Responsible Radionuclide Cancer Care.

The landscape of nuclear oncology is rapidly changing. The advent of molecular radionuclide theranostics, multidisciplinary tumor board decision making, artificial intelligence and radiomics interpretation of diagnostic imaging, evolution of pharmacogenomics prediction of tumor response, and regulatory requirements for prospective individual dosimetry are just some of the elements which are broadening the essence of physician responsibility. The burgeoning knowledge base essential for mastering the emergent technologies, and their profound effect on moral philosophic aspects of provision of cancer care, are challenging. The new relationship of the theranostic nuclear physician with respect to shared care of the individual patient, particularly with regard to transparency, accountability, and responsibility for targeted radionuclide diagnosis and therapy of cancer, will be explored in this update.

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into the cellular and molecular mechanisms underlying these variable responses will bring us closer to developing more effective therapeutics. To assess these mechanisms, non-invasive imaging techniques provide valuable whole-body information with precise targeting. An example of such is immuno-PET (Positron Emission Tomography), which employs radiolabeled antibodies to detect specific molecules of interest. Nanobodies, as the smallest derived antibody fragments, boast ideal characteristics for this purpose and have thus been used extensively in preclinical models and, more recently, in clinical early-stage studies as well. Their merit stems from their high affinity and specificity towards a target, among other factors. Furthermore, their small size (~14 kDa) allows them to easily disperse through the bloodstream and reach tissues in a reliable and uniform manner. In this review, we will discuss the powerful imaging potential of nanobodies, primarily through the lens of imaging malignant tumors but also touching upon their capability to image a broader variety of nonmalignant diseases.

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta-analysis.

AIMS: The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis. METHODS AND RESULTS: MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias. CONCLUSIONS: Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.

Theranostics in neuroendocrine tumours: somatostatin receptor imaging and therapy.

Theranostics and its principles: pre-treatment selection of patients who are most likely to benefit from treatment by the use of a related, specific diagnostic test are integral to the treatment of patients with neuroendocrine tumours (NETs). This is due to NETs' important, but variable, somatostatin receptor (SSTR) expression, their heterogeneity and variation in site of primary and rate of progression. Only patients whose tumours have sufficient expression of SSTRs will benefit from SSTR-based radionuclide therapy and demonstrating this expression prior to therapy is essential. This article provides a relevant overview of NETs and the multiple facets of SSTR based theranostics, including imaging and therapy radionuclides; clinical efficacy and toxicity; patient selection and treatment and finally emerging radiopharmaceuticals and newer clinical applications.

Will 68Ga PSMA-radioligands be the only choice for nuclear medicine in prostate cancer in the near future? A clinical update. / ¿Constituirán en el futuro los radioligandos de 68Ga-PSMA la única elección de la Medicina Nuclear para el cáncer de próstata? Actualización clínica.

Prostate Cancer (PCa) represents the most common malignant tumor in men but according to the European Association of Urology (EAU) guidelines, a mass screening for PCa diagnosis should not be performed due to over-diagnosis and over-treatment related problems. An early clinical diagnosis is possible, mainly based on digital rectal examination and Prostatic Specific Agent (PSA) testing. However, the only mandatory test to define the presence of PCa is ultrasound guided-biopsy, obtained on multiple samples, which has also a high prognostic value. In this context, diagnostic imaging plays an important role as confirmed by EAU that in a 2016 update of their guidelines on PCa stated the importance of Positron Emission Tomography (PET) with 11C- or 18F-choline combined with computed tomography (CT) to identify local relapse, lymph node involvement and metastatic spread at all stages. Consequently, in 2017, the European Association of Nuclear Medicine (EANM) together with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) published new guidelines for 68Ga-Prostate Specific Membrane Antigen (PSMA) PET/CT to help physicians in the recommendation, execution and interpretation of PET/CT scans in patients with PCa. Thus, the aim of this 'evidence paper' is to define the current diagnostic algorithm in PCa in order to increase the general level of confidence in approaching such a crucial topic.

Preoperative Cardiac Stress Testing in the Southern California Vascular Outcomes Improvement Collaborative.

