Radionuclide Imaging of Infective Endocarditis.

Infective endocarditis (IE) is associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient management. Due to difficulties in the diagnosis, a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data, and imaging data is used. Imaging, including echocardiography, molecular imaging techniques, and coronary CT angiography (CTA) is central to detect infections involving heart valves and implanted cardiovascular devices, also allowing for early detection of septic emboli and metastatic. This article describes the main clinical application of white blood cell SPECT/CT and [18F]FDG-PET/CT and CTA in IE and infections associated with cardiovascular implantable electronic devices.

Imaging of Endocarditis and Cardiac Device-Related Infections: An Update.

IE is a deadly disease requiring prompt diagnosis for adequate patient's management. The diagnosis requires the integration of clinical signs, microbiology data and imaging data and proper discussion within a multidisciplinary team, the endocarditis team. Since the introduction of 18F-FDG-PET/CT and WBC SPECT/CT in the diagnostic algorithm of PVE the nuclear medicine imaging specialists is active part of the Endocarditis Team, requiring proper knowledge of dedicated imaging acquisition protocols, expertise for imaging reading and interpretations to select the best test or combination of tests for each specific clinical situation. In this manuscript, we will review the main technical aspects of each imaging procedure, the most recent literature with specific regards to special challenging populations and provide clinical examples.

Role of Multimodal Imaging in Patients With Suspected Infections After the Bentall Procedure.

Purpose: This study aimed to assess the diagnostic performances of multimodal imaging [i.e., white blood cell single-photon emission computed tomography/CT (99mTc-HMPAO-WBC SPECT/CT) and 18-fluoride-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT)] in patients with suspected infection after the Bentall procedure, proposing new specific diagnostic criteria for the diagnosis. Methods: Between January 2009 and December 2019, we selected within a cardiovascular infections registry, 76 surgically treated patients (27 women and 49 men, median 66 years, and range 29-83 years). All the patients underwent molecular imaging for a suspected infection after the replacement of the aortic valve and ascending aorta according to the Bentall procedure. We analyzed 98 scans including 49 99mTc-WBC and 49 [18F]FDG PET/CT. A total of 22 patients with very early/early suspected infection (<3 months after surgery) were imaged with both the techniques. Positive imaging was classified according to the anatomical site of increased uptake: to the aortic valve (AV), to both the AV and AV tube graft (AVTG) or to the TG, to surrounding tissue, and/or to extracardiac sites (embolic events or other sites of concomitant infection). Standard clinical workup included in all the patients having echocardiography/CT, blood culture, and the Duke criteria. Pretest probability and positive/negative likelihood ratio were calculated. Sensitivity and specificity of 99mTc labeled hexamethylpropylene amine oxime-WBC SPECT/CT (99mTc-HMPAO-WBC SPECT/CT) and [18F]FDG PET/CT imaging were calculated by using microbiology (n = 35) or clinical follow-up (n = 41) as final diagnosis. 99mTc-HMPAO-WBC scintigraphy and [18F]FDG PET/CT findings were compared with 95% CIs by using the McNemar test to those of echocardiography/CT, blood culture, and the Duke criteria. Results: Sensitivity, specificity, and accuracy of 99mTc-HMPAO-WBC were 86, 92, and 88%, respectively, with a slightly higher sensitivity for tube graft infection (TGI) as compared to isolated AV and combined AVTG. Overall, sensitivity, specificity, and accuracy of [18F]FDG PET/CT were 97, 73, and 90%, respectively. In 22 patients with suspected very early and early postsurgical infections, the two imaging modalities were concordant in 17 cases [10 true positive (TP) and 7 true negative (TN)]. [18F]FDG PET/CT presented a higher sensitivity than 99mTc-HMPAO-WBC scan. 99mTc-HMPAO-WBC scan correctly classified as negative three false-positive (FP) PET/CT findings. Conclusion: Our findings supported the use of 99mTc-HMPAO-WBC SPECT/CT and [18F]FDG PET/CT in patients with suspicion infection after the Bentall procedure early in the course of the disease onset to confirm the diagnosis and provide a comprehensive assessment of disease burden through the proposed criteria.

