Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

PSMA Radioligand Therapy in Prostate Cancer: Where Are We and Where Are We Heading?

ABSTRACT: Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific membrane antigen agents has been proven beneficial in certain clinical indications. In this review, we describe management of prostate cancer patients according to current guidelines, especially focusing on the available clinical evidence for prostate-specific membrane antigen radioligand therapy.

Skeletal Fluorosis.

ABSTRACT: A 27-year-old man with polysubstance abuse including methamphetamine, fentanyl, and 1.5 years of electronics compressed gas duster inhalation presented following an assault. Radiologic imaging performed for suspected fractures revealed periosteal reaction, cortical thickening with increased bone density, and ligament and tendon ossification, which were not present on imaging obtained 3 years before presentation. A bone scan was subsequently performed revealing a metabolic superscan with cortical irregularity. Further investigation revealed skeletal fluorosis from electronics compressed gas duster inhalation. Skeletal fluorosis may be considered when these osseous findings are encountered.

Clinical Trials of Prostate-Specific Membrane Antigen Radiopharmaceutical Therapy.

Prostate-specific membrane antigen (PSMA) theranostics has been a momentous triumph for nuclear medicine. The recent approvals of PSMA-targeted imaging agents (68Ga-PSMA-11, 18F-DCFPyL) and radiopharmaceutical therapy (177Lu-PSMA-617) have paved the way for theranostics as a viable care strategy for men with metastatic castration-resistant prostate cancer. The imaging clinical trials OSPREY, CONDOR, and those conducted at the University of California (Los Angeles and San Francisco), as well as the randomized phase 3 therapy trial VISION, have been the fruitful beginnings for PSMA theranostics. There are currently several ongoing clinical trials to expand the reach of PSMA theranostics to the earlier phases of prostate cancer and to optimize its utility in combination therapeutic regimens. We provide a brief narrative review of the many PSMA-directed radiopharmaceutical therapy clinical trials with the ß-emitter 177Lu-PSMA-617 and the α-emitter 225Ac-PSMA-617 in prostate cancer.

Re: Aducanumab-Related ARIA: Paean or Lament?

ABSTRACT: Høilund-Carlsen and colleagues raise concern regarding the reliability of amyloid PET to exclude Alzheimer disease. We present additional studies of amyloid PET and discuss the diagnostic challenges in Alzheimer disease. We discuss the limitations of amyloid in diagnosis and evaluation of therapy response in AD.

Supply Issues in Nuclear Medicine.

ABSTRACT: Issues related to the distribution and availability of supplies and personnel in nuclear medicine are well known and episodic. The combination of COVID-related restrictions and the unprecedented growth of our specialty have acutely exacerbated these supply and demand mismatches.

Molecular Imaging Assessment of Androgen Deprivation Therapy in Prostate Cancer.

Hormonal therapy has long been recognized as a mainstay treatment for prostate cancer. New generation imaging agents have provided unprecedented opportunities at all phases along the natural history of prostate cancer. We review the literature on the effect of androgens and androgen deprivation therapy on prostate tumor at its various biological phases using the new generation molecular imaging agents in conjunction with positron emission tomography.

Commentary: Aducanumab-Related ARIA: Paean or Lament?

ABSTRACT: Høilund-Carlsen and colleagues raise important issues related to amyloid PET, diagnosis of Alzheimer disease, and recently approved antiamyloid treatment aducanumab. We discuss new developments that may direct us to methods of presymptomatic detection of Alzheimer disease and development of effective prevention and therapy.

Sentinel Node Biopsy Imaging in Breast Cancer: Scatter Reduction Using 3-Dimensionally Printed Lead Shields.

BACKGROUND: Point of injection scatter (SPI) confounds breast cancer sentinel lymph node detection. Round flat lead shields (FLSs) incompletely reduce SPI, requiring repositioning. We designed lead shields that reduce SPI and acquisition time. METHODS: Two concave lead shields, a semioval lead shield (OLS) and a semispherical lead alloy shield (SLS), were created with a SICNOVA JCR 1000 3D printer to cover the point of injection (patent no. ES1219895U). Twenty breast cancer patients had anterior and anterior oblique imaging, 5 minutes and 2 hours after a single 111 MBq nanocolloid in 0.2 mL intratumoral or periareolar injection. Each acquisition was 2 minutes. Absolute and normalized background corrected scatter counts (CSCs) and scatter reduction percentage (%SR) related to the FLS were calculated. Repositionings were recorded. Differences between means of %SR (t test) and between means of CSC (analysis of variance) with Holm multiple comparison tests were determined. RESULTS: Mean %SR was 91.8% with OLS and 92% using SLS in early images (P = 0.91) and 87.2%SR in OLS and 88.5% in late images (P = 0.66). There were significant differences between CSC using FLS and OLS (P < 0.001) and between FLS and SLS (P < 0.001), but not between OLS and SLS (P = 0.17) in early images, with the same results observed in delayed studies (P < 0.001 in relation to FLS and P = 0.1 between both curved lead shields). Repositioning was required 14/20 times with FLS, 4/20 times with OLS, and 2/20 times with SLS. CONCLUSIONS: We designed 2 concave lead shields that significantly reduce the SPI and repositioning with sentinel lymph node lymphoscintigraphy.