BACKGROUND: The objective of this study was to examine the use of preoperative cardiac stress testing (PCST) in the Southern California Vascular Outcomes Improvement Collaborative (So Cal VOICe). METHODS: A retrospective review was performed on data in all modules of the So Cal VOICe from September 2012 through May 2016. PCST was defined as stress echocardiogram or nuclear stress test. A new postoperative myocardial infarction (MI) was defined as troponin elevation and/or electrocardiogram/imaging changes with or without ischemic symptoms. Only elective cases in patients with asymptomatic cardiac status were included in the study. RESULTS: During the study period, 3,063 procedures meeting the inclusion criteria were performed in 7 registries: carotid endarterectomy (CEA), carotid artery stent, thoracic endovascular aneurysm repair, infrainguinal bypass (Infra), endovascular aneurysm repair (EVAR), suprainguinal bypass (Supra), and open abdominal aortic aneurysm repair (OAAA). PCST varied across registries from 17% in PVI to 62% in OAAA. PCST in CEA varied across 9 institutions from 10% to 79%. PCST in EVAR varied across 7 institutions from 14% to 83%. PCST in Infra varied across 4 institutions from 10% to 57%. Of the 12 patients across all registries who had a new MI, 6 had PCST, one of which was abnormal. CONCLUSIONS: The incidence of PCST varies widely across registries and institutions in the So Cal VOICe. Despite the wide variation, the incidence of new postoperative MI is exceptionally low. Further studies should evaluate the cost-effectiveness of the PCST practices and future quality improvement efforts should focus on standardization of indications for PCST.

Differentiating between benign and malignant thyroid nodules: An evidence-based approach in general practice

BACKGROUND: The widespread use of imaging techniques has led to more frequent detection of thyroid nodules, and while the majority are benign, the risk of malignancy in an adult ranges from 7% to 15%. General practitioners (GPs) must be able to evaluate thyroid nodules and refer cases when appropriate. OBJECTIVES: The aim of this article is to bring GPs up to date on the evidence-based management of thyroid nodules, with specific focus on neoplastic nodules, while highlighting significant changes in the 2015 American Thyroid Association guidelines. DISCUSSION: Thyroid nodules frequently occur in the general population. Differentiating between a benign and malignant nodule can be challenging, and community guidelines have standardised investigation, management and follow-up procedures. The key tests for risk stratification of thyroid nodules include serum thyroid-stimulating hormone testing, ultrasonography and fine-needle aspiration. GPs should be aware of the latest evidence-based recommendations for the appropriate management of a thyroid nodule.

Highlights lecture EANM 2015: the search for nuclear medicine's superheroes.

The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1).

Radionuclide imaging and treatment of thyroid cancer.

Over the past decades, the diagnostic methods and therapeutic tools for thyroid cancer (TC) have been greatly improved. In addition to the classical method of ingestion of radioactive iodine-131 (I131) and subsequent I123 and I124 positron emission tomography (PET) in therapy and examination, I124 PET-based 3-dimensional imaging, Ga68-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTANOC) PET/computed tomography (CT), Tc99m tetrofosmin, pre-targeted radioimmunotherapy, and peptide receptor radionuclide therapy have all been used clinically. These novel methods are useful in diagnosis and therapy of TC, but also have unavoidable adverse effects. In this review, we will discuss the development of nuclear medicine in TC examination and treatment.

Radiopeptides for Imaging and Therapy: A Radiant Future.

Radiopeptides are powerful tools for diagnostic imaging and radionuclide therapy of various diseases. Since the introduction of the first radiopeptide into the clinical setting to diagnose neuroendocrine tumors about 25 y ago, many advances have been made in the field. This short review highlights novel strategies to improve the application of radiopeptides for imaging and therapy.

GLP-1 and exendin-4 for imaging endocrine pancreas. A review. Labelled glucagon-like peptide-1 analogues: past, present and future.

Glucagon-like peptide 1 (GLP-1) receptors expression has been found on many types of cancer cells. In case of benign insulinoma the density of those receptors is even higher than the density of somatostatin receptors. This article presents the results of clinical trials proving the utility of GLP-1 receptors imaging. Scintigraphy or positron emission tomography with the use of GLP-1 analogues labelled with appropriate radioisotopes (111In, 99mTc, 68Ga, 18F or 64Cu) seem to be superior compared with other available techniques in diagnosis of hardly detectable benign insulinoma. While surgery is the only effective therapy for insulinoma patients, therefore proper preoperative localization of the tumor allows sparing operation. Glucagon-like peptide 1 receptors might become also a target for imaging of other tumors such as gastrinoma, pheochromocytoma and medullary thyroid cancer (MTC), which also were shown to overexpress this type of receptors. However, studies with larger groups of patients are required to prove the clinical usefulness of this indication. Moreover GLP-1 receptor imaging seems to be a potential tool to evaluate pancreatic beta cell mass (BCM). It may be useful in the early diagnosis of beta cell loss in preclinical phases of diabetes. The panceratic beta cells imaging may influence the prophylaxis of diabetes and management of diabetic patients. Presented results of clinical trials prove that glucagon-like peptide 1 receptor imaging might become helpful diagnostic strategy particularly in case of patients with benign insulinoma tumors, but also patients with gastrinoma, pheochromocytoma, medullary thyroid cancer and diabetes.

GEP-NETS update: functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs).

