Radiology Commons^™

Flexible Attenuation Fields: Tomographic Reconstruction From Heterogeneous Datasets, Clifford S. Parker

Theses and Dissertations--Computer Science

Traditional reconstruction methods for X-ray computed tomography (CT) are highly constrained in the variety of input datasets they admit. Many of the imaging settings -- the incident energy, field-of-view, effective resolution -- remain fixed across projection images, and the only real variance is in the detector's position and orientation with respect to the scene. In contrast, methods for 3D reconstruction of natural scenes are extremely flexible to the geometric and photometric properties of the input datasets, readily accepting and benefiting from images captured under varying lighting conditions, with different cameras, and at disparate points in time and space. Extending CT …

Enlarged Perivascular Spaces Are A Clinically Relevant Neuroimaging Biomarker Of Cerebral Small Vessel Disease, Timothy Justin Libecap

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) represents the intersection between cerebrovascular disease and cognitive decline. Cerebral small vessel disease (cSVD) is an important risk factor that may precede the onset of VCID by years. cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) which is believed to play a role in the removal of brain waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Given the presence of ePVS in brain …

In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun

Markey Cancer Center Faculty Publications

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these post- mortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high- power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by …

Contouring Quality Assurance Methodology Based On Multiple Geometric Features Against Deep Learning Auto-Segmentation, Jingwei Duan, Mark E. Bernard, James Castle, Xue Feng, Chi Wang, Mark C. Kenamond, Quan Chen

Markey Cancer Center Faculty Publications

Background: Contouring error is one of the top failure modes in radiation treatment. Multiple efforts have been made to develop tools to automatically detect segmentation errors.Deep learning-based auto-segmentation (DLAS) has been used as a baseline for flagging manual segmentation errors, but those efforts are limited to using only one or two contour comparison metrics.

Purpose: The purpose of this research is to develop an improved contouring quality assurance system to identify and flag manual contouring errors.

Methods and materials: DLAS contours were used as a reference to compare with manually segmented contours. A total of 27 geometric agreement metrics were …

Single Center Retrospective Review Of Post-Laparotomy Ct Abdomen And Pelvis Findings And Trends, Dylan C. Steffey, Emad A. Chishti, Maximo J. Acevedo, Luis F. Acosta, James T. Lee

Radiology Faculty Publications

Purpose: To identify common findings visualized on CT following damage control laparotomy, including post-surgical changes and additional injuries, and to determine change in frequency of post-laparotomy CT at our institution over time.

Methods: Single institution, IRB-Exempt, retrospective review of the University of Kentucky trauma registry from 1/2006 to 2/2019 for all trauma patients undergoing exploratory laparotomy initially and subsequently undergoing CT of the abdomen and pelvis within 24 hours. Operative findings from surgical operation notes and findings reported on post-laparotomy CT were recorded, including vascular and solid organ injuries, operative changes, free intraperitoneal fluid/air, and retroperitoneal findings. Next steps in …

Combined Transhepatic And Transjugular Approach For Mechanical Thrombectomy Of Massive Tips Thrombosis, Jack B. Newcomer, Emad A. Chishti, Driss Raissi

Radiology Faculty Publications

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated decompressive therapy option to manage ascites and variceal bleeding secondary to portal hypertension. Complications following TIPS procedures include hepatic encephalopathy, liver failure, and TIPS dysfunction. TIPS dysfunction is due to occlusion or stenosis of the TIPS shunt and can be caused by acute or chronic thrombosis. TIPS thrombosis is often treated with mechanical thrombectomy or catheter-directed thrombolytic therapy. Most cases of in-stent occlusion can be treated via a transjugular approach with recanalization or placement of additional stents. We present a case of a 72-year-old female who presented with worsening ascites 17 months …

Aapm Medical Physics Practice Guideline 12.A: Fluoroscopy Dose Management, Ryan F. Fisher, Kimberly E. Applegate, Lindsey K. Berkowitz, Olav Christianson, Jaydev K. Dave, Lindsay Deweese, Nichole Harris, Mary Ellen Jafari, A. Kyle Jones, Robert J. Kobistek, Brendan Loughran, Loren Marous, Donald L. Miller, Beth Schueler, Bryan C. Schwarz, Adam Springer, Kevin A. Wunderle

Radiology Faculty Publications

No abstract provided.

