First-in-Man Evaluation of 124I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment.

PURPOSE: PGN650 is a F(ab')2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. METHODS: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124I-PGN650 intravenously and underwent positron emission tomography-computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). RESULTS: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. CONCLUSION: Although 124I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies.

Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. IPF appears to be heterogeneous in pathobiology with ∼40% of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen (col(V)). Following a targeted, precision medicine approach, we conducted a phase 1 study to test the safety and explore potential efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody-positive IPF patients. We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period. All patients completed treatment without serious adverse events, acute exacerbations or IPF-related hospitalisations. A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials. In contrast, the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q to anti-col(V) antibodies. IW001 may modulate the immune response to col(V) and may represent a new therapeutic for col(V)- reactive IPF patients.

Narcotic Consumption Analysis among Severely Injured and Advanced Aged Trauma Patients.

BACKGROUND: Multimodal pain management has been shown to be effective in treating pain in acutely injured trauma patients. Our community-based, level 1 trauma center previously published in 2022 the efficacy of implementing multimodal pain control (MMPC) protocol in our inpatient trauma population which decreased the use of opioids while maintaining similar pain control. The MMPC group had a trend toward higher age and was significantly less injured. We hypothesize MMPC will reduce opioid consumption in both the advanced aged and more severely injured trauma populations while still providing adequate pain control. METHODS: Defined by the year of admission, MMPC and physician managed pain control (PMPC) were compared in both advanced age groups and between the severely injured groups. The advanced age group included patients ≥55 years old. The severely injured group included ≥18 years old with ≥15 ISS. Primary outcomes were total opioid utilization per day, calculated in morphine milliequivalents (MME), and median daily pain scores. RESULTS: For the severely injured population, the MMPC group showed a 3-fold decrease in opioid use (30 MME/d vs 90.3 MME/d, P < .001) and lower pain scores (5/10 vs 6/10, P < .001) than the PMPC group. In the advance age group, there was no significant difference between MMPC and PMPC groups in opioid use (P = .974) or pain scores (P = .553). CONCLUSION: MMPC effectively reduces opioid consumption in a severely injured patient population while simultaneously improving pain control. Advanced age trauma patients can require complex pain management solutions and future research to determine their needs is recommended.

SNMMI Clinical Trial Network Research Series for Technologists: Application of Good Clinical Practice to Clinical Research in Medical Imaging.

This article is part of a series developed by the Clinical Trials Network of the Society of Nuclear Medicine and Molecular Imaging to offer training and information for molecular imaging technologists and researchers about various aspects of clinical research. This article covers the topic of good clinical practice and how that relates to those portions of the Code of Federal Regulations that govern clinical research in the United States, such as title 21, part 312, and the Common Rule. The purpose of this article is to inform technologists and researchers about standard roles, documents, guidance, and processes that are elemental to the conduct of clinical trials and to offer additional resources for learning about these processes.

SNMMI Clinical Trials Network Research Series for Technologists: Clinical Research Primer-Regulatory Process, Part I: How and When Radiopharmaceuticals Can Be Used.

CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.The radiopharmaceutical development and approval process in the United States has changed dramatically over the past decade with the emergence of several new and exciting diagnostic and therapeutic drugs. This impressive expansion is a direct result of the symbiotic relationship that exists between drug development, clinical research, and improved regulatory guidance. The correlative increase in clinical research has introduced diverse opportunities for newcomers in medical and scientific professions. Knowing how to successfully navigate the clinical research process can be challenging for a novice. The pathway is highly regulated and, with the addition of radiopharmaceuticals, may be confusing and daunting. Moreover, very little clinical research education and training is provided in the typical collegiate curricula for these new initiates. This article will familiarize the reader with the U.S. regulatory process by providing basic definitions and understanding of how and when radiopharmaceuticals can be used in clinical research, including those involving investigational new drug applications and radioactive drug research committees. A later article will expand the reader's clinical research knowledge by focusing on the identity and role of the institutional review board.

Ancillary Finding on Myocardial Perfusion Imaging Due to Urinary Bladder Displacement.

When imaging patients are referred for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium 99m (99mTc) agents, the attention is focused on the tracer activity in the myocardium. Apart from myocardial activity, the normal biodistribution of 99mTc Sestamibi and 99mTc Tetrofosmin is seen in the thyroid, liver, gastrointestinal tract, kidneys, and urinary bladder. These structures may be visualized when a large field of view (FOV) gamma camera is used for SPECT imaging. This brief report presents a serendipitous finding of a pelvic mass, which was identified because of the extended field-of-view afforded by the conventional gamma camera used for SPECT MPI and detected because of a review of the raw images by the nuclear medicine technologist (NMT). This case emphasizes the importance of the NMT training to review the raw data in the entire FOV prior to study completion.