Cardiac molecular pathways influenced by doxorubicin treatment in mice.

Doxorubicin (DOX) is a potent chemotherapeutic with distinct cardiotoxic properties. Understanding the underlying cardiotoxic mechanisms on a molecular level would enable the early detection of cardiotoxicity and implementation of prophylactic treatment. Our goal was to map the patterns of different radiopharmaceuticals as surrogate markers of specific metabolic pathways induced by chemotherapy. Therefore, cardiac distribution of 99mTc-sestamibi, 99mTc-Annexin V, 99mTc-glucaric acid and [18F]FDG and cardiac expression of Bcl-2, caspase-3 and -8, TUNEL, HIF-1α, and p53 were assessed in response to DOX exposure in mice. A total of 80 mice (64 treated, 16 controls) were evaluated. All radiopharmaceuticals showed significantly increased uptake compared to controls, with peak cardiac uptake after one (99mTc-Annexin V), two (99mTc-sestamibi), three ([18F]FDG), or four (99mTc-glucaric acid) cycles of DOX. Strong correlations (p < 0.01) were observed between 99mTc-Annexin V, caspase 3 and 8, and TUNEL, and between [18F]FDG and HIF-1α. This suggests that the cardiac DOX response starts with apoptosis at low exposure levels, as indicated by 99mTc-Annexin V and histological apoptosis markers. Late process membrane disintegration can possibly be detected by 99mTc-sestamibi and 99mTc-glucaric acid. [18F]FDG signifies an early adaptive response to DOX, which can be further exploited clinically in the near future.

The "3M" Approach to Cardiovascular Infections: Multimodality, Multitracers, and Multidisciplinary.

Cardiovascular infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient management, as early treatment improves the prognosis. The diagnosis cannot be made on the basis of a single symptom, sign, or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data, and imaging data. The application of multimodality imaging, including molecular imaging techniques, has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this review, we describe data supporting the use of a Multimodality, Multitracer, and Multidisciplinary approach (the 3M approach) to cardiovascular infections. In particular, the role of white blood cell SPECT/CT and [18F]FDG PET/CT in most prevalent and clinically relevant cardiovascular infections will be discussed. In addition, the needs of advanced hybrid equipment, dedicated imaging acquisition protocols, specific expertise for image reading, and interpretation in this field are discussed, emphasizing the need for a specific reference framework within a Cardiovascular Multidisciplinary Team Approach to select the best test or combination of tests for each specific clinical situation.

Current Status of Molecular Imaging in Infections.

There is an increased need to find non-invasive tools for early diagnosis and follow-up of infections. Nuclear medicine techniques may be used to diagnose, localize and evaluate the severity and the extent of infections before the occurrence of anatomical abnormalities. This review focuses on different approaches based on radiolabelled cells, peptides and antibodies or [18F]FDG to image infective diseases in agreement with what is being jointly evaluated by the European Association of Nuclear Medicine (EANM). This is particularly relevant, since the EANM has strated a wide program of collaboration with other European clinical societies to define common diagnostic flow-charts in many of these infective diseases. It emerges the role of radiolabelled WBC by SPECT/CT for prosthetic joint infections and of FDG by PET/CT for spondylodiscitis. Comparable values of accuracy have been described for WBC and FDG in the diagnosis of vascular fgraft infections, diabetic gfoot, endocarditis and peripheral bone osteomyelitis, with some exceptions.

Miniaturized Radiochemical Purity Testing for 99mTc-HMPAO, 99mTc-HMDP, and 99mTc-Tetrofosmin.

