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.

Abbreviated Breast MRI for Supplemental Screening in Patients With Dense Breasts: Comparison of Baseline Versus Subsequent-Round Examinations.

Background: Abbreviated breast MRI (AB-MR) achieves a higher cancer detection rate (CDR) versus digital breast tomosynthesis when applied for baseline (i.e. first-round) supplemental screening in individuals with dense breasts. Limited literature has evaluated subsequent (i.e., sequential) AB-MR screening rounds. Objectives: This study aimed to compare outcomes between baseline and subsequent rounds of screening AB-MR in individuals with dense breasts at otherwise average risk of breast cancer. Methods: This retrospective study included patients with dense breasts and at otherwise average breast-cancer risk who underwent AB-MR for supplemental screening between December 20, 2016 and May 10, 2023. Clinical interpretations and results of recommended biopsies for AB-MR examinations were extracted from the EMR. Baseline and subsequent-round AB-MR examinations were compared. Results: The final sample included 2585 AB-MR examinations (2007 baseline, 578 subsequent-round) performed for supplemental screening in 2007 women (mean age, 57.1 years) with dense breasts. Among baseline examinations, 1658 (82.6%) were assessed as BI-RADS category 1 or 2, 171 (8.5%) as category 3, and 178 (8.9%) as category 4 or 5. Among subsequent-round examinations, 533 (92.2%) were assessed as BI-RADS category 1 or 2, 20 (3.5%) as category 3, and 25 (4.3%) as category 4 or 5 (p<.001). Abnormal interpretation rate (AIR) was 17.4% (349/2007) among baseline examinations, versus 7.8% (45/578) among subsequent-round examinations (p<.001). Among baseline examinations, PPV2 was 21.3% (38/178), PPV3 was 26.6% (38/143), and CDR was 18.9 per 1000 (38/2007). Among subsequent-round examinations PPV2 was 28.0% (7/25) (p=.45), PPV3 was 29.2% (7/24) (p=.81), and CDR was 12.1 per 1000 (7/578) (p=.37). All 45 cancers diagnosed by baseline or subsequent-round AB-MR were stage 0 or 1. Seven cancers diagnosed by subsequent-round AB-MR had a mean interval since prior AB-MR of 872 days, size of 0.3-1.2 cm, and node-negative status at surgical axillary evaluation. Conclusion: Subsequent rounds of AB-MR screening in individuals with dense breasts had lower AIR compared to baseline examinations while maintaining high CDR. All cancers detected by subsequent-round examinations were early-stage node-negative cancers. Clinical Impact: The findings support sequential AB-MR for supplemental screening in individuals with dense breasts. Further investigations are warranted to optimize the screening interval.

Molecular Imaging of Steroid Receptors in Breast Cancer.

ABSTRACT: Steroid receptors regulate gene expression for many important physiologic functions and pathologic processes. Receptors for estrogen, progesterone, and androgen have been extensively studied in breast cancer, and their expression provides prognostic information as well as targets for therapy. Noninvasive imaging utilizing positron emission tomography and radiolabeled ligands targeting these receptors can provide valuable insight into predicting treatment efficacy, staging whole-body disease burden, and identifying heterogeneity in receptor expression across different metastatic sites. This review provides an overview of steroid receptor imaging with a focus on breast cancer and radioligands for estrogen, progesterone, and androgen receptors.

PET Imaging of Metabolism, Perfusion, and Hypoxia: FDG and Beyond.

ABSTRACT: Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and guide targeted treatment.

Maximizing Mentorship Throughout Your Breast Imaging Career.

Unlike many other subspecialties in radiology, breast radiologists practice in a patient-facing and interdisciplinary environment where team building, communication, and leadership skills are critical. Although breast radiologists can improve these skills over time, strong mentorship can accelerate this process, leading to a more successful and satisfying career. In addition to providing advice, insight, feedback, and encouragement to mentees, mentors help advance the field of breast radiology by contributing to the development of the next generation of leaders. During the mentorship process, mentors continue to hone their listening, problem-solving, and networking skills, which in turn creates a more supportive and nurturing work environment for the entire breast care team. This article reviews important mentorship skills that are essential for all breast radiologists. Although some of the principles apply to all mentoring relationships, ensuring that every breast radiologist has the skills to be both an effective mentor and mentee is key to the future of the profession.

Fluorine-18-Labeled Fluoroestradiol PET/CT: Current Status, Gaps in Knowledge, and Controversies-AJR Expert Panel Narrative Review.

