PET/CT Imaging of Infectious Diseases: Overview of Novel Radiopharmaceuticals.

Infectious diseases represent one of the most common causes of hospital admission worldwide. The diagnostic work-up requires a complex clinical approach, including laboratory data, CT and MRI, other imaging tools, and microbiologic cultures. PET/CT with 18F-FDG can support the clinical diagnosis, allowing visualization of increased glucose metabolism in activated macrophages and monocytes; this tracer presents limits in differentiating between aseptic inflammation and infection. Novel PET radiopharmaceuticals have been developed to overcome these limits; 11C/18F-labeled bacterial agents, several 68Ga-labeled molecules, and white blood cells labeled with 18F-FDG are emerging PET tracers under study, showing interesting preliminary results. The best choice among these tracers can be unclear. This overview aims to discuss the most common diagnostic applications of 18F-FDG PET/CT in infectious diseases and, as a counterpoint, to describe and debate the advantages and peculiarities of the latest PET radiopharmaceuticals in the field of infectious diseases, which will probably improve the diagnosis and prognostic stratification of patients with active infectious diseases.

Magnetic resonance-guided focused ultrasound versus percutaneous thermal ablation in local control of bone oligometastases: a systematic review and meta-analysis.

BACKGROUND: The percutaneous thermal ablation techniques (pTA) are radiofrequency ablation, cryoablation, and microwave ablation, suitable for the treatment of bone oligometastases. Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive ablation technique. OBJECTIVES: To compare the effectiveness and safety of MRgFUS and pTA for treating bone oligometastases and their complications. METHODS: Studies were selected with a PICO/PRISMA protocol: pTA or MRgFUS in patients with bone oligometastases; non-exclusive curative treatment. Exclusion criteria were: primary bone tumor; concurrent radiation therapy; palliative therapy; and absence of imaging at follow-up. PubMed, BioMed Central, and Scopus were searched. The modified Newcastle-Ottawa Scale assessed articles quality. For each treatment (pTA and MRgFUS), we conducted two separate random-effects meta-analyses to estimate the pooled effectiveness and safety. The effectiveness was assessed by combining the proportions of treated lesions achieving local tumor control (LTC); the safety by combining the complications rates of treated patients. Meta-regression analyses were performed to identify any outcome predictor. RESULTS: A total of 24 articles were included. Pooled LTC rate for MRgFUS was 84% (N = 7, 95% CI 66-97%, I2 = 74.7%) compared to 65% of pTA (N = 17, 95% CI 51-78%, I2 = 89.3%). Pooled complications rate was similar, respectively, 13% (95% CI 1-32%, I2 = 81.0%) for MRgFUS and 12% (95% CI 8-18%, I2 = 39.9%) for pTA, but major complications were recorded with pTA only. The meta-regression analyses, including technique type, study design, tumor, and follow-up, found no significant predictors. DISCUSSION: The effectiveness and safety of the two techniques were found comparable, even though MRgFUS is a noninvasive treatment that did not cause any major complication. Limited data availability on MRgFUS and the lack of direct comparisons with pTA may affect these findings. CONCLUSIONS: MRgFUS can be a valid, safe, and noninvasive treatment for bone oligometastases. Direct comparison studies are needed to confirm its promising benefits.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging.

We observed several patients presenting 2-[18F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [18F]Choline PET/CT. The aim of our study was to describe this source of false positive cases. All patients examined by PET/CT were included in the study. Data concerning patient anamnesis, laterality, and time interval from recent COVID-19 vaccination were recorded. SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination. Among 712 PET/CT scans with 2-[18F]FDG, 104 were submitted to vaccination; 89/104 patients (85%) presented axillary and/or deltoid tracer uptake, related to recent COVID-19 vaccine administration (median from injection: 11 days). The mean SUVmax of these findings was 2.1 (range 1.6-3.3). Among 89 patients with false positive axillary uptake, 36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas, prior to the scan: 6/36 patients with lymph node metastases showed no response to therapy or progression disease. The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8. Only 1/31 prostate cancer patients examined by [18F]Choline PET/CT showed post-vaccine axillary lymph node uptake. These findings were not recorded at PET/CT scans with [18F]-6-FDOPA, [68Ga]Ga-DOTATOC, and [18F]-fluoride. Following COVID-19 mass vaccination, a significant percentage of patients examined by 2-[18F]FDG PET/CT presents axillary, reactive lymph node uptake. Anamnesis, low-dose CT, and ultrasonography facilitated correct diagnosis. Semi-quantitative assessment supported the visual analysis of PET/CT data; SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes. [18F]Choline uptake in reactive lymph node after vaccination was confirmed. After the COVID-19 pandemic, nuclear physicians need to take these potential false positive cases into account in daily clinical practice.