Multi-modal Pain Control Protocol Decreases Narcotic Consumption in an Inpatient Trauma Population.

INTRODUCTION: Opioid use after surgery or trauma has been implicated as a contributing factor to opioid dependence. The Acute Care Surgery (ACS) service at our community-based trauma center instituted an opioid-minimizing, multi-modal pain control (MMPC) protocol. The classes of pain medication included a non-opioid analgesic, a non-steroidal anti-inflammatory drug, a gabapentinoid, a skeletal muscle relaxant, and a topical anesthetic. We hypothesize that the MMPC will result in lower opioid consumption compared with the prior STP as evidenced by lower morphine milligram equivalents (MME) per day. METHODS: All adult patients (≥18 years) admitted to the ACS service from Jan 2014 to Dec 2015 and Jan 2018 to Dec 2019 were screened for inclusion. The standard pain control group (STP) and MMPC groups were defined by the year of admission. The primary outcome is opioid use per day, calculated in MME received. Secondary outcomes of the study include daily pain scores, incidence of opioid-related complications, death, ventilator days, intensive care unit length of stay, and hospital length of stay (HLOS) days. RESULTS: Multi-modal pain control protocol group was older and less injured than STP group. Daily opioid utilization was significantly less in the MMPC group (22.5 MMEs/d vs 60MMEs/d in the STP group, P < .0001). Additionally, daily pain scores were not different between groups. Secondary outcomes did not vary between the two groups. CONCLUSION: This study shows that implementation of a MMPC protocol resulted in lower opioid consumption in injured patients. Pain was equivalently controlled during the MMPC protocol period as demonstrated by similar pain scores.

SNMMI Clinical Trials Network Research Series for Technologists: Introduction.

The field of nuclear medicine and molecular imaging has grown tremendously over the past several years with the approval of new imaging agents, diagnostic radiopharmaceuticals, and radiopharmaceutical therapies. Clinical research continues to expand within nuclear medicine and molecular imaging departments. Working as a nuclear medicine technologist on a clinical trial or with investigational radiopharmaceuticals can be quite different from working in an approved-drug setting in the clinic. Nuclear medicine technologists involved in clinical trials can be at the front line of following rigorous trial requirements and ensuring good-quality data. The details of working in clinical research are often not taught in nuclear medicine technologist programs. As such, there is an emerging need for education about clinical research for both experienced and new nuclear medicine technologists, particularly for those working with investigational radiopharmaceuticals. This article is an introduction to the SNMMI Clinical Trials Network Research Series for Technologists. This series of articles aims to provide education on working in the context of a clinical trial within the nuclear medicine department. The following 7 topics will be addressed in the series: ethical issues in clinical research, application of good clinical practice to clinical research in medical imaging, contract research organizations with application in clinical imaging, a clinical research primer on the regulatory process for how and when radiopharmaceuticals can be used and the role of the institutional review board, use of imaging agents in therapeutic drug development and approval, imaging agent trials, and imaging agents with radiopharmaceutical therapies in clinical trials. Other topics may be added over the course of the development of the series.

SNMMI Clinical Trials Network Research Series for Technologists: Ethical Issues and Regulations in the Medical Workplace.

Ethical principles and laws have developed as medical practice and research have grown. This article discusses regulatory policies in patient care and the governing bodies that provide oversight. These include but are not limited to the Food and Drug Administration, Office for Human Research Protection, Code of Federal Regulations, Nuclear Regulatory Commission, Joint Commission, Health Insurance Portability and Accountability Act, Occupational Safety and Health Administration, World Health Organization, and International Conference on Harmonization. This article reviews ethical requirements in clinical research and provides examples of medical mistreatment that forced the development of these rules and regulations. Some include the Nuremberg Code, Declaration of Helsinki, and Belmont Report; good clinical practice; and the Common Rule. Several specific research documents are discussed further in this continuing education series. These guiding documents and principles are important because every patient and research subject deserves a safe environment with safe products and protection of privacy. Individuals deserve to understand their role in medicine and clinical research, have the right to refuse care, make informed decisions, know the risks and benefits included, and ultimately have their individual choices respected.

Monitoring Individual Occupational Radiation Exposure at Multiple Institutions.

