Nuclear medicine imaging modalities to detect incidentalomas and their impact on patient management: a systematic review.

PURPOSE: This systematic review aims to investigate the role of nuclear imaging techniques in detecting incidentalomas and their impact on patient management. METHODS: Following PRISMA guidelines, a comprehensive literature search was conducted from February to May 2022. Studies in English involving patients undergoing nuclear medicine studies with incidental tumor findings were included. Data on imaging modalities, incidentaloma characteristics, management changes, and follow-up were extracted and analyzed. RESULTS: Ninety-two studies involving 64.884 patients were included. Incidentalomas were detected in 611 cases (0.9%), with thyroid being the most common site. PET/CT with FDG and choline tracers showed the highest incidentaloma detection rates. Detection of incidentalomas led to a change in therapeutic strategy in 59% of cases. Various radiotracers demonstrated high sensitivity for incidentaloma detection, particularly in neuroendocrine tumors and prostate cancer. CONCLUSION: Nuclear imaging techniques play a crucial role in detecting incidentalomas, leading to significant changes in patient management. The high sensitivity of these modalities highlights their potential in routine oncology follow-up protocols. Future directions may include enhancing spatial resolution and promoting theranostic approaches for improved patient care.

The Cardiac Mirage: A Case of Ambiguous Chest Pain.

background: Coronary artery disease (CAD) can masquerade as other illnesses due to its varied presentations, the co-existence of other chest pain etiologies, and the limitations of diagnostic modalities. Case report: We present a case of ambiguous chest pain due to multiple possible etiologies, including acute coronary syndrome (ACS), where initial cardiological testing yielded negative results. This led to a delay of 112 days in establishing the diagnosis and initiating appropriate treatment. Conclusion: This case emphasizes the crucial role of clinical context and risk stratification in chest pain evaluation. It is imperative to interpret cardiovascular test results carefully, taking into account the sensitivities, specificities, scope, and limitations of the utilized modalities.

Assessment of Radiolabelled Derivatives of R954 for Detection of Bradykinin B1 Receptor in Cancer Cells: Studies on Glioblastoma Xenografts in Mice.

Bradykinin B1 receptor (B1R) has garnered attention as a cancer therapeutic and diagnostic target. Several reports on radiolabelled derivatives of B1R antagonists have shown favourable properties as imaging agents in cells highly expressing hB1R following transfection. In the present study, we assessed whether radiolabelled probes can detect B1R endogenously expressed in cancer cells. To this end, we evaluated 111In-labelled derivatives of a B1R antagonist ([111In]In-DOTA-Ahx-R954) using glioblastoma cell lines (U87MG and U251MG) with different B1R expression levels. Cellular uptake studies showed that the specific accumulation of [111In]In-DOTA-Ahx-R954 in U87MG was higher than that in U251MG, which correlated with B1R expression levels. Tissue distribution in U87MG-bearing mice revealed approximately 2-fold higher radioactivity in tumours than in the muscle in the contralateral leg. The specific accumulation of [111In]In-DOTA-Ahx-R954 in the tumour was demonstrated by the reduction in the tumour-to-plasma ratios in nonlabelled R954-treated mice. Moreover, ex vivo autoradiographic images revealed that the intratumoural distribution of [111In]In-DOTA-Ahx-R954 correlated with the localisation of B1R-expressing glioblastoma cells. In conclusion, we demonstrated that [111In]In-DOTA-Ahx-R954 radioactivity correlated with B1R expression in glioblastoma cells, indicating that radiolabelled derivatives of the B1R antagonist could serve as promising tools for elucidating the involvement of B1R in cancer.

Nuclear-Based Labeling of Cellular Immunotherapies: A Simple Protocol for Preclinical Use.

Labeling and tracking existing and emerging cell-based immunotherapies using nuclear imaging is widely used to guide the preclinical phases of development and testing of existing and new emerging off-the-shelf cell-based immunotherapies. In fact, advancing our knowledge about their mechanism of action and limitations could provide preclinical support and justification for moving towards clinical experimentation of newly generated products and expedite their approval by the Food and Drug Administration (FDA).Here we provide the reader with a ready to use protocol describing the labeling methodologies and practical procedures to render different candidate cell therapies in vivo traceable by nuclear-based imaging. The protocol includes sufficient practical details to aid researchers at all career stages and from different fields in familiarizing with the described concepts and incorporating them into their work.