For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a multidisciplinary team of skilled health care professionals. In these patients, a combination of nuclear medicine imaging and conventional radiological imaging techniques is usually mandatory for primary tumour visualisation, tumour staging and evaluation of treatment. In specific cases, as in patients with occult insulinomas, sampling procedures can provide a clue as to where to localise the insulin-hypersecreting pancreatic NETs. Recent developments in these fields have led to an increase in the detection rate of primary GEP-NETs and their metastatic deposits. Radiopharmaceuticals targeted at specific tumour cell properties and processes can be used to provide sensitive and specific whole-body imaging. Functional imaging also allows for patient selection for receptor-based therapies and prediction of the efficacy of such therapies. Positron emission tomography/computed tomography (CT) and single-photon emission CT/CT are used to map functional images with anatomical localisations. As a result, tumour imaging and tumour follow-up strategies can be optimised for every individual GEP-NET patient. In some cases, functional imaging might give indications with regard to future tumour behaviour and prognosis.

Patient demographics, quality of life, and disease features of men with newly diagnosed prostate cancer: trends in the PSA era.

OBJECTIVE: To describe how demographic and diagnostic characteristics of men with prostate cancer in the United States have changed since 1999, using data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. METHODS: The medical records of patients enrolled in CaPSURE between 1999 and 2011 were evaluated. Baseline demographics, disease features, and imaging use were assessed. Mantel-Haenszel chi-square was used to test for trends across diagnostic years. RESULTS: Between 1999 and 2011, a total of 9572 patients were diagnosed with prostate cancer and enrolled in CaPSURE at community (36), academic (3), and Veteran's Affairs (4) hospitals. Over the study period, mean age at diagnosis decreased, P <.01. In 2008-2011, a significant increase in diagnostic Gleason 7 or higher was observed relative to 1999-2001 (50% vs 36%, P <.01), congruent with recent guideline modifications of the Gleason classification system. An increase in the mean number of diagnostic biopsy cores (13.3 vs 8.3, P <.01) was also observed. A significant decrease in use of any imaging modality was seen (19% vs 45%, P <.01). Average pretreatment urinary and bowel function scores did not change, although there were significant increases in sexual function observed overall (P <.01). CONCLUSION: In the United States, several trends in the demographics and disease profile of men with newly diagnosed prostate cancer were observed over the past 12 years. Decreased imaging use and increased number of cores taken during diagnostic biopsy are in line with national urologic guidelines on prostate cancer diagnosis and management.

Ankylosing spondylitis: how diagnostic and therapeutic delay have changed over the last six decades.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive, and disabling disease, but the diagnosis is often missed and markedly delayed. An early diagnosis is important to establish a treatment to reduce disability and modify the natural course of disease. The aim of this study was to investigate the diagnostic (DD) and therapeutic (TD) delay according to the decade of diagnosis. The DD and TD correlation with radiological severity score and the new imaging techniques used in diagnosis (magnetic resonance [MRI], computerised tomography, scintigraphy for sacroiliac joints) were also investigated. METHODS: 135 AS patients (45 female and 90 male, 36.5±10.2 years old at diagnosis) with disease onset between 1950 and 2008, were investigated; the time from onset to diagnosis (DD) and treatment (TD), the New York and ASAS criteria fulfilment, the New York sacroiliac radiological score, bamboo spine presence at first visit and the new imaging technique used at diagnosis were recorded and their correlations were analysed. RESULTS: The New York and ASAS criteria were met at the first visit, by 87% and 96%, respectively. The delay from onset of symptoms to diagnosis and treatment was 9±8 and 12±11 years, respectively, but decreased significantly between different decades (p<0.001). The severity of sacroiliitis (mean 2±1; 17/135, 12.5% - IV grade sacroiliitis at diagnosis) and bamboo spine (3.7% at diagnosis) correlated with DD and TD (p<0.001). Sacroiliac MRI use at diagnosis significantly decreased both DD and TD (p>0.001 and p<0.05, respectively). CONCLUSIONS: DD and TD were correlated to radiological severity; they progressively decreased over 6 decades.

Rationale for the use of radiolabelled peptides in diagnosis and therapy.

Nuclear medicine techniques are becoming more important in imaging oncological and infectious diseases. For metabolic imaging of these diseases, antibody and peptide imaging are currently used. In recent years peptide imaging has become important, therefore the rationale for the use of peptide imaging is described in this article. Criteria for a successful peptide tracer are a high target specificity, a high binding affinity, a long metabolic stability and a high target-to-background ratio. Tracer internalization is also beneficial. For oncological imaging, many tracers are available, most originating from regulatory peptides, but penetrating peptides are also being developed. Peptides for imaging inflammatory and infectious diseases include regulatory peptides, antimicrobial peptides and others. In conclusion, for the imaging of oncological, imflammatory and infectious diseases, many promising peptides are being developed. The ideal peptide probe is characterized by rapid and specific target localization and binding with a high tumour-to-background ratio.