PET/CT using 16α-[18F]-fluoro-17ß-estradiol (FES) noninvasively images tissues expressing estrogen receptors (ERs). FES has undergone extensive clinicopathologic validation for ER+ breast cancer and received FDA approval in 2020 for clinical use as an adjunct to biopsy in patients with recurrent or metastatic ER+ breast cancer. Clinical use of FES PET/CT is increasing, but is not widespread in the United States. This AJR Expert Panel Narrative Review explores the present status and future directions of FES PET/CT, including image interpretation, existing and emerging uses, knowledge gaps, and current controversies. Specific controversies discussed include whether both FES PET/CT and FDG PET/CT are warranted in certain scenarios, whether further workup is required after negative FES PET/CT results, whether FES PET/CT findings should inform endocrine therapy selection, and whether immunohistochemistry should remain the standalone reference standard for determining ER status for all breast cancers. Consensus opinions from the panel include agreement with the appropriate clinical uses of FES PET/CT published by a multidisciplinary expert workgroup in 2023; anticipated expanded clinical use of FES PET/CT for staging ER-positive invasive lobular carcinomas and low-grade invasive ductal carcinomas pending ongoing clinical trial results; and the need for further research regarding use of FES PET/CT for ER-expressing nonbreast malignancies.

PSMA Uptake in a Subdural Hematoma.

ABSTRACT: An 81-year-old man with known metastatic prostate cancer with recent biochemical progression underwent a PSMA PET/CT ( 18 F-piflufolastat) for restaging. Review of the images demonstrated an acute or chronic left cerebral convexity subdural hematoma on CT with corresponding radiotracer activity throughout the collection on PET. Analysis of the patient's prior imaging showed that this subdural hematoma had significantly increased in size when compared with a head CT obtained 2 months prior. The patient was referred to a nearby emergency department and underwent repeat imaging and subdural drain placement. Unfortunately, the patient died secondary to rapid reaccumulation of subdural blood products after intervention.

Metabolic Positron Emission Tomography in Breast Cancer.

Metabolic PET, most commonly 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT), has had a major impact on the imaging of breast cancer and can have important clinical applications in appropriate patients. While limited for screening, FDG PET/CT outperforms conventional imaging in locally advanced breast cancer. FDG PET/CT is more sensitive than conventional imaging in assessing treatment response, accurately predicting complete response or nonresponse in early-stage cases. It also aids in determining disease extent and treatment response in the metastatic setting. Further research, including randomized controlled trials with FDG and other metabolic agents such as fluciclovine, is needed for optimal breast cancer imaging.

Other Novel PET Radiotracers for Breast Cancer.

Many novel PET radiotracers have demonstrated potential use in breast cancer. Although not currently approved for clinical use in the breast cancer population, these innovative imaging agents may one day play a role in the diagnosis, staging, management, and even treatment of breast cancer.

Male Breast Imaging Uncovers Lymphoma.

Background: A 36-year-old man presented with a palpable mass in the right axillary tail for four months. He was referred to breast imaging for diagnostic work-up. He does not have a family history of breast cancer. Aim: Breast imaging work-up for diagnosis of lymphoma is unusual and even more so in a male patient. Case presentation: After Breast Mammography and targeted Ultrasound of the axillary tail and axilla, Magnetic Resonance Imaging (MRI) was performed and suggested lymphoproliferative disorder. Excisional biopsy was performed after the breast MRI with removal of right axillary tissue measuring 15.0 × 5.5 × 2.0 cm and containing multiple lymph nodes. Excisional biopsy revealed Classic Hodgkin lymphoma of nodular sclerosis type. Staging [18F]-FDG PET/CT revealed early stage of disease. Conclusion: The presentation and diagnostic elements of Hodgkin Lymphoma are described in this case report emphasizing the significance of breast imaging in multiple populations.

18F-Fluoroestradiol: Current Applications and Future Directions.

In the United States, breast cancer is the second leading cause of cancer death in all women and the leading cause of cancer death in Black women. The breast cancer receptor profile, assessed with immunohistochemical staining of tissue samples, allows prediction of outcomes and direction of patient treatment. Approximately 80% of newly diagnosed breast cancers are hormone receptor (HR) positive, which is defined as estrogen receptor (ER) and/or progesterone receptor (PR) positive. Patients with ER-positive disease can be treated with therapies targeting the ER; however, the assessment of ER expression with immunohistochemical staining of biopsy specimens has several limitations including sampling error, false-negative results, challenging or inaccessible biopsy sites, and the inability to synchronously and serially assess all metastatic sites to identify spatial and/or temporal ER heterogeneity. In May 2020, after decades of research, the U.S. Food and Drug Administration approved the PET radiotracer fluorine 18 (18F) fluoroestradiol (FES) for clinical use in patients with ER-positive recurrent or metastatic breast cancer as an adjunct to biopsy. FES binds to the ER in the nucleus of ER-expressing cells, enabling whole-body in vivo assessment of ER expression. This article is focused on the approved uses of FES in the United States, including identification of a target lesion for confirmatory biopsy, in vivo assessment of biopsy-proven ER-positive disease, and evaluation of spatial and temporal ER heterogeneity. FES is an example of precision medicine that has been leveraged to optimize the care of patients with breast cancer. © RSNA, 2023 See the invited commentary by Fowler in this issue. Quiz questions for this article are available through the Online Learning Center.

Mammographic Breast Density: Current Assessment Methods, Clinical Implications, and Future Directions.