Contemporary Role of Positron Emission Tomography (PET) in Endocarditis: A Narrative Review.

Endocarditis, a serious infectious disease, remains a diagnostic challenge in contemporary clinical practice. The advent of advanced imaging modalities has contributed significantly to the improved understanding and management of this complex disease. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has shown remarkable potential in improving the diagnostic accuracy of endocarditis. In the update of the Modified Duke Criteria, in 2023, The International Society for Cardiovascular Infectious Diseases (ISCVID) Working Group recognized specific 18F-FDG PET/CT findings as a major diagnostic criterion, particularly in patient with prosthetic valve endocarditis. The ability of PET to visualize metabolic activity allows for the identification of infective foci and could differentiate between infective and non-infective processes. This review examines the clinical utility of PET in differentiating infective endocarditis from other cardiovascular pathologies, highlighting its sensitivity and specificity in detecting native and prosthetic valve infections, including patients with transcatheter aortic valve implantation (TAVI), cardiac implantable devices (CIEDs), and left ventricular assistance devices (LVAD). Also, practical aspects and indications are illustrated to optimize the quality of imaging and reduce potential false positive results. In conclusion, the current use of PET in endocarditis has become a valuable diagnostic tool; as technological advances continue, PET will play an increasingly important role in the multidisciplinary approach to the management of endocarditis.

Recent Advancements in Radiopharmaceuticals for Infection Imaging.

COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine, with its powerful scintigraphic, single photon emission computer tomography (SPECT), and positron emission tomography (PET) imaging modalities, has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals, there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled antifungals for fungal infections imaging, radiolabeled pathogen-specific antibodies, and molecular engineered constructs. In this chapter, we discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.

TMVP1448, a novel peptide improves detection of primary tumors and metastases by specifically targeting VEGFR-3.

Lymphangiogenesis at primary tumor and draining lymph nodes plays a pivotal role in tumor metastasis, which has been demonstrated to be regulated by the vascular endothelial growth factor receptor 3 (VEGFR-3) pathway. However, the effect of molecular imaging peptides, which specifically bind VEGFR-3, in tracing tumors remains unclear. We prepared a novel peptide, TMVP1448, with high-affinity to VEGFR-3. The dissociation constant (KD) of TMVP1448 with VEGFR-3 was 7.07 ×10-7 M. In vitro cellular assay showed that TMVP1448 could bind specifically with VEGFR-3. Near infrared imaging results showed that Cy7-TMVP1448 was able to accurately trace primary and metastatic cancers, and PET/CT results showed that [68Ga]Ga-DOTA-TMVP1448 was superior to commonly used radiotracers 18F-FDG. Additionally, no significant negative effect of TMVP1448 was found in mice. Our results suggested that TMVP1448 had great potential for future clinical applications in fluorescence imaging and nuclear imaging of tumors.

The Role of Multimodality Imaging in Cardiomyopathy.

PURPOSE OF REVIEW: There has been increasing use of multimodality imaging in the evaluation of cardiomyopathies. RECENT FINDINGS: Echocardiography, cardiac magnetic resonance (CMR), cardiac nuclear imaging, and cardiac computed tomography (CCT) play an important role in the diagnosis, risk stratification, and management of patients with cardiomyopathies. Echocardiography is essential in the initial assessment of suspected cardiomyopathy, but a multimodality approach can improve diagnostics and management. CMR allows for accurate measurement of volumes and function, and can easily detect unique pathologic structures. In addition, contrast imaging and parametric mapping enable the characterization of tissue features such as scar, edema, infiltration, and deposition. In non-ischemic cardiomyopathies, metabolic and molecular nuclear imaging is used to diagnose rare but life-threatening conditions such amyloidosis and sarcoidosis. There is an expanding use of CCT for planning electrophysiology procedures such as cardioversion, ablations, and device placement. Furthermore, CCT can evaluate for complications associated with advanced heart failure therapies such as cardiac transplant and mechanical support devices. Innovations in multimodality cardiac imaging should lead to increased volumes and better outcomes.

AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia.

