UNASSIGNED: Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64Cu]Cu-DOTATATE ([64Cu]Cu-[1,4,7,10-tetraazacyclododecane-N,N\',N″,N‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate).
UNASSIGNED: An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis.
UNASSIGNED: In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake.

OBJECTIVE: While immunotherapy has revolutionized the oncology field, variations in therapy responsiveness limit the broad applicability of these therapies. Diagnostic imaging of immune cell, and specifically CD8+ T cell, dynamics could allow early patient stratification and result in improved therapy efficacy and safety. In this study, we report the development of a nanobody-based immunotracer for non-invasive SPECT and PET imaging of human CD8+ T-cell dynamics.
METHODS: Nanobodies targeting human CD8β were generated by llama immunizations and subsequent biopanning. The lead anti-human CD8β nanobody was characterized on binding, specificity, stability and toxicity. The lead nanobody was labeled with technetium-99m, gallium-68 and copper-64 for non-invasive imaging of human T-cell lymphomas and CD8+ T cells in human CD8 transgenic mice and non-human primates by SPECT/CT or PET/CT. Repeated imaging of CD8+ T cells in MC38 tumor-bearing mice allowed visualization of CD8+ T-cell dynamics.
RESULTS: The nanobody-based immunotracer showed high affinity and specific binding to human CD8 without unwanted immune activation. CD8+ T cells were non-invasively visualized by SPECT and PET imaging in naïve and tumor-bearing mice and in naïve non-human primates with high sensitivity. The nanobody-based immunotracer showed enhanced specificity for CD8+ T cells and/or faster in vivo pharmacokinetics compared to previous human CD8-targeting immunotracers, allowing us to follow human CD8+ T-cell dynamics already at early timepoints.
CONCLUSIONS: This study describes the development of a more specific human CD8+ T-cell-targeting immunotracer, allowing follow-up of immunotherapy responses by non-invasive imaging of human CD8+ T-cell dynamics.

Aim: Tumor markers often remain elevated after intended curative resection of medullary thyroid carcinoma (MTC). The aim of this study was to determine the expression of αvβ3, a promising theranostics target, in MTC and its metastases. Materials & methods: Avβ3 expression was analyzed in 104 patients using a tissue microarray and correlated with clinicopathological variables and survival. Results: Cytoplasmic αvβ3 positivity was seen in 70 patients and was associated with lymph node metastases at time of initial surgery. Membranous positivity was considered positive in 30 patients and was associated with sporadic MTC. Conclusion: Avβ3 was expressed in the cytoplasm of 67% of MTC patients. Membranous expression, which is presumably most relevant for the theranostic use of αvβ3, was seen in 29%.
[Box: see text].

Myocardial perfusion single photon emission computed tomography (SPECT) is widely used in assessing coronary artery disease (CAD) owing to its proven efficacy in extensive clinical experience. Like other functional tests, myocardial SPECT is recommended for the diagnosis of obstructive CAD, risk stratification assessment, and treatment decision making. Besides quantifying left ventricular volume, global and regional function by electrocardiography (ECG)-gated acquisition, myocardial SPECT can identify myocardial ischemia, scars, stunning, and viable hibernating myocardium. It provides comprehensive functional data across the spectrum of CAD and a cost-effective strategy in patients with intermediate pre-test probability of CAD or with a history of ischemic cardiomyopathy. With ongoing advances in cardiovascular prevention and risk factor management many patients referred for testing now have a low-to-intermediate probability of CAD. Besides, CAD has become a chronic condition resulting from novel therapeutic strategies. Against this background, approaches combining anatomical and functional tests in sequence or simultaneously include coronary artery calcium score integrated with perfusion imaging or fusion SPECT/coronary computed tomography angiography (CCTA). In this review we summarize current indications for myocardial perfusion SPECT and integration of SPECT with other imaging techniques to improve diagnostic performance, patient management, and outcome prediction in CAD.

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.

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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.