Publications by authors named "Katherine Zukotynski"

84 Publications

Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer.

Can Urol Assoc J 2021 Mar 1. Epub 2021 Mar 1.

Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is increasingly being used worldwide as part of the clinical workup for men with prostate cancer. With high overall accuracy for the detection of prostate cancer, PSMA-targeted PET has an increasingly established role in the setting of biochemical failure after primary therapy and an evolving role in the setting of initial disease staging; its utility for guiding management in the setting of metastatic disease is less clear. Although the specificity is high, familiarization with potential pitfalls in the interpretation of PSMA-targeted PET, including knowledge of the causes for false positive and negative examinations, is critical. The aim of this article is to provide an illustrative discussion of the current and evolving clinical indications for PSMA-targeted PET, as well as a review of physiologic radiopharmaceutical biodistribution and potential imaging pitfalls.
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http://dx.doi.org/10.5489/cuaj.7268DOI Listing
March 2021

Radiographic and metabolic evolution of prostate cancer lung metastasis detected by prostate-specific membrane antigen and fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography.

World J Nucl Med 2020 Oct-Dec;19(4):421-424. Epub 2020 Sep 14.

School of Medicine, McMaster University, Hamilton, Ontario, Canada.

We describe the case of a 75-year-old patient who progressed over a 12-year period from localized to symptomatic metastatic prostate cancer (PrCa) with lung as the sole organ of involvement. In this case, the specific sequence of positron emission tomography (PET)-based next-generation imaging with F-sodium fluoride-, F-fluoro-2-deoxy-D-glucose-, and F-DCFPyL PET/computed tomography and biopsies allowed illustration of the pathway of disease progression from nonglycolytic hormone-sensitive PrCa to glycolytic castrate-resistant PrCa without neuroendocrine features. The observations provide a unique insight into the timelines of anatomical and metabolic progression of metastatic PrCa. They highlight the value of close radiographic surveillance of metastatic PrCa with modern imaging to guide early treatment interventions.
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http://dx.doi.org/10.4103/wjnm.WJNM_17_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875042PMC
September 2020

Prospective, Single-Arm Trial Evaluating Changes in Uptake Patterns on Prostate-Specific Membrane Antigen (PSMA)-Targeted F-DCFPyL PET/CT in Patients with Castration-Resistant Prostate Cancer Starting Abiraterone or Enzalutamide.

J Nucl Med 2021 Feb 19. Epub 2021 Feb 19.

Johns Hopkins University School of Medicine, United States.

Positron emission tomography (PET) with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer (PCa) imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. This prospective, single-arm, two-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer (CRPC) initiating abiraterone or enzalutamide. Each patient was imaged with F-DCFPyL at baseline and within 2-4 months after starting therapy. Patients were followed for up to 48 months from enrollment. A central review evaluated baseline and follow-up PET scans recording change in maximum standardized uptake value (SUV) at all disease sites and classifying the pattern of change. Two parameters: the delta percent SUV (DPSM) of all lesions and the delta absolute SUV (DASM) of all lesions were derived. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 months (95% confidence interval (CI), 6.9-14.2) and median OS was 28.6 months (95% CI 18.3-not available (N/A)). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had shorter TTTC and OS. Men with low DPSM had median TTTC 12.2 months (95% CI 11.3-N/A) and median OS 37.2 months (95% CI 28.9-N/A), while those with high DPSM had median TTTC 6.5 months (95% CI 4.6-N/A, = 0.0001) and median OS 17.8 months (95% CI 13.9-N/A, = 0.02). Men with low DASM had median TTTC 12.2 months (95% CI 11.3-N/A) and median OS N/A (95% CI 37.2 months-N/A), while those with high DASM had median TTTC 6.9 months (95% CI 6.1-N/A, = 0.003) and median OS 17.8 months (95% CI 13.9-N/A, = 0.002). Findings on PSMA-targeted PET 2-4 months after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions and/or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.
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http://dx.doi.org/10.2967/jnumed.120.259069DOI Listing
February 2021

CCCDTD5: Clinical role of neuroimaging and liquid biomarkers in patients with cognitive impairment.

