Essentials of Theranostics: A Guide for Physicians and Medical Physicists.

Radiopharmaceutical therapies (RPTs) are gaining increased interest with the recent emergence of novel safe and effective theranostic agents, improving outcomes for thousands of patients. The term theranostics refers to the use of diagnostic and therapeutic agents that share the same molecular target; a major step toward precision medicine, especially for oncologic applications. The authors dissect the fundamentals of theranostics in nuclear medicine. First, they explain the radioactive decay schemes and the characteristics of emitted electromagnetic radiation used for imaging, as well as particles used for therapeutic purposes, followed by the interaction of the different types of radiation with tissue. These concepts directly apply to clinical RPTs and play a major role in the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that can help estimate patient-specific absorbed doses, in tumors as well as normal organs. Dosimetry in RPT is an area of active investigation, as most of what we know about the relationship between delivered dose and tissue damage is extrapolated from external-beam radiation therapy; more research is needed to understand this relationship as it pertains to RPTs. Tumor heterogeneity is increasingly recognized as an important prognostic factor. Novel molecular imaging agents, often in combination with fluorine 18-fluorodeoxyglucose, are crucial for assessment of target expression in the tumor and potential hypermetabolic disease that may lack the molecular target expression. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Current Applications of PET/MR: Part II: Clinical Applications II.

Due to the major improvements in the hardware and image reconstruction algorithms, positron emission tomography/magnetic resonance imaging (PET/MR) is now a reliable state-of-the-art hybrid modality in medical practice. Currently, it can provide a broad range of advantages in preclinical and clinical imaging compared to single-modality imaging. In the second part of this review, we discussed the further clinical applications of PET/MR. In the chest, PET/MR has particular potential in the oncology setting, especially when utilizing ultrashort/zero echo time MR sequences. Furthermore, cardiac PET/MR can provide reliable information in evaluating myocardial inflammation, cardiac amyloidosis, myocardial perfusion, myocardial viability, atherosclerotic plaque, and cardiac masses. In gastrointestinal and hepato-pancreato-biliary malignancies, PET/MR is able to precisely detect metastases to the liver, being superior over the other imaging modalities. In genitourinary and gynaecology applications, PET/MR is a comprehensive diagnostic method, especially in prostate, endometrial, and cervical cancers. Its simultaneous acquisition has been shown to outperform other imaging techniques for the detection of pelvic nodal metastases and is also a reliable modality in radiation planning. Lastly, in haematologic malignancies, PET/MR can significantly enhance lymphoma diagnosis, particularly in detecting extra-nodal involvement. It can also comprehensively assess treatment-induced changes. Furthermore, PET/MR may soon become a routine in multiple myeloma management, being a one-stop shop for evaluating bone, bone marrow, and soft tissues.

Theranostics in Neuroendocrine Tumors.

ABSTRACT: Neuroendocrine tumors (NETs) are rare tumors that develop from cells of the neuroendocrine system and can originate in multiple organs and tissues such as the bowels, pancreas, adrenal glands, ganglia, thyroid, and lungs. This review will focus on gastroenteropancreatic NETs (more commonly called NETs) characterized by frequent somatostatin receptor (SSTR) overexpression and pheochromocytomas/paragangliomas (PPGLs), which typically overexpress norepinephrine transporter. Advancements in SSTR-targeted imaging and treatment have revolutionized the management of patients with NETs. This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration-approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.

Night and Day, Why Radiologists Need Play.

What is play and why does it matter for radiologists? Play can take many forms in the workplace, including organic, managed, task-related, diversionary, and resistive forms of play, and play may also take the form of authentic self-expression and creation. In this review article, we will discuss the benefits of play including improved problem solving, gaining perspective, and stress reduction, and also provide low-tech and high-tech examples of beneficial play for the radiology team in work and personal contexts.

Theranostics in Neuroendocrine Tumors: Updates and Emerging Technologies.