Within a few years of its' discovery, ionizing radiation demonstrated adverse effects on biological systems. Since that time great strides were made in both radiation protection, detection, and personnel monitoring. Monitoring occupational radiation dose to individuals is enforced by several regulatory agencies in the United States (U.S.) and is referenced in numerous sections of the Code of Federal Regulations (CFR). A literature review with an examination of regulatory guidelines and a Radiation Safety Officers (RSO) survey was conducted to evaluate how often radiation dose exposure is monitored when an individual receives occupational radiation dose at more than one facility. The length of time an RSO has overseen the radiation safety program at his/her institution can impact if dosimetry reports are requested for individuals that work at multiple places. Despite having safer equipment and occupational radiation exposure standards, there is no universal mechanism to track and record exposure for individuals working at more than one institution.

Review of HIPAA, Part 2: Limitations, Rights, Violations, and Role for the Imaging Technologist.

This article is the second part of a continuing education series reviewing the Health Insurance Portability and Accountability Act (HIPAA) of 1996. The term HIPAA should be familiar to those who work in the medical profession, but this article includes details on its rules, patients' rights, violations, breaches, and penalties. To help administer these safeguards, HIPAA requires that every organization designate a HIPAA privacy and security officer. HIPAA violations can have serious repercussions when rules are not followed; these violations can be either negligent or willful. If breaches of unsecured protected health information occur, HIPAA requires covered entities to notify affected individuals, the Secretary of Health and Human Services, and in some cases the media. Violations in which the covered entity did not know of the violation are now punishable under the first tier of penalties. Unintended violations carry a minimum penalty of $100 per violation and a maximum of $50,000 per violation. All patients have a right to privacy and a right to confidential use of their medical records. The role of medical professionals includes understanding how and when to apply these HIPAA rules verbally and electronically.

Development of Simple Methods to Reduce the Exposure of the Public to Radiation from Patients Who Have Undergone 18F-FDG PET/CT.

At a time when reducing the radiation dose to patients and the public has become a major focus, we assessed the radiation exposure rate from patients after an 18F-FDG PET/CT scan and evaluated different interventions to reduce it. Methods: We enrolled 100 patients, divided into 2 groups. For both groups, the radiation dose rate was measured with an ionization survey meter immediately after the scan. For group 1, the patients then voided and their dose rate was measured again. For group 2, the patients waited 30 min before voiding, and we measured the dose rate before (group 2A) and after (group 2B) they voided. Results: In total, 74 of the 100 patients exceeded the 20 µSv/h (2 mR/h) threshold immediately after the scan. In group 1, the mean dose rate decreased by 20.0% from the postscan measurement, with 12 of 36 remaining at or above 20 µSv/h. In group 2A, the mean dose rate decreased by 23% from the postscan measurement, with 9 of 38 remaining at or above 20 µSv/h. In group 2B, the mean dose rate decreased by 35% from the postscan measurement, with 1 of 38 remaining at 20 µSv/h. Conclusion: Nearly 75% of patients undergoing an 18F-FDG PET/CT scan exceed 20 µSv/h when leaving the imaging facility. The most effective method to reduce radiation exposure was to have the patient void 30 min after the examination.

Added Value of Digital over Analog PET/CT: More Significant as Image Field of View and Body Mass Index Increase.

The digital PET/CT scanner with digital photon-counting technique promises a shorter scan time, improved small-lesion detectability, and reduced radiation dose for the PET and CT portions of the exam while improving image quality. Methods: In this single-institution retrospective review study, 84 participants who had undergone PET/CT on both analog and digital scanners were analyzed. The aim was to evaluate the impact of image field of view (FOV) and body mass index (BMI) on the digital compared with the analog PET/CT scanners. The participants were categorized into different groups based on their BMI. Total scan times, 18F-FDG doses, and dose-length products (DLP) were collected and compared. Image quality was also assessed by certified nuclear medicine physicians and graded on a scale from 1 to 5. Results: In the skull-to-mid-thigh FOVs, the digital scanner had a scan time shorter by 37% (P < 0.001), a 18F-FDG dose lower by 16% (P < 0.001), but only an 8% reduction in DLP (P = 0.2). In the head-to-toe FOV cases, the digital scanner showed reductions in scan time (33%; P < 0.001), 18F-FDG dose (13%; P < 0.001), and DLP (19%; P < 0.001). When BMI was accounted for, the digital scanner had a scan time shorter by 33% (P < 0.001), as well as a reduced DLP (P < 0.001) and 18F-FDG dose (P < 0.001), with the most prominent changes being in the overweight and obese participants. Image quality was also improved by the digital scanner, with a score of 4.5, versus 4.0 for the analog scanner. Conclusion: The digital scanner has a shorter scan time and lower DLP, requires a lower 18F-FDG dose, and provides improved image quality when compared with the analog scanner. The most impactful difference in scan time, DLP, and 18F-FDG dose were observed in obese and overweight participants.