Alzheimers Dement (N Y) 2020 22;6(1):e12098. Epub 2021 Jan 22.

Centre hospitalier de l'université de Montréal Montreal Canada.

Since 1989, four Canadian Consensus Conferences on the Diagnosis and Treatment of Dementia (CCCDTDs) have provided evidence-based dementia diagnostic and treatment guidelines for Canadian clinicians and researchers. We present the results from the Neuroimaging and Fluid Biomarkers Group of the 5th CCCDTD (CCCDTD5), which addressed topics chosen by the steering committee to reflect advances in the field and build on our previous guidelines. Recommendations on Imaging and Fluid Biomarker Use from this Conference cover a series of different fields. Prior structural imaging recommendations for both computerized tomography (CT) and magnetic resonance imaging (MRI) remain largely unchanged, but MRI is now more central to the evaluation than before, with suggested sequences described here. The use of visual rating scales for both atrophy and white matter anomalies is now included in our recommendations. Molecular imaging with [F]-fluorodeoxyglucose ([18F]-FDG) Positron Emisson Tomography (PET) or [Tc]-hexamethylpropyleneamine oxime/ethylene cysteinate dimer ([Tc]-HMPAO/ECD) Single Photon Emission Tomography (SPECT), should now decidedly favor PET. The value of [F]-FDG PET in the assessment of neurodegenerative conditions has been established with greater certainty since the previous conference, and it has now been recognized as a useful biomarker to establish the presence of neurodegeneration by a number of professional organizations around the world. Furthermore, the role of amyloid PET has been clarified and our recommendations follow those from other groups in multiple countries. SPECT with [I]-ioflupane (DaTscan) is now included as a useful study in differentiating Alzheimer's disease (AD) from Lewy body disease. Finally, liquid biomarkers are in a rapid phase of development and, could lead to a revolution in the assessment AD and other neurodegenerative conditions at a reasonable cost. We hope these guidelines will be useful for clinicians, researchers, policy makers, and the lay public, to inform a current and evidence-based approach to the use of neuroimaging and liquid biomarkers in clinical dementia evaluation and management.
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http://dx.doi.org/10.1002/trc2.12098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821956PMC
January 2021

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of F-DCFPyL PET/CT Restaging.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100553. Epub 2020 Sep 9.

Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre and Western University, London, Canada.

Purpose: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy.

Methods And Materials: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT.

Results: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months.

Conclusions: Most patients had a major change in actual management compared with pre-PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.
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http://dx.doi.org/10.1016/j.adro.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820022PMC
September 2020

Prostate-specific membrane antigen targeted PET/CT for recurrent prostate cancer: a clinician's guide.

Expert Rev Anticancer Ther 2021 Feb 8:1-15. Epub 2021 Feb 8.

Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre , London, Ontario, Canada.

Introduction: PSMA-targeted PET/CT is a 'Next Generation Imaging' technique with superior sensitivity and specificity for detecting recurrent prostate cancer compared with conventional imaging, allowing more accurate staging and re-staging.

Areas Covered: This article reviews the role of PSMA-targeted PET/CT in clinical management of men with recurrent prostate cancer.

Expert Opinion: Through enhanced spatial characterization of recurrent prostate cancer, PSMA-targeted PET/CT has shown significant impact on management decisions. In particular, by identifying men with recurrence confined to the prostate or pelvic nodes, PSMA-targeted PET/CT enables selective deployment of localized salvage therapies for management of biochemical failure after primary treatment with prostatectomy or radiotherapy. In oligometastatic disease, PSMA-targeted PET/CT may improve patient selection and treatment accuracy for metastasis-directed therapy and early phase II studies show encouraging results in delaying the need for systemic therapy. Further, quantitative PSMA-targeted PET/CT for monitoring response and therapeutic PSMA-targeted radiopharmaceuticals are emerging as encouraging treatment options in the setting of castrate-resistant disease.
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http://dx.doi.org/10.1080/14737140.2021.1878883DOI Listing
February 2021

Case - F-DCFPyL-positron emission tomography/computed tomography (PET/CT) time of imaging.