Advancements in somatostatin receptor (SSTR) targeted imaging and treatment of well-differentiated neuroendocrine tumors (NETs) have revolutionized the management of these tumors. This comprehensive review delves into the current practice, discussing the use of the various FDA-approved SSTR-agonist PET tracers and the predictive imaging biomarkers, and elaborating on Lu177-DOTATATE peptide receptor radionuclide therapy (PRRT) including the evolving areas of post-therapy imaging practices, PRRT retreatment, and the potential role of dosimetry in optimizing patient treatments. The future directions sections highlight ongoing research on investigational PET imaging radiotracers, future prospects in alpha particle therapy, and combination therapy strategies.

Use of PSMA PET/CT to detect prostate cancer metastatic to a preexisting thyroid nodule.

Prostate cancer (PCa) seldom metastasizes to the thyroid gland, and only a limited number of cases are documented in the literature. The application of a relatively recent and highly sensitive imaging technique, prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT), has enhanced the identification of metastatic disease. Nevertheless, as PSMA is expressed in various tissue types, the clinical importance of a PSMA-avid thyroid lesion remains largely uncertain. A minor, yet noteworthy, percentage of these lesions are ultimately determined to be malignant. Here we describe the case of a 70-year-old man with a past medical history of Lynch syndrome who presented to an outpatient oncologic clinic for management of very high risk localized PCa. He developed metastatic recurrence and his disease progressed through several lines of therapy, including immunotherapy and targeted treatments. He was found to have a new, intense PSMA uptake in an existing, previously benign thyroid nodule. Sonographic evaluation revealed changing morphology despite grossly stable size. Repeat biopsy confirmed the unusual finding of PCa metastasis to a known thyroid nodule. The shift in PSMA avidity played a pivotal role in discerning this metastatic deposit. There is a potential risk that such lesions may be inadequately acknowledged. The impact of the patient's Lynch syndrome on this presentation remains uncertain.

PET/MRI: pictorial review of hepatobiliary and pancreatic applications.

PET and MRI both play valuable roles in the management of hepatobiliary and pancreatic (HBP) malignancies. Simultaneous PET/MRI combines the excellent soft-tissue resolution and anatomic details from MRI with functional information from PET in a single comprehensive examination. MRI is the main imaging modality in evaluating HCC, playing important roles in screening, characterization, local extent, and evaluating tumor response, whereas 18F-fluorodeoxyglucose (FDG) PET can help evaluate for lymph node involvement and metastatic disease. In cholangiocarcinoma and pancreatic malignancies, both PET and MRI have excellent utility in initial staging as well as assessing treatment response. In all HBP malignancies, FDG-PET/MRI is a unique problem-solving tool in complex cases and diagnostic challenges, especially after locoregional therapy and when differentiating residual or recurrent viable disease from inflammatory and other benign processes. In this manuscript, we review the role of PET/MRI in the diagnosis, staging, assessing treatment response, and characterizing post-treatment processes. With the introduction of multiple new tracers, the value of PET/MRI has not yet been fully realized, and more studies are needed to demonstrate the utility and efficacy of PET/MRI in improving patient care in hepatobiliary and pancreatic oncology.

Imaging of the hepatic arterial infusion pump: Primer for radiologists.

Hepatic arterial infusion (HAI) pumps are used to deliver liver-directed therapy by allowing the administration of selective chemotherapy to the liver via a catheter implanted most commonly into the gastroduodenal artery connected to a subcutaneous pump. This selective administration helps maximize the chemotherapeutic effect within the hepatic tumors while minimizing systemic toxicity. While HAI therapy has primarily been used to treat liver-only metastatic colorectal cancer, the indications have expanded to other malignancies, including intrahepatic cholangiocarcinoma. Radiologists play an important role in pre-operative planning, assessment of treatment response, and evaluation for potential complications using various imaging studies, including computed tomography angiography, magnetic resonance imaging, and perfusion scintigraphy. This article describes the radiologist's role as part of a multi-disciplinary oncology team to help maximize the success of HAI therapy and also helps radiologists familiarize themselves with various aspects of HAI pumps.

Quantitative imaging for 177Lu-PSMA treatment response monitoring and dosimetry.