Treatment With Oral Versus Intravenous Acetaminophen in Elderly Trauma Patients With Rib Fractures: A Prospective Randomized Trial.

BACKGROUND: Rib fractures are common injuries among traumatically injured patients, and elderly patients with rib fractures are at increased risk for adverse events and death. The purpose of this study was to determine if oral Per os (PO) acetaminophen is as effective as intravenous (IV) acetaminophen in treating the pain associated with rib fractures. METHODS: We performed a single-center, randomized, placebo-controlled, double-blinded study. Trauma patients who were ≥65 years old and had ≥1 rib fracture were included in this study. Patients were randomized into IV acetaminophen and oral placebo (n = 63) or IV placebo and oral solution acetaminophen (n = 75) groups. The primary outcome was a mean reduction in pain score at 24 hours, and secondary outcomes included opioid use, intensive care unit (ICU) length of stay (LOS), hospital LOS, hospital mortality, the difference in incentive spirometry, and development of pneumonia. RESULTS: Among the 138 patients included, there was no statistically significant difference between the 2 study groups in a mean reduction in pain score at 24 hours after injury (PO: 3.24, IV: 2.49; P = .230). Opioid pain medication use was equivalent between groups (P = .212), and there was no significant difference in hospital mortality rate between groups (P = .827). There was no statistically significant difference in ICU LOS, hospital LOS, or development of pneumonia. DISCUSSION: In elderly trauma patients (age ≥65 years) with 1 or more rib fractures, PO acetaminophen is equivalent to IV acetaminophen for pain control, with no difference in morbidity or mortality. Oral acetaminophen should be preferentially used over IV acetaminophen when treating the elderly trauma patient with rib fractures.

Review of HIPAA, Part 1: History, Protected Health Information, and Privacy and Security Rules.

The Health Insurance Portability and Accountability Act (HIPAA) of 1996 has made an impact on the operation of health-care organizations. HIPAA includes 5 titles, and its regulations are complex. Many are familiar with the HIPAA aspects that address protection of the privacy and security of patients' medical records. There are new rules to HIPAA that address the implementation of electronic medical records. HIPAA provides rules for protected health information (PHI) and what should be protected and secured. The privacy rule regulates the use and disclosure of PHI and sets standards that an entity working with health data must follow to protect patients' private medical information. The HIPAA security rule complements the privacy rule and requires entities to implement physical, technical, and administrative safeguards to protect the privacy of PHI. This article-part 1 of a 2-part series-is a refresher on HIPAA, its history, its rules, its implications, and the role that imaging professionals play.

The Need for Increased Awareness About Potential Quality Control Problems in Aging γ-Cameras.

Quality control in a nuclear medicine department plays an important role in providing quality care for patients. Closely monitoring the uniformity values on extrinsic quality control can give insight into problems outside typical equipment issues. This facility noticed increasing uniformity values along with a photopenic image artifact. The detector required photocoupling gel replacement and a full rebuild by service engineers. This process required time for the rebuild and time for the gel to set. Another adjustment of the voltage to the photomultiplier tubes (PMTs) was required due to photocathode excitation in every cathode in every PMT in that detector. After the detector was rebuilt, the voltage was retuned with the field service engineers' knowledge that the PMTs would need to be retuned due to this excitation. Communication and understanding of equipment problems in aging γ-cameras can lead to proper equipment use and better quality in nuclear medicine departments.

Association Between Altered Hip Extension and Kinetic Gait Variables.

Kinematic and kinetic outcome measures are tightly linked in walking. Although altering motor output is a major goal of gait rehabilitation, little is understood regarding the relationship between altering a single kinematic variable and kinetic outcome changes. We designed a strategy to isolate hip extension alterations during walking on a treadmill to assess the change in kinetic outcomes. Ten healthy individuals walked on an instrumented split-belt treadmill with motion capture to calculate hip extension and kinetic outcomes at the following five different randomized cadences: self-selected cadence, self-selected ± 10%, and self-selected ± 20%. The treadmill speed was held constant at the individual's self-selected walking speed, forcing cadence changes to result in successful alterations to hip extension, varying 8.3 degrees from the self-selected -20% to +20% cadence conditions. Kinetic outcomes demonstrated similar alterations. Hip extension changes at each cadence significantly correlated with kinetic changes in propulsive impulse (r = 0.852, P < 0.001), peak ankle power (r = 0.473, P = 0.002), and ankle plantarflexion work (r = 0.762, P < 0.001). These results demonstrate that kinetic outcomes are highly alterable in response to a kinematic gait change. This clinically relevant finding highlights the potential to improve motor output in individuals during rehabilitation by altering gait patterns to achieve more optimal limb positions.