Can Urol Assoc J 2020 Dec 15. Epub 2020 Dec 15.

Department of Medicine and Radiology, McMaster University, Hamilton, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.6984DOI Listing
December 2020

Mars Shot for Nuclear Medicine, Molecular Imaging, and Molecularly Targeted Radiopharmaceutical Therapy.

J Nucl Med 2021 Jan;62(1):6-14

Departments of Radiology and Physics, University of Iowa, Iowa City, Iowa.

The Society of Nuclear Medicine and Molecular Imaging created the Value Initiative in 2017 as a major component of its strategic plan to further demonstrate the value of molecular imaging and molecularly targeted radiopharmaceutical therapy to patients, physicians, payers, and funding agencies. The research and discovery domain, 1 of 5 under the Value Initiative, has a goal of advancing the research and development of diagnostic and therapeutic nuclear medicine. Research and discovery efforts and achievements are essential to ensure a bright future for NM and to translate science to practice. Given the remarkable progress in the field, leaders from the research and discovery domain and society councils identified 5 broad areas of opportunity with potential for substantive growth and clinical impact. This article discusses these 5 growth areas, identifying specific areas of particularly high importance for future study and development. As there was an understanding that goals should be both visionary yet achievable, this effort was called the Mars shot for nuclear medicine.
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http://dx.doi.org/10.2967/jnumed.120.253450DOI Listing
January 2021

Overview of the First NRG-NCI Workshop on Dosimetry of Systemic Radiopharmaceutical Therapy (RPT).

J Nucl Med 2020 12 4. Epub 2020 Dec 4.

McMaster University.

In 2018, the National Cancer Institute (NCI) and the NRG Oncology partnered for the first time to host a joint Workshop on Systemic Radiopharmaceutical Therapy (RPT) to specifically address issues and strategies of dosimetry for future clinical trials. The workshop focused on (1) current dosimetric approaches for clinical trials, (2) strategies under development that would provide optimal dose reporting, and (3) future desired/optimized approaches for the new and novel emerging radionuclides and carriers in development. In this proceedings, we review the main approaches that are applied clinically to calculate the absorbed dose: These include absorbed doses calculated over a variety of spatial scales including organ, suborgan, and voxel, all achievable within the Medical Internal Radiation Dose (MIRD) schema (S-value) can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This proceeding will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biological effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We will also discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation-when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.
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http://dx.doi.org/10.2967/jnumed.120.255547DOI Listing
December 2020

Internal Jugular Vein and Cerebral Venous Sinus Infective Thrombophlebitis Detected With 99mTc-HMPAO White Blood Cell Scintigraphy.

Clin Nucl Med 2021 Feb;46(2):e112-e113

Nuclear Medicine, Western University, London.

Abstract: A 35-year-old man with a history of renal transplant, congenital cystinosis, and diabetes was admitted to the hospital with fever, bilateral parotid gland swelling, and acute renal failure. He had 99mTc-HMPAO-WBC (99mTc-hexamethylpropyleneamineoxime white blood cell) imaging for the evaluation of possible parotitis. There was intense radiopharmaceutical uptake along the right internal jugular vein extending to the right sigmoid and transverse and superior sagittal sinuses, suggestive of infective thrombophlebitis or Lemierre syndrome. This study illustrates the value of 99mTc-HMPAO-WBC imaging as a tool for evaluating thrombophlebitis, particularly in patients with renal failure in whom contrast-enhanced CT may not be possible.
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http://dx.doi.org/10.1097/RLU.0000000000003352DOI Listing
February 2021

Machine Learning in Nuclear Medicine: Part 2-Neural Networks and Clinical Aspects.

J Nucl Med 2021 Jan 25;62(1):22-29. Epub 2020 Sep 25.

Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

This article is the second part in our machine learning series. Part 1 provided a general overview of machine learning in nuclear medicine. Part 2 focuses on neural networks. We start with an example illustrating how neural networks work and a discussion of potential applications. Recognizing that there is a spectrum of applications, we focus on recent publications in the areas of image reconstruction, low-dose PET, disease detection, and models used for diagnosis and outcome prediction. Finally, since the way machine learning algorithms are reported in the literature is extremely variable, we conclude with a call to arms regarding the need for standardized reporting of design and outcome metrics and we propose a basic checklist our community might follow going forward.
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http://dx.doi.org/10.2967/jnumed.119.231837DOI Listing
January 2021

Histologic Validation of F-DCFPyL PET/CT with Comparison to Multiparametric MRI in Biochemically Recurrent Prostate Cancer.

Radiology 2020 09 7;296(3):573-574. Epub 2020 Jul 7.

Departments of Radiology and Medicine, McMaster University, 1200 Main St W, Room 1P11, Hamilton, ON, Canada L8N 3Z5 (K.A.Z.); and Departments of Radiology, Oncology and Urology, Johns Hopkins University School of Medicine, Baltimore, Md (S.P.R.).

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http://dx.doi.org/10.1148/radiol.2020202098DOI Listing
September 2020

Prostate Cancer Lymphangitic Pulmonary Carcinomatosis: Appearance on 18F-FDG PET/CT and 18F-DCFPyL PET/CT.

Clin Nucl Med 2020 Sep;45(9):727-729

Department of Oncology, Western University, London, Ontario, Canada.

A 51-year-old man diagnosed with high-grade, high-volume metastatic castration-sensitive prostate adenocarcinoma received pelvic radiation, androgen deprivation therapy, and intravenous docetaxel. Serum prostate-specific antigen became undetectable following treatment. Within a year, his cancer progressed to castration-resistant disease, and he was treated with oral abiraterone acetate 1000 mg and prednisone 10 mg daily. Despite this, the serum prostate-specific antigen rose from 0.03 to 1.39 μg/L, and F-DCFPyL and F-FDG PET/CT showed progression. While F-DCFPyL uptake may be seen in aggressive disease, F-FDG portends poor prognosis. Despite intravenous platinum-based chemotherapy, the patient died of respiratory failure 20 months after his initial diagnosis.
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http://dx.doi.org/10.1097/RLU.0000000000003109DOI Listing
September 2020

The Use of Random Forests to Identify Brain Regions on Amyloid and FDG PET Associated With MoCA Score.

Clin Nucl Med 2020 Jun;45(6):427-433

Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.

Purpose: The aim of this study was to evaluate random forests (RFs) to identify ROIs on F-florbetapir and F-FDG PET associated with Montreal Cognitive Assessment (MoCA) score.

Materials And Methods: Fifty-seven subjects with significant white matter disease presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial, had MoCA and F-florbetapir PET; 55 had F-FDG PET. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter (F-florbetapir PET), or pons (F-FDG PET). SUV ratio data and MoCA score were used for supervised training of RFs programmed in MATLAB.

Results: F-Florbetapir PETs were randomly divided into 40 training and 17 testing scans; 100 RFs of 1000 trees, constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: right posterior cingulate gyrus, right anterior cingulate gyrus, left precuneus, left posterior cingulate gyrus, and right precuneus. Amyloid increased with decreasing MoCA score. F-FDG PETs were randomly divided into 40 training and 15 testing scans; 100 RFs of 1000 trees, each tree constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: left fusiform gyrus, left precuneus, left posterior cingulate gyrus, right precuneus, and left middle orbitofrontal gyrus. F-FDG decreased with decreasing MoCA score.

Conclusions: Random forests help pinpoint clinically relevant ROIs associated with MoCA score; amyloid increased and F-FDG decreased with decreasing MoCA score, most significantly in the posterior cingulate gyrus.
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http://dx.doi.org/10.1097/RLU.0000000000003043DOI Listing
June 2020

Safety of the Use of Radioactive Iodine in Patients With Hyperthyroidism.

JAMA Intern Med 2019 12;179(12):1738-1739

American College of Nuclear Medicine, North Augusta, South Carolina.