Quick methods are functional in clinical practice to ensure the fastest availability of radiopharmaceuticals. For this purpose, we investigated the radiochemical purity of the widely used 99mTc-hydroxymethylene diphosphonate, 99mTc-hexamethylpropyleneamine oxime, and 99mTc-tetrofosmin by reducing time as compared with the manufacturer's method. Methods: We applied a miniaturized chromatographic method with a reduced strip development from 18 cm to 9 cm for all 3 radiopharmaceuticals. The specific support medium and solvent system of the manufacturer's methods was kept unchanged for 99mTc-hydroxymethylene diphosphonate and 99mTc-tetrofosmin, whereas for 99mTc-hexamethylpropyleneamine oxime the instant thin-layer chromatography (ITLC) polysilicic gel (silicic acid [SA]) was replaced with a monosilicic gel (silicic gel [SG]) in the chromatographic system that uses methyl ethyl ketone as solvent. The method was applied and compared with the routine ITLC insert method in a total of 30 batches for each radiopharmaceutical. The precision of repeated tests was determined by comparison with the results of 10 replications on the same batch. Small volumes of concentrated 99mTcO4-, and 99mTc-albumin nanocolloid were used to produce potential radiochemical impurities. Correlation between the quick methods and the insert methods was analyzed using a nonparametric 2-tailed test and a 2 × 2 contingency table with the associated Fisher exact test to evaluate sensitivity and specificity. A receiver-operating-characteristic analysis was performed to evaluate the best cutoff. Results: The percentage radiochemical purity of the quick methods agreed with the standard chromatography procedures. We found that 99mTcO4 and colloidal impurities are not the only common radiochemical impurities with 99mTc-tetrofosmin, and shortening of the ITLC strip with respect to the manufacturer's method will worsen system resolution and may produce inaccuracy. Conclusion: The miniaturized methods we described represent a fast and reliable alternative for 99mTc-exametazime and 99mTc-oxidronate quality control, with the upper cutoff for acceptable radiochemical purity values being 84% and 95%, respectively. For 99mTc-tetrofosmin radiochemical purity testing, a longer strip as described in the standard method is warranted.

ED-B fibronectin expression is a marker of epithelial-mesenchymal transition in translational oncology.

Fibronectin is a component of the extracellular matrix that links collagen fibers to integrins on the cell's surface. The splicing isoforms, containing the ED-B domain, are not expressed in adult tissues but only in tumor stroma or during embryonic development. Fibroblasts and endothelial cells express ED-B fibronectin during angiogenesis. Also cancer cells can synthetize ED-B fibronectin, but its function in tumor growth needs to be further elucidated.We evaluated the expression of ED-B fibronectin in prostate cancer cell lines: PC3 and DU145. Using TGF-ß, we induced epithelial to mesenchymal transition in culture and observed an increase of ED-B fibronectin expression. Thereafter, we evaluated the expression of ED-B fibronectin in multipotent mesangiogenic progenitor cells, and in mesenchymal stromal cells. The expression of ED-B fibronectin was much higher in mesenchymal than prostate cancer cells even after the epithelial to mesenchymal transition.Epithelial to mesenchymal transition is a key step for tumor progression contributing to the metastatic spread. Therefore, circulating cancer cells could seed into the metastatic niche taking advantage from the ED-B fibronectin that secrete their own.

Detection of a second malignancy in prostate cancer patients by using [(18)F]Choline PET/CT: a case series.

BACKGROUND: The role of radiolabeled choline (Cho) in patients with biochemical recurrence after radical treatment for prostate cancer (PCa) is well established. Its widespread clinical use has prompted the depiction of incidentalomas, unusual sites of metastatic lesions, as well as false positive and negative cases. We reported a series of patients affected by biochemical recurrence of PCa imaged by [(18)F]Cho positron emission tomography/computed tomography (PET/CT) which resulted suspected for a second malignancy. CASE PRESENTATION: [(18)F]Cho PET/CT was performed in patients with biochemical PCa recurrence. From an internal clinical database we identified patients in which PET/CT resulted suspected for a second malignancy. A second malignancy was suspected in presence of "unusual" site of [(18)F]Cho uptake not consistent with clinical-instrumental history. Histology was used as reference standard for final diagnosis. Seven PCa patients (76 years, 71-84 years) with the suspicion of a second tumor based on [(18)F]Cho PET/CT findings were identified. Mean value of PSA at the time of [(18)F]Cho PET/CT was 2,37 ng/mL. The median time between PCa diagnosis and PET/CT was 6 years (range 0-14 years). In two cases history of a second malignancy (lung cancer and cutaneous basocellular carcinoma) was known (diagnosed 12 and 6 years after PCa, respectively). PET/CT identified 13 sites of [(18)F]Cho uptake (lung = 5, lymph node = 7, bone = 1). Final diagnosis was consistent with lung cancer in 5/7 cases (first diagnosis = 4/5, recurrence = 1/5), colorectal cancer and nodal metastases from melanoma in 1 case each. CONCLUSIONS: Although the clinical usefulness of Cho PET/CT for detecting cancer lesions other than prostate origin is known, for those patients who undergo this examination according to indication, the diagnosis of a second tumor has a significant impact on their therapeutic management.