EANM guideline on the role of 2-[18F]FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA).

In most patients with ovarian carcinoma, the diagnosis is reached when the disease is long past the initial stages, presenting already an advanced stage, and they usually have a very bad prognosis. Cytoreductive or debulking surgical procedures, platinum-based chemotherapy and targeted agents are key therapeutic elements. However, around 7 out of 10 patients present recurrent disease within 36 months from the initial diagnosis. The metastatic spread in ovarian cancer follows three pathways: contiguous dissemination across the peritoneum, dissemination through the lymphatic drainage and, although less importantly in this case, through the bloodstream. Radiological imaging, including ultrasound, CT and MRI, are the main imaging techniques in which management decisions are supported, CT being considered the best available technique for presurgical evaluation and staging purposes. Regarding 2-[18F]FDG PET/CT, the evidence available in the literature demonstrates efficacy in primary detection, disease staging and establishing the prognosis and especially for relapse detection. There is limited evidence when considering the evaluation of therapeutic response. This guideline summarizes the level of evidence and grade of recommendation for the clinical indications of 2-[18F]FDG PET/CT in each disease stage of ovarian carcinoma.

Hip Adduction during Running: Influence of Sex, Hip Abductor Strength and Activation, and Pelvis and Femur Morphology.

PURPOSE: To examine the influence of hip abductor strength, neuromuscular activation, and pelvis and femur morphology in contributing to sex differences in hip adduction during running. In addition, we sought to determine the best predictors of hip adduction during running for both men and women. METHODS: Fifteen female runners and 14 male runners underwent strength testing, instrumented overground running (e.g., kinematics and muscle activation), and computed tomography scanning of pelvis and femur. Morphologic measurements included bilateral hip width to femur length ratio, acetabulum abduction, acetabulum anteversion, femoral anteversion, and femoral neck-shaft angles. Sex differences for all variables were examined using independent t tests. Linear regression was used to assess the ability of each independent variable of interest to predict peak hip adduction during the late swing and stance phase of running. RESULTS: Compared with men, women exhibited significantly greater peak hip adduction during both late swing (8.5° ± 2.6° vs 6.2° ± 2.8°, P = 0.04) and stance phases of running (13.4° ± 4.2° vs 10.0° ± 3.2°, P = 0.02). In addition, women exhibited significantly lower hip abductor strength (1.8 ± 0.3 vs 2.0 ± 0.3 N·m·kg-1, P = 0.04), greater femoral neck-shaft angles (134.1° ± 5.0° vs 129.9° ± 4.1°, P = 0.01), and greater hip width to femur length ratios than men (0.44 ± 0.02 vs 0.42 ± 0.03, P = 0.03). Femoral anteversion was the only significant predictor of peak hip adduction during late swing (r = 0.36, P = 0.05) and stance (r = 0.41, P = 0.03). CONCLUSIONS: Our findings highlight the contribution of femur morphology as opposed to hip abductor strength and activation in contributing to hip adduction during running.

ACR Appropriateness Criteria® Intensive Care Unit Patients.

Chest radiography is the most frequent and primary imaging modality in the intensive care unit (ICU), given its portability, rapid image acquisition, and availability of immediate information on the bedside preview. Due to the severity of underlying disease and frequent need of placement of monitoring devices, ICU patients are very likely to develop complications related to underlying disease process and interventions. Portable chest radiography in the ICU is an essential tool to monitor the disease process and the complications from interventions; however, it is subject to overuse especially in stable patients. Restricting the use of chest radiographs in the ICU to only when indicated has not been shown to cause harm. The emerging role of bedside point-of-care lung ultrasound performed by the clinicians is noted in the recent literature. The bedside lung ultrasound appears promising but needs cautious evaluation in the future to determine its role in ICU patients. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Targeted α-therapy in non-prostate malignancies.