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http://dx.doi.org/10.1001/jamainternmed.2019.5120DOI Listing
December 2019

A Prospective Study of 18F-DCFPyL PSMA PET/CT Restaging in Recurrent Prostate Cancer following Primary External Beam Radiotherapy or Brachytherapy.

Int J Radiat Oncol Biol Phys 2020 03 12;106(3):546-555. Epub 2019 Nov 12.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre and Western University, London, Canada. Electronic address:

Purpose: Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease.

Methods And Materials: A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized.

Results: Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients.

Conclusions: 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.001DOI Listing
March 2020

Fifth Anniversary of SNMMI Professional Relations Fellowship.

J Nucl Med 2019 Sep;60(9):20N

McMaster University, Hamilton, ON.

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September 2019

The Use of Random Forests to Classify Amyloid Brain PET.

Clin Nucl Med 2019 Oct;44(10):784-788

Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.

Purpose: To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification.

Methods: The data set included 57 baseline F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive). SUV ratio data and clinical reads were used for supervised training of an RF classifier programmed in MATLAB.

Results: A 10,000-tree RF, each tree using 15 randomly selected cases and 20 randomly selected features (SUV ratio per region of interest), with 37 cases for training and 20 cases for testing, had sensitivity = 86% (95% confidence interval [CI], 42%-100%), specificity = 92% (CI, 64%-100%), and classification accuracy = 90% (CI, 68%-99%). The most common features at the root node (key regions for stratification) were (1) left posterior cingulate (1039 trees), (2) left middle frontal gyrus (1038 trees), (3) left precuneus (857 trees), (4) right anterior cingulate gyrus (655 trees), and (5) right posterior cingulate (588 trees).

Conclusions: Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.
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http://dx.doi.org/10.1097/RLU.0000000000002747DOI Listing
October 2019

Clinical and Technical Considerations for Brain PET Imaging for Dementia.

J Nucl Med Technol 2020 Mar 10;48(1):5-8. Epub 2019 Jun 10.

Department of Radiology, University of Tennessee Medical Center, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee.

The number of cases of dementia has dramatically increased over the last decade. Imaging of the brain with PET has been used for many years, but in the past decade the radiopharmaceuticals and technology available for imaging dementia have vastly improved. In recent years, the U.S. Food and Drug Administration has approved 3 PET radiopharmaceuticals for detecting amyloid in brain, and tau PET radiopharmaceuticals are being investigated in clinical trials for use in dementia imaging. This paper will discuss different forms of dementia that can be imaged with PET, review common radiopharmaceuticals used for imaging dementia, and provide technical recommendations for performing the studies.
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http://dx.doi.org/10.2967/jnmt.118.220087DOI Listing
March 2020

An International Survey of PET/CT Clinical Reporting.

J Nucl Med 2019 Apr 15;60(4):478-479. Epub 2019 Mar 15.

Department of Diagnostic Imaging, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

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http://dx.doi.org/10.2967/jnumed.118.223073DOI Listing
April 2019

Machine Learning in Nuclear Medicine: Part 1-Introduction.

J Nucl Med 2019 04 7;60(4):451-458. Epub 2019 Feb 7.

Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; and

This article, the first in a 2-part series, provides an introduction to machine learning (ML) in a nuclear medicine context. This part addresses the history of ML and describes common algorithms, with illustrations of when they can be helpful in nuclear medicine. Part 2 focuses on current contributions of ML to our field, addresses future expectations and limitations, and provides a critical appraisal of what ML can and cannot do.
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http://dx.doi.org/10.2967/jnumed.118.223495DOI Listing
April 2019

Use of a Qualification Phantom for PET Brain Imaging in a Multicenter Consortium: A Collaboration Between the Pediatric Brain Tumor Consortium and the SNMMI Clinical Trials Network.

J Nucl Med 2019 05 7;60(5):677-682. Epub 2018 Dec 7.

Department of Radiology, Harvard Medical School, Boston, Massachusetts.