Mammographic breast density is widely accepted as an independent risk factor for the development of breast cancer. In addition, because dense breast tissue may mask breast malignancies, breast density is inversely related to the sensitivity of screening mammography. Given the risks associated with breast density, as well as ongoing efforts to stratify individual risk and personalize breast cancer screening and prevention, numerous studies have sought to better understand the factors that impact breast density, and to develop and implement reproducible, quantitative methods to assess mammographic density. Breast density assessments have been incorporated into risk assessment models to improve risk stratification. Recently, novel techniques for analyzing mammographic parenchymal complexity, or texture, have been explored as potential means of refining mammographic tissue-based risk assessment beyond breast density.

Widespread micronodular hepatic metastases of neuroendocrine tumor detected by [68Ga]DOTATATE PET/CT.

Neuroendocrine tumors (NET) encompass a diverse, heterogeneous group of neoplasms that originate from the secretory cells of the neuroendocrine system. These neoplasms typically express the somatostatin receptor (SSTR), which can be targeted by molecular agents for imaging and therapy. This is particularly advantageous for imaging NETs that are indolent, slow-growing, and less well detected by [18F]FDG and for the detection of occult disease not easily identified by anatomic imaging. Herein, we present a case in which [68Ga]DOTATATE PET/CT was used to diagnose the etiology of biochemical recurrence in NET that was not apparent on MRI. The importance of understanding deviations from the normal biodistribution of the radiotracer is emphasized as key in interpreting nuclear medicine studies and establishing the diagnosis. Imaging the SSTR is of particular interest given the recent FDA approval of [68Cu]DOTATATE as a new and possibly more available molecular radiotracer.

Prediction of 177Lu-DOTATATE Therapy Outcomes in Neuroendocrine Tumor Patients Using Semi-Automatic Tumor Delineation on 68Ga-DOTATATE PET/CT.

BACKGROUND: Treatment of metastatic neuroendocrine tumors (NET) with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) results in favorable response only in a subset of patients. We investigated the prognostic value of quantitative pre-treatment semi-automatic 68Ga-DOTATATE PET/CT analysis in NET patients treated with PRRT. METHODS: The medical records of 94 NET patients who received at least one cycle of PRRT at a single institution were retrospectively reviewed. On each pre-treatment 68Ga-DOTATATE PET/CT, the total tumor volume (TTV), maximum tumor standardized uptake value for the patient (SUVmax), and average uptake in the lesion with the lowest radiotracer uptake (SUVmin) were determined with a semi-automatic tumor delineation method. Progression-free survival (PFS) and overall survival (OS) among the patients were compared based on optimal cutoff values for the imaging parameters. RESULTS: On Kaplan-Meier analysis and univariate Cox regression, significantly shorter PFS was observed in patients with lower SUVmax, lower SUVmin, and higher TTV. On multivariate Cox regression, lower SUVmin and higher TTV remained predictive of shorter PFS. Only higher TTV was found to be predictive of shorter OS on Kaplan-Meier and Cox regression analyses. In a post hoc Kaplan-Meier analysis, patients with at least one high-risk feature (low SUVmin or high TTV) showed shorter PFS and OS, which may be the most convenient parameter to measure in clinical practice. CONCLUSIONS: The tumor volume and lowest lesion uptake on 68Ga-DOTATATE PET/CT can predict disease progression following PRRT in NET patients, with the former also predictive of overall survival. NET patients at risk for poor outcomes following PRRT can be identified with semi-automated quantitative analysis of 68Ga-DOTATATE PET/CT.

Novel applications of molecular imaging to guide breast cancer therapy.

The goals of precision oncology are to provide targeted drug therapy based on each individual's specific tumor biology, and to enable the prediction and early assessment of treatment response to allow treatment modification when necessary. Thus, precision oncology aims to maximize treatment success while minimizing the side effects of inadequate or suboptimal therapies. Molecular imaging, through noninvasive assessment of clinically relevant tumor biomarkers across the entire disease burden, has the potential to revolutionize clinical oncology, including breast oncology. In this article, we review breast cancer positron emission tomography (PET) imaging biomarkers for providing early response assessment and predicting treatment outcomes. For 2-18fluoro-2-deoxy-D-glucose (FDG), a marker of cellular glucose metabolism that is well established for staging multiple types of malignancies including breast cancer, we highlight novel applications for early response assessment. We then review current and future applications of novel PET biomarkers for imaging the steroid receptors, including the estrogen and progesterone receptors, the HER2 receptor, cellular proliferation, and amino acid metabolism.

Introduction to Radiopharmaceutical Therapy.

Radiopharmaceutical therapy (RPT) is a precision medicine modality in which administered radionuclides are preferentially taken up by target cells or nearby tissues and emit radiation from within the patient, leading to targeted cell death. Many radiopharmaceuticals are currently FDA-approved with multiple others under investigation. This manuscript will give a broad introduction to RPT including how to become an authorized user, patient evaluation pre- and post-treatment, dosing strategies, and the physical spaces needed to run an RPT clinic. RPT may seem daunting at first but is feasible. As approved radiopharmaceuticals and RPT uses increase, patients will benefit from greater access to these new and evolving treatment options.