PSMA-targeted radiopharmaceutical therapy is an established treatment option for metastatic castration-resistant prostate cancer (mCRPC). However, response rates and duration using 177Lu-PSMA-617 vary considerably between patients. Quantitative 177Lu SPECT imaging is one approach that may be leveraged to more closely monitor inter-cycle response, as well as patient-specific absorbed doses. In this work, we describe our experience implementing quantitative imaging throughout the course of 177Lu-PSMA treatment, including serial SPECT imaging to monitor response and for individualized dosimetry. We also describe our imaging protocols and dose calculation workflows for 3D voxelized patient-specific organ and tumor dosimetry, including a review of the current landscape and efforts towards harmonized dosimetry.

Monitoring and Surveillance of Patients with Gastroenteropancreatic Neuroendocrine Tumors Undergoing Radioligand Therapy.

Radioligand therapy (RLT) with [177Lu]Lu-DOTA-TATE is a standard of care for adult patients with somatostatin-receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Taking advantage of this precision nuclear medicine approach requires diligent monitoring and surveillance, from the use of diagnostic SSTR-targeted radioligand imaging for the selection of patients through treatment and assessments of response. Published evidence-based guidelines assist the multidisciplinary healthcare team by providing acceptable approaches to care; however, the sheer heterogeneity of GEP-NETs can make these frameworks difficult to apply in individual clinical circumstances. There are also contradictions in the literature regarding the utility of novel approaches in monitoring and surveilling patients with GEP-NETs receiving RLT. This article discusses the emerging evidence on imaging, clinical biochemistry, and tumor assessment criteria in the management of patients receiving RLT for GEP-NETs; additionally, it documents our own best practices. This allows us to offer practical guidance on how to effectively implement monitoring and surveillance measures to aid patient-tailored clinical decision-making.

Molecular and Anatomic Imaging of Neuroendocrine Tumors.

Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we review the role of SSTR PET scan in the management of NETs, including the indications for the scan, pitfalls in interpretation, and imaging selection criteria for peptide receptor radionuclide therapy. We also discuss the complementary role of fluorodeoxyglucose PET particularly for patients with high-grade disease.

[18F]-fluoromisonidazole (FMISO) PET/MRI hypoxic fraction distinguishes neuroinflammatory pseudoprogression from recurrent glioblastoma in patients treated with pembrolizumab.

Response assessment after immunotherapy remains a major challenge in glioblastoma due to an expected increased incidence of pseudoprogression. Gadolinium-enhanced magnetic resonance imaging (MRI) is the standard for monitoring therapeutic response, however, is markedly limited in characterizing pseudoprogression. Given that hypoxia is an important defining feature of glioblastoma regrowth, we hypothesized that [18F]-fluoromisonidazole (FMISO) positron emission tomography (PET) could provide an additional physiological measure for the diagnosis of immunotherapeutic failure. Six patients with newly diagnosed glioblastoma who had previously received maximal safe resection followed by Stupp protocol CRT concurrent with pembrolizumab immunotherapy were recruited for FMISO PET and Gd-MRI at the time of presumed progression. The hypoxic fraction was defined as the ratio of hypoxic volume to T1-weighted gadolinium-enhancing volume. Four patients diagnosed with pseudoprogression demonstrated a mean hypoxic fraction of 9.8 ±â€…10%. Two with recurrent tumor demonstrated a mean hypoxic fraction of 131 ±â€…66%. Our results, supported by histopathology, suggest that the noninvasive assessment of hypoxic fraction by FMISO PET/MRI is clinically feasible and may serve as a biologically specific metric of therapeutic failure.

Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of malignancies originating from neuroendocrine cells of the gastrointestinal tract, the incidence of which has been increasing for several decades. While there has been significant progress in the development of therapeutic options for patients with advanced or metastatic disease, these remain limited both in quantity and durability of benefit. This review examines the latest research elucidating the mechanisms of both up-front resistance and the eventual development of resistance to the primary systemic therapeutic options including somatostatin analogues, peptide receptor radionuclide therapy with lutetium Lu 177 dotatate, everolimus, sunitinib, and temozolomide-based chemotherapy. Further, potential strategies for overcoming these mechanisms of resistance are reviewed in addition to a comprehensive review of ongoing and planned clinical trials addressing this important challenge.

Somatostatin Receptor Imaging and Theranostics: Current Practice and Future Prospects.