Avoidable And Unavoidable Repeat Breast Core Needle Biopsies, Xiaoqin Wang, Fara Shikoh, Mauro Hanaoka, Aurela Clark

Radiology Faculty Publications

Background: Breast core needle biopsies are not perfect and could miss cancer. The need for a repeat breast core biopsy is not uncommon and can occur for a multitude of reasons. Radiologists should carefully correlate the pathology results with imaging features after each breast biopsy and must recognize why certain core biopsies must be repeated to avoid missed or delayed cancer diagnosis. In this review, we discuss the main reasons for repeat core biopsies via case presentation with radiological images and pathological correlation. This review will help multidisciplinary breast care team recognize when to repeat a biopsy to reduce false …

Blood Flow Restriction Training After Patellar Instability (Brains Trial), Benjamin D. Brightwell, Austin V. Stone, Xiaojuan Li, Peter A. Hardy, Katherine L. Thompson, Brian W. Noehren, Cale A. Jacobs

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background

Patellar instability is a common and understudied condition that disproportionally affects athletes and military personnel. The rate of post-traumatic osteoarthritis that develops following a patellar dislocation can be up to 50% of individuals 5–15 years after injury. Conservative treatment is the standard of care for patellar instability however, there are no evidence-informed rehabilitation guidelines in the scientific literature. The purpose of this study is to assess the effectiveness of blood-flow restriction training (BFRT) for patellar instability. Our hypotheses are that this strategy will improve patient-reported outcomes and accelerate restoration of symmetric strength and knee biomechanics necessary to safely return …

Short Chain Fatty Acids Taken At Time Of Thrombectomy In Acute Ischemic Stroke Patients Are Independent Of Stroke Severity But Associated With Inflammatory Markers And Worse Symptoms At Discharge, Nicholas Henry, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Andrew J. Morris, Jianzhong Chen, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks.

Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem …

Typical Sounding Atypical Diagnostic Conundrum -- A Rare Case Of Mycobacterium Avium Complex (Mac) Presenting With Multiple Cranial Nerve Involvement, Ashwini Kini, Karl Echiverri, Edward J. Escott, Padmaja Sudhakar

Neurology Faculty Publications

Background

MAC infections rarely cause symptomatic systemic infection in immunocompetent healthy individuals. This case brings to light a rare such presentation that gives us a learning point about keeping a strong pre-clinical suspicion for this condition in patients whom lung imaging reveals suspicious cavitary lesions. Starting empiric therapy while awaiting culture results may be considered after weighing risks and benefits in order to achieve the morbidity and mortality associated with the disease.

Case report

A 54 year-old white male presented for evaluation of progressively worsening vertigo, imbalance, vertical diplopia, facial diplegia, bilateral hyperacusis followed by hearing loss, dysphagia, and dysarthria …

Can Activated Titanium Interbody Cages Accelerate Or Enhance Spinal Fusion? A Review Of The Literature And A Design For Clinical Trials, Nathaniel Toop, Connor Gifford, Rouzbeh Motiei-Langroudi, Arghavan Farzadi, Daniel Boulter, Reza Forghani, H. Francis Farhadi

Neurosurgery Faculty Publications

While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale …

Bilateral Popliteal Entrapment Syndrome In A Young Athlete Diagnosed With Ultrasound, Hanna K. Thompson, Justin R. Montgomery, Paul J. Spicer

Radiology Faculty Publications

Popliteal artery entrapment syndrome (PAES) occurs when the popliteal artery is compressed by abnormally developed or hypertrophied muscles adjacent to the popliteal fossa. When symptomatic, it most frequently presents with leg cramping while walking or running. We describe the case of an 18-year-old female runner presenting with claudication and exercise intolerance. After MRI was non-diagnostic, diagnostic ultrasound demonstrated that she had functional (Type VI) PAES. She subsequently underwent popliteal artery release surgery. Type VI PAES should be considered in young, healthy patients who present with claudication, particularly athletes.