The purpose of this study was to assess image quality and quantitative brain PET across a multicenter consortium. All academic centers and children's hospitals in the Pediatric Brain Tumor Consortium (PBTC) scanned a phantom developed by the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network (SNMMI CTN) for the validation of brain PET studies associated with clinical trials. The phantom comprises 2 separate, fillable sections: a resolution/uniformity section and a clinical simulation section. The resolution/uniformity section is a cylinder 12.7 cm long and 20 cm in diameter; spatial resolution is evaluated subjectively with 2 sets of rods (hot and cold) of varying diameter (4.0, 5.0, 6.25, 7.81, 9.67, and 12.2 mm) and spacing (twice the rod diameter). The clinical simulation section simulates a transverse section of midbrain with ventricles and gray and white matter compartments. If properly filled, hot rods have a 4:1 target-to-background ratio, and gray-to-white matter sections have a 4:1 ratio. Uniformity and image quality were evaluated using the SUV in a small volume of interest as well as subjectively by 2 independent observers using a 4-point scale. Eleven PBTC sites scanned the phantom on 13 PET scanners. The phantom's complexity led to suboptimal filling, particularly of the hot rod section, in 5 sites. The SUV in the uniformity section was within 10% of unity on only 5 of 13 scanners, although 12 of 13 were subjectively judged to have very good to excellent uniformity. Four of 6 hot rods were discernable by all 13 scanners, whereas 3 of 6 cold rods were discernable by only 5 scanners. Four of 13 scanners had a gray-to-white matter ratio between 3.0 and 5.0 (4.0 is truth); however, 11 of 13 scanners were subjectively judged to have very good or excellent image quality. Eleven sites were able to image a powerful phantom developed by the SNMMI CTN that evaluated image uniformity, spatial resolution, and image quality of brain PET. There was considerable variation in PET data across the PBTC sites, possibly resulting from variations in scanning across the sites due to challenges in filling the phantom.
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http://dx.doi.org/10.2967/jnumed.118.219998DOI Listing
May 2019

Update 2018: 18F-FDG PET/CT and PET/MRI in Head and Neck Cancer.

Clin Nucl Med 2018 Dec;43(12):e439-e452

R.D.N. is a Nuclear Medicine Physician, Kaiser Permanente, Santa Clara, CA.

There are recent advances, namely, a standardized method for reporting therapy response (Hopkins criteria), a multicenter prospective cohort study with excellent negative predictive value of F-FDG PET/CT for N0 clinical neck, a phase III multicenter randomized controlled study establishing the value of a negative posttherapy F-FDG PET/CT for patient management, a phase II randomized controlled study demonstrating radiation dose reduction strategies for human papilloma virus-related disease, and Food and Drug Administration approval of nivolumab for treatment of recurrent head and neck squamous cell carcinoma.
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http://dx.doi.org/10.1097/RLU.0000000000002247DOI Listing
December 2018

18F-DCFPyL PET/CT in Oncocytoma.

Clin Nucl Med 2018 Dec;43(12):921-924

London Health Sciences Centre, Ontario, Canada.

A 76-year-old man with biochemical failure after primary radiotherapy for prostate cancer had no malignant disease detected on Tc-MDP bone scan and diagnostic CT. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is overexpressed in prostate cancer cells. The PSMA-targeted F-DCFPyL PET/CT demonstrated lymph node disease and photopenic defects in the left kidney associated with a cyst and biopsy-proven oncocytoma. Prostate-specific membrane antigen is expressed in the neovasculature of several solid tumors. It has been reported that PSMA expression is seen in approximately 50% of oncocytoma versus 76% of clear cell renal carcinomas. Biopsy confirmation is needed regardless of F-DCFPyL avidity.
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http://dx.doi.org/10.1097/RLU.0000000000002301DOI Listing
December 2018

Harmonization of United States, European Union and Canadian First-in-Human Regulatory Requirements for Radiopharmaceuticals-Is This Possible?

J Nucl Med 2018 Sep 27. Epub 2018 Sep 27.

Department of Diagnostic Imaging, Queen Elizabeth Health Sciences Center, Canada.

