iterations had a significant Pearson R.
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Impact of respiratory motion correction on the detection of small lesions in whole-body PET imaging: A simulation study

Impact of respiratory motion correction on the detection of small lesions in whole-body PET imaging: A simulation study

S. Marache-Francisco, Member IEEE , F. Lamare, H. Fayad, Member IEEE, D. Visvikis, Senior Member IEEE, R. Prost, Member IEEE, J.-M. Rouet, C. Lartizien  Abstract–Respiratory motion in Positron Emission Tomography leads to reduced image quality, influencing this way the quantitative accuracy of PET measurements, as shown in numerous studies. However, only few results have been published on its impact on lesion detection. This study intends to evaluate the impact of motion correction on the detection of small lesions (between 8 and 12 mm diameter) using a Computed-Aided Detection (CAD) system on FDG whole-body simulated PET images. We evaluate two types of motion correction techniques, both using motion fields derived from the reconstruction of gated PET images. The first technique consists in averaging the co- registered gated reconstructed PET images, while the second method integrates the motion fields during the iterative reconstruction process.
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Increased expression of "peripheral-type" benzodiazepine receptors in human temporal lobe epilepsy: implications for PET imaging of hippocampal sclerosis

Increased expression of "peripheral-type" benzodiazepine receptors in human temporal lobe epilepsy: implications for PET imaging of hippocampal sclerosis

Neurobiol. 9:207–227. Johnson, E.W., de Lanerolle, N.C., Kim, J.H., Sundaresan, S., Spencer, D.D., Mattson, R.H., Zoghbi, S.S., Baldwin, R.M., Hoffer, P.B., and Seibyl, J.P. (1992). “Central” and “peripheral” benzodiazepine receptors: Opposite changes in human epileptogenic tissue. Neurology 42:811–815. Koepp, M.J., Hammers, A., Labbe, C., Woerman, F.G., Brooks, D.J., and Duncan, J.S. (2000). 11C- Flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI. Neurology 54:332–339.

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View of Understanding Positron Emission Tomography (PET) Imaging

View of Understanding Positron Emission Tomography (PET) Imaging

4. Tournier N, Goutal S, Auvity S, Traxl A, Mairinger S, Wanek T, Helal OB, Buvat I, Soussan M, Caillé F, Langer O, (2017) Strate- gies to inhibit ABCB1- and ABCG2-mediated efflux transport of erlotinib at the blood-brain barrier: a PET study on nonhuman pri- mates. J Nucl Med 58: 117 –122. doi:10.2967/jnumed.116.178665 5. Tournier N, Stieger B, Langer O, (2018) Imaging techniques to study drug transporter function in vivo. Pharmacol Therapeut 189: 104 –122. doi:10.1016/j.pharmthera.2018.04.006

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