Long-Term PSA Control with Repeated Stereotactic Body Radiotherapy in a Patient with Oligometastatic Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is one of the most common malignancies and main causes of cancer death in Western countries. In the presence of metastatic disease, systemic treatment remains the main clinical option. However, since the introduction of highly sensitive imaging techniques, a new clinical 'entity' of metastatic patients with a limited number of lesions has been defined: oligometastatic patients. In this patient group, the use of stereotactic body radiotherapy (SBRT) or other local therapies against all active sites of disease revealed by 18F-choline positron emission tomography/computed tomography (PET/CT) could achieve sufficient prostate-specific antigen (PSA) control. However, a clear benefit of this procedure in terms of significant endpoints is yet to be demonstrated. This case report describes our experience with treating a castration-resistant PCa patient with 18F-choline PET/CT-guided SBRT. Because of the occurrence of 5 metachronous lesions over 4 years, the pattern of recurrence was defined by the local multidisciplinary team as oligometastatic disease, and the patient was treated with 5 courses of SBRT which yielded good PSA control. He started systemic therapy with abiraterone acetate almost 5 years after the diagnosis of recurrent PCa.

Brief report on the use of radiolabeled somatostatin analogs for the diagnosis and treatment of metastatic small-cell lung cancer patients.

INTRODUCTION: The demonstration of type 2 somatostatin receptors (SSTRs) in small-cell lung cancer (SCLC) represents the rationale for the use of positron emission tomography/computed tomography (PET/CT) to determine SSTR expression, and select patients suitable for peptide radioreceptor radionuclide therapy (PRRT) in extensive-disease stage (ED) SCLC. METHODS: We evaluated 24 ED-SCLC patients with radiolabeled SST-analog PET/CT. Lesions at PET/CT scan were semiquantitatively scored (from 0 to 3+) and compared with contrast-enhanced CT findings. Patients scored as 3+ were admitted to PRRT after dosimetric evaluation. Average injected activity/cycle was 2.6 GBq (yttrium-PRRT) or 6.0 GBq (lutetium-PRRT). PRRT efficacy was clinically and radiologically assessed. RESULTS: PET/CT was negative in four of 24 patients, whereas in the remaining 20 cases uptake was scored as 1+ in seven of 20, 2+ in one of 20, and 3+ in 12 of 20. Primary tumor lesions showed uptake in 16 of 24 patients. Uptake in metastatic lesions was observed in four of four adrenals, two of five brain, 12 of 16 bone, three of eight liver, and 17 of 20 lymph node lesions. Of the 12 patients eligible for PRRT, 11 were eventually treated and four of 11 patients received multiple PRRT administrations. Dosimetry resulted in a BED for kidney of 7.5 Gy (range, 4-21); bone marrow provisional dosage was 0.43 Gy (range, 0.1-1.7). Hematological PRRT toxicity occurred in three of 11 patients. No clinical or objective responses were observed with disease progression occurring approximately 48 days (range, 9-32) after PRRT. CONCLUSION: Radiolabeled SST-analog PET/CT demonstrated enhanced SSTR expression in 50% of cases. Nevertheless, PRRT in ED-SCLC was ineffective, suggesting the need to anticipate or combine PRRT in a multimodality approach.