In recent years, several new radiotracers and radionuclide therapies have been developed. There is a renaissance in nuclear medicine and molecular imaging today, for example, in terms of the ability to image and treat neuroendocrine and prostate malignancies. In order to be able to bring a new drug product from bench to bedside and assist patients, while also ensuring patient safety, stringent regulations must be met. However, differences in regulatory requirements, often based on jurisdictional politics rather than scientific evidence, can hinder global co-operation, increase expense, and slow progress. In an effort to rise above these differences, nuclear medicine advocacy organizations, regulators, and international agencies have begun to identify commonalities in the regulations to achieve harmonization. Indeed, a more streamlined approach to radiopharmaceutical drug development across jurisdictions could be achieved through establishing harmonized requirements for pre-clinical studies and manufacturing standards. This paper provides an educational overview of the regulatory and submission requirements governing investigational radiopharmaceuticals for first-in-human radiopharmaceuticals across the European and North American continents. It is hoped that through ongoing collaboration, regulatory reform and harmonization can become a reality and speed access to the most up-to-date evidence-based patient care for all.
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http://dx.doi.org/10.2967/jnumed.118.209460DOI Listing
September 2018

PET/CT of Dementia.

AJR Am J Roentgenol 2018 08 27;211(2):246-259. Epub 2018 Jun 27.

9 Department of Medicine, Neurology Division, University of Toronto, and the Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, ON, Canada.

Objective: In this article, we review the literature on PET/CT in the management of dementia, present evidence for best clinical practices, and discuss recent advances in the field.

Conclusion: Standard-of-care imaging for dementia includes CT and MRI, primarily for excluding vascular lesions or masses, detecting atrophy, and monitoring disease severity. PET/CT is a powerful functional modality that can differentiate dementia types and influence management. Fluorine-18-FDG PET/CT reveals the spatial pattern of glucose metabolism in the brain. More recently, radiotracers for PET have been developed that bind to amyloid protein, tau protein, and neuroinflammatory markers.
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http://dx.doi.org/10.2214/AJR.18.19822DOI Listing
August 2018

A dose finding clinical trial of cabozantinib (XL184) administered in combination with abiraterone acetate in metastatic castration-resistant prostate cancer.

Prostate 2018 Jun 7. Epub 2018 Jun 7.

Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Cabozantinib can enhance the effect of abiraterone in preclinical prostate cancer models. This study aimed to define the recommended phase 2 dose (RP2D) and preliminary efficacy of abiraterone + cabozantinib in mCRPC.

Methods: Patients with progressive mCRPC with 0-2 prior chemotherapy regimens but no prior CYP17A1 or MET inhibitor received abiraterone acetate at 1000 mg daily with prednisone 5 mg BID in combination with cabozantinib at 20, 40, or 60 mg daily in a dose-escalation 3 + 3 open-label phase 1 design (Part A). After tolerable doses were defined, cohorts were expanded to better define toxicity and efficacy (Part B).

Results: There were no dose-limiting toxicities (DLTs) in the first 4 weeks at any of the three dose levels in Part A. Two of the three patients at the 60 mg dose level required dose reductions beyond cycle 2 due to fatigue. In Part B, nine more patients were accrued to each of the 20 and 40 mg doses. Of the 12 patients treated at the 40 mg dose, only one DLT (grade 3 Lipase elevation) was observed in cycle 1. The median time to radiographic progression was 12.88 months (95% CI:5.42- not estimated [NE]) in the 20 mg cohort and 22.01 months (95% CI:15.44-NE) in the 40 mg cohort. Median overall survival was 23.29 months (95% CI:19.06-NE) in the 20 mg cohort and 39.08 months (95% CI:17.38-NE) in the 40 mg cohort.

Conclusions: Based on tolerability and preliminary efficacy, 40 mg cabozantinib plus 1000 mg abiraterone daily is the RP2D.
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http://dx.doi.org/10.1002/pros.23662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286224PMC
June 2018

Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer.

Ann Intern Med 2018 03;168(6):459-460

McMaster University, Hamilton, Ontario, Canada (K.Z., C.W.).

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http://dx.doi.org/10.7326/L17-0702DOI Listing
March 2018