Rationale: AXL expression has been identified as a prognostic factor in acute myeloid leukemia (AML) and is detectable in approximately 50% of AML patients. In this study, we developed AXL-specific single domain antibodies (sdAbs), cross-reactive for both mouse and human AXL protein, to non-invasively image and treat AXL-expressing cancer cells. Methods: AXL-specific sdAbs were induced by immunizing an alpaca with mouse and human AXL proteins. SdAbs were characterized using ELISA, flow cytometry, surface plasmon resonance and the AlphaFold2 software. A lead compound was selected and labeled with 99mTc for evaluation as a diagnostic tool in mouse models of human (THP-1 cells) or mouse (C1498 cells) AML using SPECT/CT imaging. For therapeutic purposes, the lead compound was fused to a mouse IgG2a-Fc tail and in vitro functionality tests were performed including viability, apoptosis and proliferation assays in human AML cell lines and primary patient samples. Using these in vitro models, its anti-tumor effect was evaluated as a single agent, and in combination with standard of care agents venetoclax or cytarabine. Results: Based on its cell binding potential, cross-reactivity, nanomolar affinity and GAS6/AXL blocking capacity, we selected sdAb20 for further evaluation. Using SPECT/CT imaging, we observed tumor uptake of 99mTc-sdAb20 in mice with AXL-positive THP-1 or C1498 tumors. In THP-1 xenografts, an optimized protocol using pre-injection of cold sdAb20-Fc was required to maximize the tumor-to-background signal. Besides its diagnostic value, we observed a significant reduction in tumor cell proliferation and viability using sdAb20-Fc in vitro. Moreover, combining sdAb20-Fc and cytarabine synergistically induced apoptosis in human AML cell lines, while these effects were less clear when combined with venetoclax. Conclusions: Because of their diagnostic potential, sdAbs could be used to screen patients eligible for AXL-targeted therapy and to follow-up AXL expression during treatment and disease progression. When fused to an Fc-domain, sdAbs acquire additional therapeutic properties that can lead to a multidrug approach for the treatment of AXL-positive cancer patients.

Emergency department imaging utilization post-transcatheter aortic valve replacement: single institution 7-year experience.

PURPOSE: This study aims to highlight presentations, acute findings and imaging phenotypes of patients presenting to the emergency department (ED) within 30 days of a transcatheter aortic valve replacement (TAVR). METHODS: A retrospective review of patients diagnosed with aortic valve disease who underwent a TAVR between Jan 2015 and Nov 2021 at a large academic medical center was completed. From an initial 1271 patients, 146 were included based on their presentation to the ED within 30 days post-TAVR procedure. Patient data, including ED presentation details and imaging results, were recorded and de-identified. RESULTS: Of the 146 post-TAVR patients, there were 168 ED visits within 30 days. The median time to ED after TAVR was 12 days. Respiratory symptoms were the most common complaint (27%). Neurological (23%) and cardiovascular symptoms (18%) followed. Cross-sectional imaging was conducted 250 times across visits, with an average of 1.7 scans per patient. CTs were most frequently used, followed by ultrasounds, especially echocardiograms and duplex extremity vasculature ultrasounds. 30.1% of patients had acute findings from imaging. Specific findings included heart failure (5.5%), access site complications (5.5%), pneumonia (5.5%), intracranial pathologies (3.4% for strokes and 0.7% for hematoma), and pleural effusion (3.4%). Echocardiograms and CTA chest were most associated with significant acute findings. CONCLUSION: Our study highlights the vital role of early and accurate imaging in post-TAVR patients within 30 days post-procedure. As transcatheter approaches rise in popularity, emergency radiologists become instrumental in diagnosing common post-procedural presentations. Continued research is essential to devise post-discharge strategies to curtail readmissions and related costs. Proper imaging ensures prompt, effective care, enhancing overall patient outcomes.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Advances in Multi-Modality Imaging in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterized by abnormal growth of the myocardium with myofilament disarray and myocardial hyper-contractility, leading to left ventricular hypertrophy and fibrosis. Where culprit genes are identified, they typically relate to cardiomyocyte sarcomere structure and function. Multi-modality imaging plays a crucial role in the diagnosis, monitoring, and risk stratification of HCM, as well as in screening those at risk. Following the recent publication of the first European Society of Cardiology (ESC) cardiomyopathy guidelines, we build on previous reviews and explore the roles of electrocardiography, echocardiography, cardiac magnetic resonance (CMR), cardiac computed tomography (CT), and nuclear imaging. We examine each modality's strengths along with their limitations in turn, and discuss how they can be used in isolation, or in combination, to facilitate a personalized approach to patient care, as well as providing key information and robust safety and efficacy evidence within new areas of research.

