Theranostics in breast cancer

INTRODUCTION : Breast cancer is a complex disease and constitutes the leading cause of cancer in women globally. Conventional treatment modalities include surgery, chemotherapy, radiation therapy, and hormonal therapy; all of these have their limitations and often result in significant side effects or toxicity. Targeted radionuclide therapy based on a theranostic approach has been successfully applied in several malignancies, such as prostate cancer, thyroid cancer, and neuro-endocrine tumours. Several studies have also highlighted the potential of theranostic applications in breast cancer. AIM : This review aims to provide an overview of the most promising current and future theranostic approaches in breast cancer. DISCUSSION : The discussion includes pre-clinical as well as clinical data on some of the most successful targets used to date. Examples of potential theranostic approaches include those targeting the Human epidermal growth factor receptor 2 (HER2) expression, angiogenesis, aspects of the tumour microenvironment, Gastrin-releasing peptide receptor (GRPR), Prostate-specific membrane antigen (PSMA) and Chemokine receptor 4 (CXCR-4) expression. Several challenges to widespread clinical implementation remain, which include regulatory approval, access to the various radiopharmaceuticals and imaging technology, cost-effectiveness, and the absence of robust clinical data. CONCLUSION : Theranostic approaches have the potential to greatly improve diagnosis, treatment, and outcomes for patients with breast cancer. More research is needed to fully explore the potential of such approaches and to identify the best potential targets, considering feasibility, costs, efficacy, side effects and outcomes.https://www.frontiersin.org/journals/nuclear-medicineam2024Nuclear MedicineSDG-03:Good heatlh and well-bein

Appropriate indications for positron emission tomography/computed tomography: College of Nuclear Physicians of the Colleges of Medicine of South Africa

Individualised patient treatment approaches demand precise determination of initial disease extent combined with early, accurate assessment of response to treatment, which is made possible by positron emission tomography/computed tomography (PET/CT). PET is a non-invasive tool that provides tomographic images and quantitative parameters of perfusion, cell viability, and proliferation and/or metabolic activity of tissues. Fusion of the functional information with the morphological detail provided by CT as PET/CT can provide clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Three large-scale national studies published by the National Oncologic PET Registry in the USA have shown that imaging with PET changes the intended patient management strategy in 36.5% to 49% of cases, with consistent results across all cancer types. The proven clinical effectiveness and growing importance of PET/CT have prompted the College of Nuclear Physicians of South Africa, in collaboration with university hospitals, to develop a list of recommendations on the appropriate use of fluorine-18-fluorodeoxyglucose (18F-FDG) and non-18F-FDG PET/CT in oncology, cardiology, neurology and infection/inflammation. It is expected that other clinical situations will be added to these recommendations, provided that they are based upon solid clinical evidence. These recommendations are intended to offer advice regarding contemporary applications of PET/CT, as well as indicating novel developments and potential future indications. The CNP believes that these recommendations will serve an important and relevant role in advising referring physicians on the appropriate use of 18F-FDG and non-18F-FDG PET/CT. More promising clinical applications will be possible in the future, as newer PET tracers become more readily available

Radionuclide Imaging of Fungal Infections and Correlation with the Host Defense Response

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response's metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. 18F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi

Monitoring Response to Therapy

Monitoring response to treatment is a key element in the management of infectious diseases, yet controversies still persist on reliable biomarkers for noninvasive response evaluation. Considering the limitations of invasiveness of most diagnostic procedures and the issue of expression heterogeneity of pathology, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively. The usefulness of F-18-FDG-PET/CT in assessing treatment response in infectious diseases is more promising than for conventional imaging. However, there are currently no clinical criteria or recommended imaging modalities to objectively evaluate the effectiveness of antimicrobial treatment. Therapeutic effectiveness is currently gauged by the patient's subjective clinical response. In this review, we present the current studies for monitoring treatment response, with a focus on Mycobacterium tuberculosis, as it remains a major worldwide cause of morbidity and mortality. The role of molecular imaging in monitoring other infections including spondylodiscitis, infected prosthetic vascular grafts, invasive fungal infections, and a parasitic disease is highlighted. The role of functional imaging in monitoring lipodystrophy associated with highly active antiretroviral therapy for human immunodeficiency virus is considered. We also discuss the key challenges and emerging data in optimizing noninvasive response evaluation. (C) 2017 Elsevier Inc. All rights reserved

Imaging fungal infections in children

Fungal infections in children rarely occur, but continue to have a high morbidity and mortality despite the development of newer antifungal agents. It is essential for these infections to be diagnosed at the earliest possible stage so appropriate treatment can be initiated promptly. The addition of high-resolution computer tomography (HR CT) has helped in early diagnosis making; however, it lacks both sensitivity and specificity. Metabolic changes precede anatomical changes and hybrid imaging with positron emission tomography (PET) integrated with imaging modalities with high anatomical resolution such as CT or magnetic resonance imaging (MRI) is likely to detect these infections at an earlier stage with higher diagnostic accuracy rates. Several authors presented papers highlighting the advantages of PET/CT in imaging fungal infections. These papers, however, usually involve a limited number of patients and mostly adults. Fungal infections behave different in children than in adults, since there are differences in epidemiology, imaging findings, and response to treatment with antifungal drugs. This paper reviews the literature and explores the use of hybrid imaging for diagnosis and therapy decision making in children with fungal infections

