Purpose
This review discusses the current state of prostate-specific membrane antigen (PSMA)-based alpha therapy of metastatic castration-resistant prostate cancer (mCRPC). With this in-depth ...discussion on the growing field of PSMA-based alpha therapy (PAT), we aimed to increase the interactions between basic scientists and physician–scientists in order to advance the field.
Methods
To achieve this, we discuss the potential, current status, and opportunities for alpha therapy and strategies, attempted to date, and important questions that need to be addressed. The paper reviews important concepts, including whom to treat, how to treat, what to expect regarding treatment outcome, and toxicity, and areas requiring further investigations.
Results
There is much excitement about the potential of this field. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other conventional therapies.
Conclusion
A better understanding of the strengths and limitations of PAT may help in creating an effective therapy for mCRPC and design a rational combinatorial approach to treatment by targeting different tumor pathways.
Non-invasive imaging of hypoxia plays a role in monitoring the body’s adaptive response or the development of pathology under hypoxic conditions. Various techniques to image hypoxia have been ...investigated with a shift towards the use of molecular imaging using PET/CT. The role of hypoxia-specific radiopharmaceuticals such as radiolabelled nitroimidazoles is well documented particularly in the oncologic setting. With the increasing utilisation of in-house labelling with a PET benchtop generator, such as the
68
Ge/
68
Ga generator, the use of
68
Ga-labelled hypoxic radiopharmaceuticals in the clinical setting is developing. Since hypoxia plays a role in various pathologic states including infectious disease such as TB, there is a need to explore the potential application of
68
Ga-labelled hypoxia seeking radiopharmaceuticals beyond oncology. The purpose of this review is to describe the developments of
68
Ga-labelled hypoxic radiopharmaceuticals including the various chelators that have been investigated. Further, the role of hypoxia imaging in various pathologies is discussed with particular emphasis on the potential clinical applications of hypoxia PET/CT in TB.
Inflammation is an important component of several chronic and debilitating diseases that result in significant morbidity and mortality. This is best evidenced within the cardiovascular system where ...it may manifest as atherosclerosis or myocarditis, and at the extreme end of the spectrum as myocardial infarction, ventricular remodeling, or cardiac failure. Early non-invasive detection and monitoring of inflammation in these and other settings may better guide patient management with resultant improved outcomes.
Key role players in inflammation pathophysiology include chemokines, macrophages, neutrophils, fibroblasts, integrins, and reactive oxygen species, amongst others. Examples of receptor expression and over-expression include somatostatin receptors, CXCR4-, folate-, mannose-, TSPO- receptors and secretion of various vascular adhesion molecules (such as VCAM and ICAM).
Gallium-68-based PET offers imaging possibilities for nearly all the major pathophysiological role players in inflammation, with mounting recent interest in macrophage differentiation, various forms of receptor expression and secretion of chemokines and vascular adhesion molecules. The advantages in terms of logistics and costs of having generator-produced PET probes available is well known, and a 68Ga-based tracer provides easily translatable theranostic possibilities to especially Lu-177.
Some of the more versatile and better validated Ga-68-based inflammation probes include 68Ga-DOTA-TATE/NOC/TOC, 68Ga-NOTA-RGD, 68Ga-CXCR4, 68Ga-citrate and 68Ga-FAPI.
Prostate cancer (PCa) causes significant morbidity and mortality in men globally. While localized PCa may be managed with curative intent by surgery and/or radiation therapy, the management of ...advanced hormone resistant metastatic disease (mCRPC) is more challenging. Theranostics is a principle based on the ability to use an organ specific ligand and label it to both a diagnostic and a therapeutic agent. The overexpression of prostate specific membrane antigen (PSMA) on prostate cancer cells creates a unique opportunity for development of targeted radionuclide therapy. The use of both beta and alpha emitting particles has shown great success. Several clinical trials have been initiated assessing the efficacy and safety profile of these radionuclide agents. The results are encouraging with PSMA directed radioligand therapy performing well in patients who have exhausted all other standard treatment options. Future studies need to assess the timing of introduction of these radionuclide therapies in the management schema of mCRPC. Drugs or therapies are not without side effects and targeted radionuclide therapies presents a new set of toxicities including xerostomia and myelosuppression. New therapeutic strategies are being explored to improve outcomes while keeping toxicities to a minimum. This review aims to look at the various PSMA labelled tracers that form part of the theragnostic approach and subsequently delve into the progress made in the area of radionuclide therapy.
The Role of PET/CT in Breast Cancer Hadebe, Bawinile; Harry, Lerwine; Ebrahim, Tasmeera ...