Best Practices in Nuclear Imaging for the Diagnosis of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in KSA: The Eagle Eyes of Local Experts.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient's echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.

The Impact of Dual and Triple Energy Window Scatter Correction on I-123 Postsurgical Thyroid SPECT/CT Imaging Using a Phantom with Small Sizes of Thyroid Remnants.

I-123 is preferential over I-131 for diagnostic SPECT imaging after a thyroidectomy to determine the presence and size of residual thyroid tissue for radioiodine ablation. Scattering degrades the quality of I-123 SPECT images, primarily due to the penetration of high-energy photons into the main photopeak. The objective of this study was to quantitatively and qualitatively investigate the impact of two widely used window-based scatter correction techniques, the dual energy window (DEW) and triple energy window (TEW) techniques, in I-123 postsurgical SPECT/CT thyroid imaging using an anthropomorphic phantom with small sizes of remnants and anatomically correct surrounding structures. For this purpose, non-scatter-corrected, DEW and TEW scatter-corrected SPECT/CT acquisitions were performed for 0.5-10 mL remnants within a phantom, with 0.5-12.6 MBq administered activities within the remnants, and without and with background-to-remnant activity ratios of 5% and 10%. The decrease in photons, the noise and non-uniformity in the background region due to scatter correction were measured, as well as the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) from small remnants. The images were also visually evaluated by two experienced nuclear medicine physicians. Scatter correction decreased photons to a higher extent in larger regions than smaller regions. Larger remnants yielded higher SNR and CNR values, particularly at lower background activities. It was found from the quantitative analysis and the qualitative evaluation that TEW scatter correction performed better than DEW scatter correction, particularly at higher background activities, while no significant differences were reported at lower background activities. Scatter correction should be applied in I-123 postsurgical SPECT/CT imaging to improve the image contrast and detectability of small remnants within the background.

Optimizing cardiac amyloidosis assessment: utility of 1-h and 3-h 99mTc-PYP imaging.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of heart failure in elderly patients. In this study, our primary objective was to explore the diverse applications and temporal significance of 1-h and 3-h imaging using 99mTc-PYP in the context of ATTR-CM. Additionally, we compared tracer kinetics in the heart and bone to comprehensively assess the diagnostic advantages and time-related considerations associated with these two incubation periods. METHODS: Twenty-seven patients at Nagasaki University Hospital who underwent 99mTc-PYP planar, and SPECT cardiac imaging were classified into two groups (ATTR-CM-positive and -negative groups) based on the American Heart Association statement. Cardiac retention was assessed with both a semiquantitative visual score and a quantitative analysis. To assess bone accumulation, a ROI with an equal volume was drawn on the sternum and calculated as the bone-to-contralateral ratio (B/CL). We also evaluated correlation between heart-to-contralateral lung (H/CL) ratio and left ventricular wall thickness. RESULTS: Among patients who underwent 99mTc-PYP imaging, the H/CL ratio was significantly higher at 1 h than at 3 h regardless of the group (from 2.20 ± 0.36 to 1.99 ± 0.35, p < 0.01 in the positive group and from 1.35 ± 0.12 to 1.19 ± 0.21, p = 0.01 in the negative group). The gap of H/CL between highest H/CL of negative case and lowest H/CL of positive case was narrower in 3 h. On the other hand, correlation between H/CL and left ventricular posterior wall thickness tends to be clearer in 3 h (p = 0.12, r = 0.30 for 1 h, p = 0.04, r = 0.39 at 3 h). CONCLUSION: Our study suggests that both 1-h and 3-h incubation times for 99mTc-PYP imaging have different benefits for ATTR cardiac amyloidosis. A one-hour incubation may be preferable for differential diagnostic purposes, while a three-hour incubation may provide greater utility in evaluating disease severity.

Inverse radon transform with deep learning: an application in cardiac motion correction.