Positron Emission Tomography Molecular Imaging of the Major Neurodegenerative Disorders: Overview and Pictorial Essay, from a Nuclear Medicine Center's Perspective.

Computed tomography (CT) and magnetic resonance imaging (MRI) provide key structural information on brain pathophysiology. Positron emission tomography (PET) measures metabolism in the living brain; it plays an important role in molecular neuroimaging and is rapidly expanding its field of application to the study of neurodegenerative diseases. Different PET radiopharmaceuticals allow in vivo characterization and quantization of biological processes at the molecular and cellular levels, from which many neurodegenerative diseases develop. In addition, hybrid imaging tools such as PET/CT and PET/MRI support the utility of PET, enabling the anatomical mapping of functional data. In this overview, we describe the most commonly used PET tracers in the diagnostic work-up of patients with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. We also briefly discuss the pathophysiological processes of tracer uptake in the brain, detailing their specific cellular pathways in clinical cases. This overview is limited to imaging agents already applied in human subjects, with particular emphasis on those tracers used in our department.

PET Molecular Imaging: Old Habits Do Not Die, They Only Evolve into New Applications.

The first studies on human applications of radioisotopes for the in vivo targeting of pathophysiological processes began in the late 1930s in Western Europe and the USA with 99mTc [...].

Peptide Receptor Radionuclide Therapy and Primary Brain Tumors: An Overview.

Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease.

131I Uptake in Bronchiectasis Detected by Single Photon Emission Computed Tomography/Computed Tomography during Follow-up of Thyroid Cancer.

During follow-up of thyroid cancer, 131I whole-body scan showed intense tracer uptake in the right hemithorax of a patient previously submitted to thyroidectomy and radioiodine therapy for differentiated thyroid cancer. Thyroglobulin was undetectable at the time of the scan. Single-photon emission computed tomography/computed tomography (SPECT/CT) of the thorax correctly identified widespread bronchiectasis 131I-avid in the middle lobe of the right lung. After bronchoalveolar lavage, a bronchial specimen was positive for Mycobacterium avium infection. Hybrid imaging with SPECT/CT allowed to correctly identify a false-positive case of 131I uptake due to inflammation in a single diagnostic session, minimizing patient discomfort or misdiagnoses.

68Ga/64Cu PSMA Bio-Distribution in Prostate Cancer Patients: Potential Pitfalls for Different Tracers.

BACKGROUND: 68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases. METHODS: We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented. RESULT: Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis. DISCUSSION: Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice. CONCLUSION: The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

Overall survival and progression-free survival in patients with primary brain tumors after treatment: is the outcome of [18F] FDOPA PET a prognostic factor in these patients?

AIM: To investigate the progression-free survival (PFS) and the overall survival (OS) in a population affected by primary brain tumors (PBT) evaluated by [18F]-L-dihydroxyphenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS: 133 subjects with PBT (65 women and 68 men, mean age 45 ± 10 years old) underwent 18F FDOPA PET/CT after treatment. Of them, 68 (51.2%) were Grade II, 34 (25.5%) were Grade III and 31 (23.3%) were Grade IV. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs. that of the background. Patients have been observed for a mean of 24 months. RESULTS: The outcome of [18F] FDOPA PET/CT scan was significantly related to the OS and PFS in Grade II gliomas. In Grade II PBT, the OS proportions at 24 months were 100% in subjects with a negative PET/CT scan and 82% in those with a positive scan. Gehan-Breslow-Wilcoxon test showed a significant difference in the OS curves (P = 0.03) and the hazard-ratio was equal to 5.1 (95% CI of ratio 1.1-23.88). As for PFS, the proportion at 24 months was 90% in subjects with a negative PET/CT scan and 58% in those with a positive scan. Gehan-Breslow-Wilcoxon test showed a significant difference in the OS curves (P = 0.007) and the hazard-ratio was equal to 4.1 (95% CI of ratio 1.3-8). We did not find any significant relationship between PET outcome and OS and PFS in Grade III and IV PBT. CONCLUSIONS: A positive [18F] FDOPA PET/CT scan is related to a poor OS and PFS in subjects with low-grade PBT. This imaging modality could be considered as a prognostic factor in these subjects.

Situs Inversus Totalis and Cholangiocarcinoma of the Gallbladder Detected by 18F-FDG PET/CT.