Diagnostics (Basel),
02/2023, Volume:
13, Issue:
4
Journal Article
Peer reviewed
Open access
Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases (11.7%), followed by lung cancer (11.4%) The current literature ...and the National Comprehensive Cancer Network (NCCN) guidelines state that
F-FDG PET/CT is not routine for early diagnosis of breast cancer, and rather PET/CT scanning should be performed for patients with stage III disease or when conventional staging studies yield non-diagnostic or suspicious results because this modality has been shown to upstage patients compared to conventional imaging and thus has an impact on disease management and prognosis. Furthermore, with the growing interest in precision therapy in breast cancer, numerous novel radiopharmaceuticals have been developed that target tumor biology and have the potential to non-invasively guide the most appropriate targeted therapy. This review discusses the role of
F-FDG PET and other PET tracers beyond FDG in breast cancer imaging.
The progression of coronavirus disease 2019 (COVID-19), resulting from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be influenced by both genetic and environmental ...factors. Several viruses hijack the host genome machinery for their own advantage and survival, and similar phenomena might occur upon SARS-CoV-2 infection. Severe cases of COVID-19 may be driven by metabolic and epigenetic driven mechanisms, including DNA methylation and histone/chromatin alterations. These epigenetic phenomena may respond to enhanced viral replication and mediate persistent long-term infection and clinical phenotypes associated with severe COVID-19 cases and fatalities. Understanding the epigenetic events involved, and their clinical significance, may provide novel insights valuable for the therapeutic control and management of the COVID-19 pandemic. This review highlights different epigenetic marks potentially associated with COVID-19 development, clinical manifestation, and progression.
The process of inflammation (with or without infection) forms part of essentially every major debilitating disease. Early detection and accurate distinction of inflammation from infection are ...important to optimize and individualize therapy. Nuclear medicine is ideally suited for the detection of pathologic changes early on and is able to target a magnitude of role players involved in the aforementioned processes. Hybrid modalities such as PET/CT and PET/MRI offer high spatial resolution that combines morphologic and pathophysiological changes and add various quantification possibilities that are preferable in these settings. It follows then that the development of PET radiopharmaceuticals is imperative to make use of these latest advances. Gallium-68 (Ga-68)-based tracers are exceptionally well suited to these indications, considering the year-round availability from a single generator, the relative cost-effectiveness, and relative ease of labeling. Over the past few years, the development of Ga-68-based tracers has understandably exploded with a recent growing interest in infection and inflammation imaging. This review aims to highlight some of the most important and interesting advances made with Ga-68-based PET/CT in the field of infection and inflammation imaging.
Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression ...of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may benefit from novel therapies targeting CXCR4. In addition, its therapeutic partners 177Lu- and 90Y-Pentixather have been investigated in the treatment of patients with advanced haematological malignancies, and initial studies have shown a good treatment response in metabolically active lesions. 68Ga-Pentixafor in solid tumours complements 18F-FDG by providing prognostic information and selecting patients who may benefit from therapies targeting CXCR4. This review summarises the available literature on the potential applications of 68Ga-Pentixafor in solid tumours.
Tuberculosis (TB) lesions in humans have been proven to be severely hypoxic with hypoxia leading to latency and dormancy of disease. Dormant TB lesions become less susceptible to standard TB ...treatment regimens with varying responses to treatment but may have increased susceptibility to nitroimidazole drugs. This in turn implies that positron emission tomography / computed tomography (PET/CT) imaging with radiolabelled nitroimidazoles may identify patients who will benefit from treatment with antimicrobial agents that are active against anaerobic bacteria. This case series aims to highlight the hypoxic uptake and retention of a novel 68Ga‐labelled hypoxia‐seeking agent in TB lesions at different time points during anti‐TB therapy using PET/CT imaging. Patients with confirmed TB underwent whole‐body PET/CT after administration of a 68Ga‐nitroimidazole derivative at baseline and follow‐up. Images were analysed both qualitatively and semi‐quantitatively. Hypoxic uptake and change in uptake over time were analysed using lesion‐to‐muscle ratio (LMR) and lesion‐to‐blood ratio (LBR). 68Ga‐nitroimidazole avid lesions were demonstrated most frequently in the upper lobes of the lung. Low‐grade hypoxic uptake was visualised in areas of consolidation, cavitation, nodules and lymph nodes. From baseline to follow‐up imaging, the LMR increased with persistent hypoxic load despite morphologic improvement. This case series highlights the dynamic hypoxic microenvironment in TB lesions. From these initial data, it appears that 68Ga‐nitroimidazole is a promising candidate for monitoring hypoxic load in patients diagnosed with TB. Such imaging could identify patients who would benefit from individualised therapy targeting other mechanisms in the TB microenvironment with the intention to predict or improve treatment response.
There is increasing application of PET/CT imaging in infectious diseases such as tuberculosis. Imaging potential stressors such as hypoxia, using a novel Ga‐68 labelled hypoxia seeking agent, has the potential to identify patients who may benefit from individualised treatment strategies. This case series highlights promising initial results of hypoxia PET/CT imaging in tuberculosis.
PDF