Objective. This paper addresses performing inverse radon transform (IRT) with artificial neural network (ANN) or deep learning, simultaneously with cardiac motion correction (MC). The suggested application domain is cardiac image reconstruction in emission or transmission tomography where IRT is relevant. Our main contribution is in proposing an ANN architecture that is particularly suitable for this purpose.Approach. We validate our approach with two types of datasets. First, we use an abstract object that looks like a heart to simulate motion-blurred radon transform. With the known ground truth in hand, we then train our proposed ANN architecture and validate its effectiveness in MC. Second, we used human cardiac gated datasets for training and validation of our approach. The gating mechanism bins data over time using the electro-cardiogram (ECG) signals for cardiac motion correction.Main results. We have shown that trained ANNs can perform motion-corrected image reconstruction directly from a motion-corrupted sinogram. We have compared our model against two other known ANN-based approaches.Significance. Our method paves the way for eliminating any need for hardware gating in medical imaging.

The Role of Multimodality Imaging in Patients with Congenital Heart Disease and Infective Endocarditis.

Infective endocarditis (IE) represents an important medical challenge, particularly in patients with congenital heart diseases (CHD). Its early and accurate diagnosis is crucial for effective management to improve patient outcomes. Multimodality imaging is emerging as a powerful tool in the diagnosis and management of IE in CHD patients, offering a comprehensive and integrated approach that enhances diagnostic accuracy and guides therapeutic strategies. This review illustrates the utilities of each single multimodality imaging, including transthoracic and transoesophageal echocardiography, cardiac computed tomography (CCT), cardiovascular magnetic resonance imaging (CMR), and nuclear imaging modalities, in the diagnosis of IE in CHD patients. These imaging techniques provide crucial information about valvular and intracardiac structures, vegetation size and location, abscess formation, and associated complications, helping clinicians make timely and informed decisions. However, each one does have limitations that influence its applicability.

Theranostics with photodynamic therapy for personalized medicine: to see and to treat.

Photodynamic Therapy (PDT) is an approved treatment modality, which is presently receiving great attention due to its limited invasiveness, high selectivity and limited susceptibility to drug resistance. Another related research area currently expanding rapidly is the development of novel theranostic agents based on the combination of PDT with different imaging technologies, which allows for both therapy and diagnosis. This combination can help to address issues of suboptimal biodistribution and selectivity through regional imaging, while therapeutic agents enable an effective and personalized therapy. In this review, we describe compounds, whose structures combine PDT photosensitizers with different imaging probes - including examples for near-infrared optical imaging, magnetic resonance imaging (MRI) and nuclear imaging (PET or SPECT), generating novel theranostic drug candidates. We have intentionally focused our attention on novel compounds, which have already been investigated preclinically in vivo in order to demonstrate the potential of such theranostic agents for clinical applications.

Degradation Adaptability Assessment of Semisolid Powder Molded Mg-Zn-Mn Alloys for Orthopedic Applications.

Semisolid powder molding was used to prepare the medical Mg-6Zn alloy; in order to further improve its degradation adaptability, 0.5 and 1 wt % Mn were added. Then, the effect of the forming temperature (540, 560, 580, and 600 °C) on the in vitro degradation behavior of the prepared Mg-6Zn-xMn (x = 0.5, 1 wt %) was analyzed, and the optimized alloy was obtained. Finally, the biocompatibility and in vivo degradation performance of the optimized and Mn-free alloys were evaluated. Importantly, single-photon emission tomographic imaging (SPECT/CT) was first applied to monitor the in vivo degradation process. The results show that the corrosion mechanism of the Mn-free alloy is microgalvanic corrosion control with corrosive pitting. After adding Mn, the in vitro degradation rate decreases by half (0.17 ± 0.01 mm/year) as the forming temperature increases to 600 °C, and Mg-6Zn-1Mn prepared at 600 °C is the optimized alloy. Mn addition improves the corrosion product film protection and discontinuous secondary phases, and thus, the corrosion mechanism is changed to corrosive pitting control. Additionally, semisolid powder molding is an easy method to prepare alloys with low average pore interconnectivity (<10%), which is helpful for slowing down the degradation rate. The Mn-containing alloy has better biocompatibility, with a cytotoxicity of grade 0-1, due to its lower degradation rate. The in vivo corrosion rate of the Mn-free alloy is 0.19 mm/year after 28 days of implantation, which was precisely detected by SPECT/CT in real-time. The long-term in vivo degradation adaptability of Mn-free and Mn-containing alloys was not correctly presented, which may be due to the unreasonable bone defect model causing implant displacement. However, both of these alloys cause no obvious inflammation and show good healing. In summary, semisolid powder molding is a potentially promising technique to prepare medical Mg alloys, and nuclear imaging is an effective in vivo degradation evaluation method.