A new era of precision diagnostics and therapy for patients with neuroendocrine neoplasms began with the approval of somatostatin receptor (SSTR) radiopharmaceuticals for PET imaging followed by peptide receptor radionuclide therapy (PRRT). With the transition from SSTR-based γ-scintigraphy to PET, the higher sensitivity of the latter raised questions regarding the direct application of the planar scintigraphy-based Krenning score for PRRT eligibility. Also, to date, the role of SSTR PET in response assessment and predicting outcome remains under evaluation. In this comprehensive review article, we discuss the current role of SSTR PET in all aspects of neuroendocrine neoplasms, including its relation to conventional imaging, selection of patients for PRRT, and the current understanding of SSTR PET-based response assessment. We also provide a standardized reporting template for SSTR PET with a brief discussion.

Clinical Utility of Pretreatment and 3-Month 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Standardized Uptake Value in Predicting and Assessing Recurrence in T3-T4 Laryngeal Carcinoma Treated With Definitive Radiation.

OBJECTIVES: The aim of this study was to investigate the utility of pretreatment and 3-month 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) standardized uptake value (SUV) in predicting and assessing recurrence in T3-T4 laryngeal carcinoma treated with definitive radiation therapy (RT). METHODS: Patients with newly diagnosed T3-T4 laryngeal squamous cell carcinoma treated with definitive RT from 2004 to 2014 were reviewed. Patients who underwent pretreatment or 3-month PET/CT 2 to 4 months after treatment were included. Those with prior systemic, surgical, or RT treatment were excluded. The primary objective was to assess whether pretreatment or posttreatment maximum SUV of the primary site (pSUV) of disease was associated with local recurrence-free survival. Overall survival was a secondary end point. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the accuracy of 3-month PET/CT at the larynx primary. RESULTS: Twenty-eight patients were eligible for analysis. Median follow-up time was 34.7 months (range, 5.3-138.7 months), and median age was 57 years. Most patients had supraglottic (71.4%), T3 (89.3%), N2 (50.0%) disease, received chemotherapy (96.4%), and had histories of tobacco use (96.4%). On univariate analysis, 3-month posttreatment pSUV was associated with local recurrence-free survival ( P < .01), while pretreatment pSUV was not ( P = .41). No other associations were found with local recurrence-free survival. Neither pretreatment nor 3-month pSUV was significantly associated with overall survival. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of 3-month PET/CT at the primary site were 33%, 85%, 40%, and 81%, respectively. CONCLUSIONS: High initial fluorodeoxyglucose uptake in T3-T4 laryngeal primaries did not show an association with the risk for postradiation local relapse or overall survival, while increased fluorodeoxyglucose uptake at 3 months was associated with increased local recurrence. At 3 months, the relatively low sensitivity and positive predictive value may limit the utility of PET/CT in the assessment of persistent advanced laryngeal cancer after definitive radiation.

PET/MR Imaging of the Pancreas.

PET/MR imaging has the potential to markedly alter pancreatic care in both the malignant, and premalignant states with the ability to perform robust, high-resolution, quantitative molecular imaging. The ability of PET/MR imaging to monitor disease processes, potentially correct for motion in the upper abdomen, and provide novel biomarkers that may be a combination of MR imaging and PET biomarkers, offers a unique, precise interrogation of the pancreatic milieu going forward.

Morbidity and mortality of thyroidectomy for substernal goiter.

BACKGROUND: Our objective was to evaluate morbidity and mortality of thyroidectomy in substernal goiters and identify patients at risk for these events. METHODS: The medical records of 127 patients with substernal goiters were retrospectively reviewed. RESULTS: The most common preoperative symptom was shortness of breath (48%). 13% of the 127 patients were asymptomatic. Preoperative imaging identified tracheal deviation in 69% and tracheal compression in 41% of the cases. Substernal goiters were resected via a cervical approach in 100% of the cases. Six patients (5%) had postoperative hoarseness, 1 had permanent vocal cord paralysis, and 19 (15%) had transient postoperative hypocalcemia. The mortality and permanent hypoparathyroidism were null. Patients with postoperative complications had larger goiters and were more likely to have tracheal compression. CONCLUSIONS: Thyroid resection via a cervical approach for substernal goiters is associated with low rate of morbidity and no mortality. Patients with large tumors and tracheal compression are more likely to develop postoperative complications.