Usefulness of Topically Applied Sensors to Assess the Quality of 18F-FDG Injections and Validation Against Dynamic Positron Emission Tomography (PET) Images.

Background: Infiltrations of 18F-fluorodeoxyglucose (FDG) injections affect positron emission tomography/computed tomography (PET/CT) image quality and quantification. A device using scintillation sensors (Lucerno Dynamics, Cary, NC) provides dynamic measurements acquired during FDG uptake to identify and characterize radioactivity near the injection site prior to patient imaging. Our aim was to compare sensor measurements against dynamic PET image acquisition, our proposed reference in assessing injection quality during the uptake period. Methods: Subjects undergoing routine FDG PET/CT imaging were eligible for this Institutional Review Board approved prospective study. After providing informed consent, subjects had sensors topically placed on their arms. FDG was injected into subjects' veins directly on the PET imaging table. Dynamic images of the injection site were acquired during 45 min of the uptake period. These dynamic image acquisitions and subjects' routine standard static images were evaluated by nuclear medicine physicians for abnormal FDG accumulation near the injection site. Sensor measurements were interpreted independently by Lucerno staff. Dynamic image acquisition interpretation results were compared to the sensor measurement interpretations and to static image interpretations. Results: Twenty-four subjects were consented and enrolled. Data from 21 subjects were gathered. During dynamic image acquisition review, physicians interpreted 4 subjects with no FDG accumulation at the injection site, whereas 17 showed evidence of accumulation. In 10 of the 17 cases that showed FDG accumulation, the FDG presence at the injection site resolved completely during uptake corresponding to venous stasis, the temporary sequestration of blood from circulation. Static image interpretation agreed with dynamic images interpretation in 11/21 (52%) subjects. Sensor measurement interpretations agreed with the dynamic images interpretations in 18/21 (86%) subjects. Conclusions: Sensor measurements can be an effective way to identify and characterize infiltrations and venous stasis. Comparable to an infiltration, venous stasis may produce spurious and clinically meaningful measurement bias and possibly even scan misinterpretation. Since the quality and quantification of PET/CT studies are of clinical importance, sensor measurements acquired during the FDG uptake may prove to be a useful quality control measure to reduce infiltration rates and potentially improve patient care. Registration: Clinicaltrials.gov, Identifier: NCT03041090.

Correction: Type V Collagen Induced Tolerance Suppresses Collagen Deposition, TGF-ß and Associated Transcripts in Pulmonary Fibrosis.

[This corrects the article DOI: 10.1371/journal.pone.0076451.].

Novel Method to Detect and Characterize 18F-FDG Infiltration at the Injection Site: A Single-Institution Experience.

A novel quality control and quality assurance device provides time-activity curves that can identify and characterize PET/CT radiotracer infiltration at the injection site during the uptake phase. The purpose of this study was to compare rates of infiltration detected by the device with rates detected by physicians. We also assessed the value of using the device to improve injection results in our center. Methods: 109 subjects consented to the study. All had passive device sensors applied to their skin near the injection site and mirrored on the contralateral arm during the entire uptake period. Nuclear medicine physicians reviewed standard images for the presence of dose infiltration. Sensor-generated time-activity curves were independently examined and then compared with the physician reports. Injection data captured by the software were analyzed, and the results were provided to the technologists. Improvement measures were implemented, and rates were remeasured. Results: Physician review of the initial 40 head-to-toe field-of-view images identified 15 cases (38%) of dose infiltration (9 minor, 5 moderate, and 1 significant). Sensor time-activity curves on these 40 cases independently identified 22 cases (55%) of dose infiltration (16 minor, 5 moderate, and 1 significant). After the time-activity curve results and the contributing factor analysis were shared with technologists, injection techniques were modified and an additional 69 cases were studied. Of these, physician review identified 17 cases (25%) of infiltration (13 minor, 3 moderate, and 1 significant), a 34% decline. Sensor time-activity curves identified 4 cases (6%) of infiltration (2 minor and 2 moderate), an 89% decline. Conclusion: The device provides valuable quality control information for each subject. Time-activity curves can further characterize visible infiltration. Even when the injection site was out of the field of view, the time-activity curves could still detect and characterize infiltration. Our initial experience showed that the quality assurance information obtained from the device helped reduce the rate and severity of infiltration. The device revealed site-specific contributing factors that helped nuclear medicine physicians and technologists customize their quality improvement efforts to these site-specific issues. Reducing infiltration can improve image quality and SUV quantification, as well as the ability to minimize variability in a site's PET/CT results.