Progress in unraveling the complex biology of cancer, novel developments in radiochemistry, and availability of relevant α-emitters for targeted therapy have provided innovative approaches to precision cancer management. The approval of 223Ra dichloride for treatment of men with osseous metastatic castrate-resistant prostate cancer unleashed targeted α-therapy as a safe and effective cancer management strategy. While there is currently active research on new α-therapy regimens for prostate cancer based on the prostate-specific membrane antigen, there is emerging development of radiopharmaceutical therapy with a range of biological targets and α-emitting radioisotopes for malignancies other than the prostate cancer. This article provides a brief review of preclinical and first-in-human studies of targeted α-therapy in the cancers of brain, breast, lung, gastrointestinal, pancreas, ovary, and the urinary bladder. The data on leukemia, melanoma, myeloma, and neuroendocrine tumors will also be presented. It is anticipated that with further research the emerging role of targeted α-therapy in cancer management will be defined and validated.

Agreement Between 18F-FDG PET/CT and Whole-Body Magnetic Resonance Compared With Skeletal Survey for Initial Staging and Response at End-of-Treatment Evaluation of Patients With Multiple Myeloma.

PURPOSE: To compare the agreement between whole-body (WB) magnetic resonance (MR) imaging, 18F-FDG PET/CT, and skeletal survey (SS) in patients with multiple myeloma (MM) for diagnosis, initial staging, response evaluation, and early detection of complications. METHODS: This is a retrospective cohort study including MM patients who were diagnosed, treated, and followed in 2 institutions. These patients were studied with SS, WB-MR, and/or 18F-FDG PET/CT. We studied bone lesions by anatomical locations and analyzed the concordance between SS and a tomographic technique (WB-MR or 18F-FDG PET/CT) and between both tomographic techniques (WB-MR and PET/CT). RESULTS: Forty-four MM patients with a mean age of 62.6 years (range, 38-85 years) were included from January 2012 to February 2016. Whole-body MR and 18F-FDG PET/CT found more lesions than SS in every location except in the skull. Concordance between WB-MR and 18F-FDG PET/CT was either good or excellent in most of the locations and in plasmacytoma studies. However, WB-MR was better than 18F-FDG PET/CT in the study of complications (medullar compression and vascular necrosis). CONCLUSIONS: Our results suggest the study of MM patients should include WB-MR and/or 18F-FDG PET/CT, whereas SS is only useful for the skull. Whole-body MR and 18F-FDG PET/CT are complementary techniques, because both of them show good concordance in almost every location. It is still necessary to individualize the indication of each technique according to patient characteristics.

Machine learning-based differentiation between multiple sclerosis and glioma WHO II°-IV° using O-(2-[18F] fluoroethyl)-L-tyrosine positron emission tomography.

INTRODUCTION: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°. METHODS: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance. RESULTS: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm. CONCLUSIONS: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.

Novel Experience in Hybrid Tracers: Clinical Evaluation of Feasibility and Efficacy in Using ICG-99mTc Nanotop for Sentinel Node Procedure in Breast Cancer Patients.

PURPOSE: The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. METHODS: The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. RESULTS: Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed. CONCLUSIONS: The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.

Venous Air Embolism Identified by 18F-Fluorocholine Dual-Phase PET/CT.

ABSTRACT: A 60-year-old woman with primary hyperparathyroidism with previous nonconclusive imaging studies was referred for 18F-fluorocholine (18F-FCH) PET/CT as part of the preoperative diagnostic imaging workup to localize the adenoma before minimally invasive surgery. 18F-FCH PET/CT with dual time point was performed, acquiring immediately and 60 minutes after 18F-FCH administration. The early images demonstrated possible hyperfunctioning parathyroid tissue in the mediastinum, located in the right upper paratracheal space (region 2R), with an incidental iatrogenic subclavian venous air bubble embolism presenting as high uptake in the early images that disappeared in the late images. No symptomatology was reported during the examination.

ACR Appropriateness Criteria® Blunt Chest Trauma-Suspected Cardiac Injury.

Blunt cardiac injuries range from myocardial concussion (commotio cordis) leading to fatal ventricular arrhythmias to myocardial contusion, cardiac chamber rupture, septal rupture, pericardial rupture, and valvular injuries. Blunt injuries account for one-fourth of the traumatic deaths in the United States. Chest radiography, transthoracic echocardiography, CT chest with and without contrast, and CT angiography are usually appropriate as the initial examination in patients with suspected blunt cardiac injury who are both hemodynamically stable and unstable. Transesophageal echocardiography and CT heart may be appropriate as examination in patients with suspected blunt cardiac injuries. This publication of blunt chest trauma-suspected cardiac injuries summarizes the literature and makes recommendations for imaging based on the available data and expert opinion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.