A 72-year-old woman was examined by F-FDG PET/CT, showing pathologic tracer uptake in the gallbladder. PET/CT also depicted condition of situs inversus totalis, with dextrocardia, liver on the left side and spleen on the right side of the body. These findings were essential to plan and develop laparoscopic cholecystectomy, which diagnosed cholangiocarcinoma. The recognition of anatomical variants and abnormalities by means of hybrid PET/CT imaging is essential in order to plan the best therapeutic approach.

Molecular imaging of brain tumors with radiolabeled choline PET.

Several positron emission tomography (PET) radiopharmaceuticals have been emerged in the last decade as feasible in the management of brain lesions, due to the low performance in this field of the 18F-fluoro-deoxyglucose (18F-FDG), for its high physiological gradient of distribution in the brain. Beyond its usefulness in prostate cancer imaging, the radiolabeled choline is becoming a promising tool in diagnosing benign and malignant lesions of the brain, due to a very low rate of distribution in normal white and grey matters. The aim of our review was to assess the real impact of the radiolabeled choline PET/CT in the management of brain benign lesions, brain tumors, and metastases. Furthermore, emphasis was given to the comparison between the radiolabeled choline and the other radiopharmaceuticals in this field. A literature review was performed. The radiolabeled choline is useful in the management of patients with suspected brain tumor relapse, especially in association with magnetic resonance imaging (MRI), with caution regarding its intrinsic characteristic of non-tumor-specific tracer. For the same reason, it is not useful in the early evaluation of brain lesions. Similar results are reported for other radiopharmaceuticals. The inclusion of the head in the whole-body scans for somatic tumors is necessary to ensure metastases in the brain or choline-avid benign lesions.

The role of self-expandable metallic stents as "bridge to surgery" for the treatment of acute malignant colorectal obstruction. Our experience.

INTRODUCTION: Despite the widespread use of screening programs, the colorectal cancer occurs in 7-29% of cases with a bowel obstruction, needing an immediate decompression treatment by emergency surgery; unfortunately, the emergency surgery is characterized by high morbidity and mortality rates. The endoscopic placement of self-expandable metallic stents can be a useful alternative, allowing to decompress the acute obstruction in a short time, in order to correct dehydration, electrolytic imbalance and to improve the overall clinical conditions prior to adequately plan the intervention of elective surgery. AIM: The objective of our study was to evaluate the clinical success and potential complications related to the stent placement as "bridge to surgery". MATERIALS AND METHODS: Twenty-four patients with acute intestinal obstruction due to colorectal cancer were retrospectively observed in our Surgery Unit. They were selected only patients in whom technical success, defined as the correct placement of the stent, was recorded. All patients underwent a preoperative abdominal X-rays and whole body contrast- enhanced Computed Tomography (ceCT). Furthermore, an intraoperative fluoroscopy was also performed to obtain a better anatomical depiction of the lesions. The sites of obstruction were in the left colon (n=13) and in the proximal rectal tract (n=11). Covered and uncovered stents were placed respectively in 12 and 12 patients. The Over The Wire (OTW) technique has been used in 11 patients while the Through The Scope (TTS) technique in 13 subjects. All patients were brought to elective surgery in 5-10 days. The clinical success was defined as the resumption of normal bowel function within 48-72 hours and the absence of complications. RESULTS: Technical success was documented in 24 patients (100%). Clinical success was recorded in 17 patients (70.8%) while, in 7 patients, as treatment complications were recorded: 2 stent migrations (8.3%), 2 cases with tenesmus (8.3%), 2 bleeding (8.3%), 2 cases of abdominal pain (8.3%) and 1 case of perforation (4.2%), were recorded. CONCLUSION: In our series we found that placing self-expandable metallic stents, considered as "bridge to surgery", was a useful technique in the resolution of acute malignant colorectal obstructions, with high success rate and low rate of complications. KEY WORDS: Colorectal cancer, Clinical success, Large bowel obstruction, Radiology, Self-expanding metallic stent, Stenting, Surgery.

Ictal 18F-FDG PET/MRI in a Patient With Cortical Heterotopia and Focal Epilepsy.

A 19-year-old man with epilepsy underwent ictal F-FDG PET/MRI, showing a 5 mm heterotopic nodule in the periventricular white matter, adjacent to the frontal horn of the left lateral ventricle (SUVmax, 5.5; glucidic cerebral metabolic rate, 0.317 µmol/mL). A repeated F-FDG PET/MRI, during seizure freedom, showed, at visual analysis, subtle decrease of the nodule metabolism. SUVmax and glucidic cerebral metabolic rate were clearly reduced to 3.7 and 0.226, respectively. Ictal F-FDG PET/MRI could be useful in epilepsy because of the added value of SUVmax and cerebral metabolic rate of glucose analysis to understand the relationship between heterotopy and epilepsy.