Appropriate indications for positron emission tomography/computed tomography, 2015

These recommendations are intended to serve an important and relevant role in advising referring physicians on the appropriate use of 18F-fluorodeoxyglucose (18F-FDG) and non-18F-FDG positron emission tomography/computed tomography (PET/CT), which can be a powerful tool in patient management in oncology, cardiology, neurology and infection/inflammation. PET is a non-invasive molecular imaging tool that provides tomographic images and quantitative parameters of perfusion, cell viability, proliferation and/or metabolic activity of tissues. These images result from the use of different substances of biological interest (sugars, amino acids, metabolic precursors, hormones) labelled with positron-emitting radionuclides (PET radiopharmaceuticals). Fusion of the aforementioned important functional information with the morphological detail provided by CT as PET/CT provides clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Hence PET/CT is currently the most widely used molecular imaging technology for a patient-tailored treatment approach. In these recommendations we outline which oncological and non-oncological indications are appropriate for PET/CT. Once each combination of pathology and clinical indication is defined, a recommendation is given as: 1. Recommended; 2. Recommended in select cases; 3. May be considered; or 4. Not recommended

Impact of optimized PET imaging conditions on F-18-FDG uptake quantification in patients with apparently normal aortas

Background The cardiovascular committee of the European Association of Nuclear Medicine (EANM) recently published recommendations on imaging conditions to be observed during F-18-FDG PET imaging of vascular inflammation. This study aimed to evaluate the impact of applying these optimized imaging conditions on PET quantification of arterial F-18-FDG uptake. Methods and Results Fifty-seven patients were prospectively recruited to undergo an early F-18-FDG PET/CT imaging at 60 minutes and repeat delayed imaging at >= 120 minutes post tracer injection. Routine oncologic F-18-FDG PET protocol was observed for early imaging, while delayed imaging parameters were optimized for vascular inflammation imaging as recommended by the EANM. Aortic SUVmax of the ascending aorta and SUVmean from the lumen of the superior vena cava (SVC SUVmean) were obtained on early and delayed imaging. Target-to-background ratio (TBR) was obtained for the early and delayed imaging. Aortic SUVmax increased by a mean of 70%, while SVC SUVmean decreased by a mean of 52% between early and delayed imaging (P 180 minutes. Aortic SUVmax significantly increased at imaging time-points between 120 and 180 minutes. No significant improvement in aortic SUVmax was seen at imaging time-points beyond 180 minutes. Conclusions F-18-FDG PET imaging conditions optimized for vascular inflammation imaging lead to an improved quantification through an increase in the quantified vascular tracer uptake and decrease in blood-pool background activity

Recent innovations and nano-delivery of actinium-225 : a narrative review

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the 225Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on 225Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of -particles in targeted alpha therapy (TAT) with an emphasis on 225Ac is discussed. Quality control measures in the preparation of 225Ac-conjugates are also highlighted.Nuclear Medicine Research Infrastructure (NuMeRI).https://www.mdpi.com/journal/pharmaceuticsam2024Nuclear MedicineSDG-03:Good heatlh and well-bein

Radionuclide Imaging of Invasive Fungal Disease in Immunocompromised Hosts

Invasive fungal disease (IFD) leads to increased mortality, morbidity, and costs of treatment in patients with immunosuppressive conditions. The definitive diagnosis of IFD relies on the isolation of the causative fungal agents through microscopy, culture, or nucleic acid testing in tissue samples obtained from the sites of the disease. Biopsy is not always feasible or safe to be undertaken in immunocompromised hosts at risk of IFD. Noninvasive diagnostic techniques are, therefore, needed for the diagnosis and treatment response assessment of IFD. The available techniques that identify fungal-specific antigens in biological samples for diagnosing IFD have variable sensitivity and specificity. They also have limited utility in response assessment. Imaging has, therefore, been applied for the noninvasive detection of IFD. Morphologic imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is the most applied technique. These techniques are neither sufficiently sensitive nor specific for the early diagnosis of IFD. Morphologic changes evaluated by CT and MRI occur later in the disease course and during recovery after successful treatment. These modalities may, therefore, not be ideal for early diagnosis and early response to therapy determination. Radionuclide imaging allows for targeting the host response to pathogenic fungi or specific structures of the pathogen itself. This makes radionuclide imaging techniques suitable for the early diagnosis and treatment response assessment of IFD. In this review, we aimed to discuss the interplay of host immunity, immunosuppression, and the occurrence of IFD. We also discuss the currently available radionuclide probes that have been evaluated in preclinical and clinical studies for their ability to detect IFD.</p