Multi-Vendor And Multisite Evaluation Of Cerebrovascular Reactivity Mapping Using Hypercapnia Challenge, Peiying Liu, Dengrong Jiang, Marilyn Albert, Christopher E. Bauer, Arvind Caprihan, Brian T. Gold, Steven M. Greenberg, Karl G. Helmer, Kay Jann, Gregory A. Jicha, Pavel Rodriguez, Claudia L Satizabal, Sudha Seshadri, Herpreet Singh, Jeffrey F. Thompson, Danny J. J. Wang, Hanzhang Lu

Neuroscience Faculty Publications

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate …

Cessation And Resumption Of Elective Neurointerventional Procedures During The Coronavirus Disease 2019 Pandemic And Future Pandemics, Tim W. Malisch, Sameer A. Ansari, Gary R. Duckwiler, Kyle M. Fargen, Steven W. Hetts, Franklin A. Marden, Athos Patsalides, Clemens M. Schirmer, Allan Brook, Justin F. Fraser

Neurosurgery Faculty Publications

At the time of this writing, the coronavirus disease 2019 pandemic continues to be a global threat, disrupting usual processes, and protocols for delivering health care around the globe. There have been significant regional and national differences in the scope and timing of these disruptions. Many hospitals were forced to temporarily halt elective neurointerventional procedures with the first wave of the pandemic in the spring of 2020, in order to prioritize allocation of resources for acutely ill patients and also to minimize coronavirus disease 2019 transmission risks to non-acute patients, their families, and health care workers. This temporary moratorium on …

Rapid 3d Reconstruction Guided Embolization For Catastrophic Bleeding Following Vacuum Assisted Breast Biopsy; A Case Report And Review Of The Literature, Martin Halicek, Chenghao Qian, Driss Raissi, Xiaoqin Wang, Yevgen Chornenkyy, William B. Bates, Michael Winkler

Radiology Faculty Publications

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization.

Intra-Arterial Combination Therapy For Experimental Acute Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Amanda A. Gorman, Gregory J. Bix, Justin F. Fraser

Neurosurgery Faculty Publications

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra-arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra-arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L-type calcium channels, whereas lubeluzole, …

Gamma Knife Radiosurgery To Four Brainstem Lesions After Whole Brain Radiation Therapy, Mark E. Bernard, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Our patient was a 58-year-old female with a history of extensive stage small cell lung cancer initially diagnosed in November 2018. She received palliative radiation to the right hip and whole brain in December of 2018 and then received chemotherapy. Unfortunately, in October 2019, the repeat brain magnetic resonance imaging (MRI) showed recurrent lesions and she was referred for Gamma Knife Radiosurgery (GKRS). At the time of the treatment, she was found to have four brainstem lesions as well as a left frontal lobe and a right frontal lobe lesion. She completed GKRS to all six lesions without any neurological …

Primary Bilateral Ovarian Artery Embolization For Uterine Leiomyomatosis In The Setting Of A Rare Anatomic Variant - Hypoplastic Uterine Arteries, Merve Ozen, Shezaan Momin, Charles Ben Myers, Mark Hoffman, Driss Raissi

Radiology Faculty Publications

We present the case of a 50-year-old female who underwent bilateral ovarian artery embolization for uterine fibroids in the setting of hypoplastic uterine arteries. Ovarian artery embolization is usually conducted during uterine artery embolization for fibroids to increase the procedure success when ovarian feeders are seen. The bilateral ovarian artery embolization is rarely performed due to fears of amenorrhea and early menopause from decreased blood supply to both ovaries. According to our knowledge, this the first case report describing primary bilateral ovarian artery embolization in the setting of a rare anatomic variant- hypoplastic uterine arteries. The patient had complete resolution …

Smoking-Induced Sex Differences In Clinical Outcomes In Patients Undergoing Mechanical Thrombectomy For Stroke, Jacqueline A. Frank, Kara Jo Swafford, Jill M. Roberts, Amanda L. Trout, Ann M. Stowe, Douglas E. Lukins, Stephen Grupke, Keith R. Pennypacker, Justin F. Fraser

Neurology Faculty Publications

OBJECTIVE: Ischemic stroke is the fifth leading cause of death in the United States. Smoking accelerates the onset of stroke by 10 years. The effects of smoking status on percent change in National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and edema volume were examined following mechanical thrombectomy for large vessel occlusion in patients with acute ischemic stroke.

METHODS: Subjects (N = 90; >18 years old) were divided into 3 groups based on smoking status: current smokers, previous smokers (defined as having quit >6 months before the ischemic event), and nonsmokers. Percent change in NIHSS score was …

Concurrent Covid-19 Infection In Children With Acute Appendicitis: A Report Of Three Cases, Maximo J. Acevedo, Dylan Steffey, Johanne E. Dillon, James T. Lee, David J. Worhunsky

Radiology Faculty Publications

Literature describing patients with concomitant COVID-19 infection with acute appendicitis in pediatric patients is growing, and understanding the clinical picture of such patients is relevant in their treatment. We report 3 male children who were surgically treated for acute appendicitis and had concomitant SARS-CoV-2 infection. Our first patient was a 12-year-old male who presented with symptoms indicative of appendicitis but no respiratory symptoms associated with COVID-19 (eg cough, shortness of breath). Laboratory evaluation revealed leukopenia and an elevated C-reactive protein; imaging was consistent with acute appendicitis and an acute pulmonary viral infection. Though he lacked diffuse peritonitis on physical examination …

Extrapulmonary Tuberculosis: A Case Report Involving The Spine And Soft Tissues, Aden Gunnar Miller, Paul J. Spicer

Radiology Faculty Publications

Tuberculosis (TB) is a major health concern worldwide, and its incidence is increasing in developed countries, especially among immigrant populations. Extrapulmonary TB with musculoskeletal involvement is often a difficult and delayed diagnosis, as the disease can mimic metastases or infection. We present a case of extrapulmonary TB affecting the spine and soft tissues of a Vietnamese-born patient living in the United States. We discuss the imaging findings associated with extrapulmonary TB of the spine. Familiarity with key imaging features of disease can lead to early suspicion and detection of the disease as well as timely treatment.

Operative Management Of Symptomatic, Metachronous Carotid Body Tumors Involving The Skull Base And Its Neurological Sequelae, Roberto G. Aru, Rony K. Aouad, Justin F. Fraser, Amanda M. Romesberg, Kevin W. Hatton, Sam C. Tyagi

Otolaryngology--Head & Neck Surgery Faculty Publications

A 44-year-old morbidly obese woman with a history of right carotid body tumor (CBT) resection presented with a symptomatic, nonfunctional, left Shamblin-III CBT. Abutment of the skull base precluded distal internal carotid artery control for arterial reconstruction, favoring parent vessel sacrifice after an asymptomatic provocative test. She underwent CBT resection with anticipated sacrifice of cranial nerves X and XII and the common carotid artery and its branches, developing baroreceptor failure syndrome and sequelae of cranial nerve sacrifice. When facing a symptomatic, metachronous CBT abutting the skull base, upfront operative intervention with adjuvant radiation for residual tumor optimizes curative resection.

Opioid And/Or Psychotropic Use Increases Intraprocedural Sedation Drug Requirements, Sreeja Sanampudi, Ravi Jayavarapu, Trae C. Brooks, Driss Raissi

Radiology Faculty Publications

Objectives Acute pain management in opioid users can be challenging in the perioperative period. This study focuses on whether use of opioids increases sedation medication requirements in patients undergoing port placement under moderate sedation.

Materials and Methods A retrospective review was performed on all patients undergoing port placement between June 1, 2017, and June 30, 2019. Exclusion criteria included receiving general anesthesia, no sedation, and errors in data entry. Data collection included demographics, use of opioids, benzodiazepines, antidepressants, tobacco, alcohol, and sedation data.

Results Opioid, benzodiazepine, and selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) use was significantly associated with …

Intracranial Vcam1 At Time Of Mechanical Thrombectomy Predicts Ischemic Stroke Severity, Benton Maglinger, Madison Sands, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Jill M. Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical …

Evaluation Of Glutaminase Expression In Prostate Adenocarcinoma And Correlation With Clinicopathologic Parameters, Zin W. Myint, Ramon C. Sun, Patrick J. Hensley, Andrew C. James, Peng Wang, Stephen E. Strup, Robert J. Mcdonald, Donglin Yan, William H. St. Clair, Derek B. Allison

Internal Medicine Faculty Publications

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, …

Recurrent Breast Cancer Diagnosis Delayed By Covid-19 Pandemic, Hannah K. Thompson, Paul J. Spicer

Radiology Faculty Publications

We describe the case of a 65-year-old female with a history of left-sided ductal carcinoma in situ in 2008. Mammography in January 2020 demonstrated calcifications in the previously affected breast. Subsequent stereotactic biopsy results were benign. In the months that followed, the patient experienced breast changes but avoided returning to the facility as the COVID-19 pandemic worsened. In August of 2020, the patient returned for a repeat mammogram, which indicated 2 suspicious masses in the left breast. Further analysis through ultrasound-guided core biopsy ultimately led to a left mastectomy and lymph node biopsy, which were performed in September 2020. Pathology …

Method Of Intra-Arterial Drug Administration In A Rat: Sex Based Optimization Of Infusion Rate, Sarah J. Messmer, Justin F. Fraser, Keith R. Pennypacker, Jill M. Roberts

Center for Advanced Translational Stroke Science Faculty Publications

BACKGROUND: Endovascular thrombectomy is the process of removing a blood clot and re-establishing blood flow in patients with emergent large vessel occlusion. The technique provides an opportunity to deliver therapeutics directly to the site of injury. The intra-arterial (IA) route of drug administration in the mouse was developed to bridge the gap between animal stroke treatments and clinical stroke therapy. Here, we adapted the IA method for use in rats, by investigating various flow rates to optimize the IA injection through the internal carotid artery (ICA).

METHODS: Male and female Sprague-Dawley rats (∼4 months of age) were subjected to placement …

Association Between Obesity And Histological Tumor Budding In Patients With Nonmetastatic Colon Cancer, Tong Gan, Kurt B. Schaberg, Daheng He, Akila Mansour, Harit Kapoor, Chi Wang, B. Mark Evers, Therese J. Bocklage

Surgery Faculty Publications

Importance: Obesity is associated with increased risk of colorectal cancer (CRC) and a more aggressive disease course. Tumor budding (TB) is an important prognostic factor for CRC, but its association with obesity is unknown.

Objective: To evaluate the association of TB with obesity and other prognostic factors in colon cancer.

Design, Setting, and Participants: This cohort study involved a histological review of colon cancer specimens obtained during 7 years (January 2008 to December 2015) at the University of Kentucky Medical Center; data analysis was conducted from February 2020 to January 2021. Specimens came from 200 patients with stage I to …

Radiopharmaceutical Validation For Clinical Use, Charles A. Kunos, Rodney Howells, Aman Chauhan, Zin W. Myint, Mark E. Bernard, Riham H. El Khouli, Jacek Capala

Internal Medicine Faculty Publications

Radiopharmaceuticals are reemerging as attractive anticancer agents, but there are no universally adopted guidelines or standardized procedures for evaluating agent validity before early-phase trial implementation. To validate a radiopharmaceutical, it is desirous for the radiopharmaceutical to be specific, selective, and deliverable against tumors of a given, molecularly defined cancer for which it is intended to treat. In this article, we discuss four levels of evidence—target antigen immunohistochemistry, in vitro and in vivo preclinical experiments, animal biodistribution and dosimetry studies, and first-in-human microdose biodistribution studies—that might be used to justify oncology therapeutic radiopharmaceuticals in a drug-development sequence involving early-phase trials. We …