The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells.

BACKGROUND/AIMS: The importance of copper in the metabolism of cancer cells has been widely studied in the last 20 years and a clear-cut association between copper levels and cancer deregulation has been established. Copper-64, emitting positrons and ß-radiations, is indicated for the labeling of a large number of molecules suitable for radionuclide imaging as well as radionuclide therapy. Glioblastoma multiforme (GBM) is the CNS tumor with the worse prognosis, characterized by high number of recurrences and strong resistance to chemo-radio therapy, strongly affecting patients survival. We have recently discovered and studied the small molecule SI113, as inhibitor of SGK1, a serine/threonine protein kinase, that affects several neoplastic phenotypes and signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation, perturbs cell cycle progression and restores chemo-radio sensibility by modulating SGK1-related substrates. In the present paper we aim to characterize the combined effects of 64CuCl2 and SI113 on human GBM cell lines with variable p53 expression. METHODS: Cell viability, cell death and stress/authopagic related pathways were then analyzed by FACS and WB-based assays, after exposure to SI113 and/or 64CuCl2. RESULTS: We demonstrate here, that i) 64CuCl2 is able to induce a time and dose dependent modulation of cell viability (with different IC50 values) in highly malignant gliomas and that the co-treatment with SI113 leads to ii) additive/synergistic effects in terms of cell death; iii) enhancement of the effects of ionizing radiations, probably by a TRC1 modulation; iv) modulation of the autophagic response. CONCLUSIONS: Evidence reported here underlines the therapeutic potential of the combined treatment with SI113 and 64CuCl2 in GBM cells.

PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

INTRODUCTION: The 11C/18F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11C/18F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18F-choline bio-distribution in the female body. METHODS: We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18F-choline PET/CT in 5 female patients. RESULTS: 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. CONCLUSIONS: The accurate knowledge of 18F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18F-choline uptake in the exocrine glands. ADVANCES IN KNOWLEDGE: Our results confirm the possibility of 18F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. IMPLICATIONS FOR PATIENT CARE: The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a better patient quality of life.

Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging of Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.

OBJECTIVE: To assess the diagnostic accuracy of 64Copper prostate-specific membrane antigen (64Cu-PSMA) positron emission tomography/computed tomography (PET/CT) in the primary lymph node (LN) staging of a selected cohort of intermediate- to high-risk prostate cancer (PCa) patients. MATERIALS AND METHODS: An observational prospective study was performed in 23 patients with intermediate- to high-risk PCa, who underwent 64Cu-PSMA PET/CT for local and lymph nodal staging before laparoscopic radical prostatectomy with an extended pelvic LN dissection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for LN status of 64Cu-PSMA PET/CT were calculated using the final pathological findings as reference. Furthermore, we evaluated the correlation of intraprostatic tumor extent and grading with 64Cu-PSMA intraprostatic distribution. RESULTS: Pathological analysis of LN involvement in 413 LNs harvested from our study cohort identified a total of 22 LN metastases in 8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient analysis showed that 64Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of 93.7%, considering the maximum standardized uptake value (SUVmax) at 4 hours as our reference. Receiver operating characteristic curve was characterized by an area under the curve of 0.938. A significant positive association was observed between SUVmax at 4 hours with Gleason score, index, and cumulative tumor volume. CONCLUSION: In our intermediate- to high-risk PCa patients study cohort, we showed the high diagnostic accuracy of 64Cu-PSMA PET/CT for primary LN staging before radical prostatectomy.

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients.

PURPOSE: F-DOPA PET/CT is potentially helpful in the management of patients with low-grade brain tumors, movement disorders, and somatic neuroendocrine tumors. We describe the whole-body physiological distribution of F-DOPA uptake. PATIENTS AND METHODS: We examined 215 patients with F-DOPA PET/CT. Among these, 161 had brain scans and 54 had whole-body scans. RESULTS: Physiological distribution was negligible in the brain, with the exception of basal ganglia, whereas greatest activity was noted in the liver, pancreas, other exocrine glands, and the urinary system. Incidental tracer uptake sites were identified in 5.5% of patients. Some of these findings were due to inflammation, whereas in most cases, uptake was seen in benign tumors of the brain or in the endocrine or exocrine glands. CONCLUSIONS: F-DOPA uptake may be seen in inflammatory tissue or benign tumors. Correlations with history, physical examination, laboratory examination, CT, MRI, and histology are necessary for optimal diagnosis.

18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas.

A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas.