Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand?

INTRODUCTION: The term theragnostic refers to the combination of a predictive imaging biomarker with a therapeutic agent. The promising application of prostate-specific membrane antigen (PSMA)-based radiopharmaceuticals in the imaging and treatment of prostate cancer (PCa) patients opens the way to investigate a possible role of PSMA-based radiopharmaceuticals in cancers beyond the prostate. Therefore, the aim of this review was to evaluate the role of 177Lu-PSMA radioligand therapy (RLT) in malignancies other than prostate cancer by evaluating preclinical, clinical studies, and ongoing clinical trials. METHODS: An extensive literature search was performed in three different databases using different combinations of the following terms: "Lu-PSMA", "177Lu-PSMA", "preclinical", "mouse", "salivary gland cancer", "breast cancer", "glioblastoma", "solid tumour", "renal cell carcinoma", "HCC", "thyroid", "salivary", "radioligand therapy", and "lutetium-177". The search had no beginning date limit and was updated to April 2024. Only articles written in English were included in this review. RESULTS: A total of four preclinical studies were selected (breast cancer model n = 3/4). PSMA-RLT significantly reduced cell viability and had anti-angiogenic effects, especially under hypoxic conditions, which increase PSMA binding and uptake. Considering the clinical studies (n = 8), the complexity of evaluating PSMA-RLT in cancers other than prostate cancer was clearly revealed, since in most of the presented cases a sufficient tumour radiation dose was not achieved. However, encouraging results can be found in some types of diseases, such as thyroid cancer. Some clinical trials are still ongoing, and results from prospective larger cohorts of patients are awaited. CONCLUSIONS: The need for larger patient cohorts and more RLT cycles administered underscores the need for further comprehensive studies. Given the very preliminary results of both preclinical and clinical studies, ongoing clinical trials in the near future may provide stronger evidence of both the safety and therapeutic efficacy of PSMA-RLT in malignancies other than prostate cancer.

Cardiac sympathetic activity and lethal arrhythmic events: insight into bell-shaped relationship between 123I-meta-iodobenzylguanidine activity and event rates.

BACKGROUND: 123I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts. RESULTS: We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I. CONCLUSIONS: The relationship between cardiac 123I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.

Extraosseous distribution of 99mTc-diphosphonates during bone scintigraphy: review of the literature with case series presentation.

PURPOSE: Technetium-99m (99mTc)-diphosphonates represent the most common radiopharmaceutical used for bone scintigraphy. Even if the uptake in bone tissue has been widely explored, atypical uptake could be seen in soft tissue malignancies during bone scintigraphy. Increased vascularization and endothelium permeability represent front-row players in the biodistribution of the tracer, albeit other causes have been identified such as trauma, necrosis, the presence of calcification in metastasis, the pH of the tissue and consequently the type of ion concentration. CONCLUSION: The aim of this paper is to summarize the state of art of atypical soft tissue uptake seen in cancer tissues. The research was conducted on PubMed. The analysis of the literature suggests that calcium metabolism and ionic saturation have a pivotal role in the biodistribution of bone tracers. This phenomenon ranks in a complex scenario that includes carcinogenesis and cancer environment aspects. We also report two cases in our Institution in which atypical uptake in cancer tissues was observed.

18F-FDG PET/CT technology for the assessment of brown adipose tissue: an updated review.

INTRODUCTION: This review provides an update of 18 F-fluorodeoxyglucose ([18F] FDG) for Brown adipose tissue (BAT) activity quantification, whose role is not completely understood. AREAS COVERED: We conducted an unstructured search of the literature for any studies employing the [18F] FDG PET in BAT assessment. We explored BAT quantification both in healthy individuals and in different pathologies, after cold exposure and as a metabolic biomarker. The assessment of possible BAT modulators by using [18F] FDG PET is shown. Further PET tracers and novel developments for BAT assessments are also described. EXPERT OPINION: Further PET tracers and imaging modalities are under investigation, but the [18F] FDG PET is currently the method of choice for the evaluation of BAT and further multicentric trials are needed for a better understanding of the BAT physiopathology, also after cold stimuli. The modulation of BAT activity, assessed by [18F] FDG PET imaging, seems a promising tool for the management of conditions such as obesity and type 2 diabetes. Moreover, an interesting possible correlation of BAT activation with prognostic [18F] FDG PET indices in cancer patients should be assessed with further multicentric trials.

The added value of lung perfusion scintigraphy semiquantitative measures in post-COVID patients with persistent dyspnea without pulmonary embolism.

BACKGROUND: Persistent dyspnea is frequent in post-COVID patients, even in the absence of pulmonary embolism (PE). In this scenario, the role of lung perfusion scintigraphy is unclear. The present study correlated scintigraphy-based semiquantitative perfusion parameters with chest high-resolution computed tomography (hrCT) volumetric indexes and clinical data in post-COVID patients with persistent dyspnea. RESEARCH DESIGN AND METHODS: Sixty patients (30 post-COVID and 30 not previously affected by COVID-19) with persistent dyspnea submitted to lung perfusion scintigraphy and hrCT were retrospectively recruited. Perfusion rates of the pulmonary fields and hrCT-based normalized inflated, emphysematous, infiltrated, collapsed, and vascular lung volumes were calculated. Inflammatory and coagulation biomarkers were collected. PE at imaging was an exclusion criterion. RESULTS: Compared to controls, reduced perfusion rates of the lower pulmonary fields and higher perfusion rates of the middle ones were observed in post-COVID patients, while hrCT findings were superimposable between the two groups. Perfusion rates of lower pulmonary fields were significantly associated only with abnormal lung volumes at hrCT. CONCLUSIONS: In post-COVID dyspnea without PE, lung perfusion scintigraphy may reveal a pulmonary involvement not detectable by hrCT. Post-COVID patients may show decreased perfusion rates of lower pulmonary fields in the presence of normal vascular density and markers of inflammation/coagulation.

Radio-Guided Lung Surgery: A Feasible Approach for a Cancer Precision Medicine.

BACKGROUND: Radio-guided surgery is a reliable approach used for localizing ground-glass opacities, lung nodules, and metastatic lymph nodes. Lung nodules, lymph node metastatic involvement, and ground-glass opacities often represent a challenge for surgical management and clinical work-up. METHODS: PubMed research was conducted from January 1997 to June 2023 using the keywords "radioguided surgery and lung cancer". RESULTS: Different studies were conducted with different tracers: technetium-99m-albumin macroaggregates, cyanoacrylate combined to technetium-99m-sulfur colloid, indium-111-pentetreotide, and fluorine-18-deoxyglucose. A study proposed naphthalocyanine radio-labeled with copper-64. Radio-guided surgery has been demonstrated to be a reliable approach in localizing a lesion, and has a low radiological burden for personnel exposure and low morbidity. The lack of necessity to conduct radio-guided surgery under fluoroscopy or echography makes this radio-guided surgery an easy way of performing precise surgical procedures. CONCLUSIONS: Radio-guided surgery is a feasible approach useful for the intraoperative localization of ground-glass opacities, lung nodules, and metastatic lymph nodes. It is a valid alternative to the existing approaches due to its low cost, associated low morbidity, the possibility to perform the procedure after several hours, the low radiation dose applied, and the small amount of time that is required to perform it.

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. METHODS: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. RESULTS: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). CONCLUSIONS: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.

Sex differences in 123I-mIBG scintigraphy imaging techniques in patients with heart failure.

BACKGROUND: 123I-mIBG-scintigraphy could be a useful stratifying tool for patients with heart failure (HF). The purpose of this retrospective study is to evaluate whether there are differences between men and women with HF in terms of the prediction of cardiac arrhythmic events (AE). RESEARCH AND METHODS: A total of 306 patients, before implantable-cardioverter-defibrillator (ICD) implantation, were evaluated. They underwent 123I-mIBG-scintigraphy and an evaluation of the results was performed after 85 months of follow-up. Early and late planar and SPECT cardiac images were acquired. Heart-to-mediastinum ratio (HM) for planar images and the sum of the segmental scores (SS) for SPECT were calculated. RESULTS: In the general population, age, early SS (ESS), late SS (LSS), and ejection fraction (EF) were statistically significant for the prediction of AE at Cox regression, while early and late HM (eHM,lHM) were not significative for the prediction of AE. Population was divided into females and males and univariate analysis was conducted separately for the two cohorts: no significant variables for prediction of AE were found in females. For males, ESS, LSS, EF, and late HM were statistically significant predictors of AE. The overall survival was similar in males and females, but the risk of AE is lower in males than in females. CONCLUSIONS: 123I-mIBG represents a more effective tool for the prediction of AE in male patients than in women.

Medication and ECG Patterns That May Hinder SPECT Myocardial Perfusion Scans.

Coronary artery disease (CAD) is the leading cause of death followed by cancer, in men and women. With risk factors being endemic and the increasing costs of healthcare for management and treatment, myocardial perfusion imaging (MPI) finds a central role in risk stratification and prognosis for CAD patients, but it comes with its limitations in that the referring clinician and managing team must be aware of and use at their advantage. This narrative review examines the utility of myocardial perfusion scans in the diagnosis and management of patients with ECG alterations such as atrioventricular block (AVB), and medications including calcium channel blockers (CCB), beta blockers (BB), and nitroglycerin which may impact the interpretation of the exam. The review analyzes the current evidence and provides insights into the limitations, delving into the reasons behind some of the contraindications to MPI.

Novel Theranostic Approaches Targeting CCR4-Receptor, Current Status and Translational Prospectives: A Systematic Review.

BACKGROUND: With the high mortality rate of malignant tumors, there is a need to find novel theranostic approaches to provide an early diagnosis and targeted therapy. The chemokine receptor 4 (CCR4) is highly expressed in various tumors and plays an important role in tumor pathogenesis. This systematic review aims to provide a complete overview on clinical and preclinical applications of the CCR4 receptor as a target for theranostics, using a systematic approach to classify and assemble published studies performed on humans and animals, sorted by field of application and specific tumor. METHODS: A systematic literature search of articles suiting the inclusion criteria was conducted on Pubmed, Scopus, Central, and Web of Science databases, including papers published from January 2006 to November 2022. Eligible studies had to be performed on humans and/or in vivo/in vitro studying CCR4 expression in tumors. The methodological quality was assessed through the Critical Appraisal Skills Programme (CASP) assessing only the studies performed on humans. RESULTS: A total of 17 articles were screened. The articles were assessed for eligibility with the exclusion of 4 articles. Ultimately, 13 articles were selected for the qualitative analysis, and six articles were selected for the critical appraisal skills program. CONCLUSIONS: The development of new radionuclides and radiopharmaceuticals targeting CCR4 show promising results in the theranostics of CCR4 sensible tumors. Although to widen its use in clinical practice, further translation of preclinical to clinical data is needed.

Imaging of Tauopathies with PET Ligands: State of the Art and Future Outlook.

(1) Background: Tauopathies are a group of diseases characterized by the deposition of abnormal tau protein. They are distinguished into 3R, 4R, and 3R/4R tauopathies and also include Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Positron emission tomography (PET) imaging represents a pivotal instrument to guide clinicians. This systematic review aims to summarize the current and novel PET tracers. (2) Methods: Literature research was conducted on Pubmed, Scopus, Medline, Central, and the Web of Science using the query "pet ligands" and "tauopathies". Articles published from January 2018 to 9 February, 2023, were searched. Only studies on the development of novel PET radiotracers for imaging in tauopathies or comparative studies between existing PET tracers were included. (3) Results: A total of 126 articles were found, as follows: 96 were identified from PubMed, 27 from Scopus, one on Central, two on Medline, and zero on the Web of Science. Twenty-four duplicated works were excluded, and 63 articles did not satisfy the inclusion criteria. The remaining 40 articles were included for quality assessment. (4) Conclusions: PET imaging represents a valid instrument capable of helping clinicians in diagnosis, but it is not always perfect in differential diagnosis, even if further investigations on humans for novel promising ligands are needed.

A Systematic Review on Dementia and Translocator Protein (TSPO): When Nuclear Medicine Highlights an Underlying Expression.

BACKGROUND: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging. METHODS: An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation. RESULTS: A total of 50 articles was identified. Twelve papers were selected from the included studies' bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment. CONCLUSION: Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of 18F makes this isotope a preferable choice to 11C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers' effects and increasing the noise ratio in images.

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study.

BACKGROUND/AIM: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. METHODS: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. RESULTS: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12-14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052-1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040-1.068, p < 0.001). CONCLUSIONS: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Evaluation of Bone Scan Index as a Prognostic Tool in Breast Cancer Patients with Bone Metastasis.

BACKGROUND: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy. OBJECTIVE: The aim of this study was to associate BSI with OS in bone metastatic BC patients. METHODS: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account. RESULTS: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924). CONCLUSION: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

Role of Exendin-4 Functional Imaging in Diagnosis of Insulinoma: A Systematic Review.

BACKGROUND: Insulinomas are the most common neuroendocrine neoplasms of the pancreas. Diagnosis is made through patient clinical presentation with hypoglycemia symptoms and imaging, such as EUS, CT, MRI, and functional imaging. Exendin-4 PET/CT (and SPECT/CT) is a new prominent radiotracer developed to image insulinomas. The aim of the study is to evaluate whether exendin-4 imaging is a useful tool in imaging for insulinoma patients when other imaging methods do not reach them. METHODS: MEDLINE research conducted on PubMed, Scopus, and Web of Science gathered a total of 501 papers. Studies that evaluated exendin-4 SPECT and PET in insulinoma patients were screened and assessed through QUADAS-2 for risk of bias and applicability concerns' assessment. Sensitivity, specificity, and accuracy were reported when available. RESULTS: A total of 13 studies were deemed eligible for a QUADAS 2 review. Studies included ranged from 2009 to 2022. The most-used tracer was 68Ga-DOTA-exendin-4 in PET and 111In-DTPA-exendin-4 in SPECT. Exendin-4 labeled with 99mTc was also reported. The QUADAS-2 risk of bias assessment was overall low, with some unclear reports in the reference and index domains. Only two domains were at high risk of bias because of an explicated non-blind imaging review. Applicability concerns for bias were low in all domains. Reported sensitivities ranged from 95% to 100% and specificities from 20% to 100%. CONCLUSIONS: exendin-4 imaging is a sensitive functional imaging tracer in both SPECT and PET applications, especially in suspicion of benign insulinomas located where endoscopic ultrasound cannot reach, being more sensitive than morfostructural imaging.

PET Criteria by Cancer Type from Imaging Interpretation to Treatment Response Assessment: Beyond FDG PET Score.

BACKGROUND: in recent years, the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) has emerged as a reliable diagnostic tool in a wide variety of pathological conditions. This review aims to collect and review PET criteria developed for interpretation and treatment response assessment in cases of non-[18F]fluorodeoxyglucose ([18F]FDG) imaging in oncology. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus and Google Scholar databases was made to find relevant published articles about non-[18F]FDG PET response criteria. RESULTS: The comprehensive computer literature search revealed 183 articles. On reviewing the titles and abstracts, 149 articles were excluded because the reported data were not within the field of interest. Finally, 34 articles were selected and retrieved in full-text versions. CONCLUSIONS: available criteria are a promising tool for the interpretation of non-FDG PET scans, but also to assess the response to therapy and therefore to predict the prognosis. However, oriented clinical trials are needed to clearly evaluate their impact on patient management.

Radiolabeled Dendrimer Coated Nanoparticles for Radionuclide Imaging and Therapy: A Systematic Review.

BACKGROUND: Dendrimers are nanoscale-size polymers with a globular structure. They are composed of an internal core and branching dendrons with surface active groups which can be functionalized for medical applications. Different complexes have been developed for imaging and therapeutic purposes. This systematic review aims to summarize the development of newer dendrimers for oncological applications in nuclear medicine. METHODS: An online literature search was conducted on Pubmed, Scopus, Medline, Cochrane Library, and Web Of Science databases selecting published studies from January 1999 to December 2022. The accepted studies considered the synthesis of dendrimer complexes for oncological nuclear medicine imaging and therapy. RESULTS: 111 articles were identified; 69 articles were excluded because they did not satisfy the selection criteria. Thus, nine duplicate records were removed. The remaining 33 articles were included and selected for quality assessment. CONCLUSION: Nanomedicine has led researchers to create novel nanocarriers with high affinity for the target. Dendrimers represent feasible imaging probes and therapeutic agents since, through the functionalization of external chemical groups and thanks to the possibility to carry pharmaceuticals, it can be possible to exploit different therapeutic strategies and develop a useful weapon for oncological treatments.

PET Imaging of Neuro-Inflammation with Tracers Targeting the Translocator Protein (TSPO), a Systematic Review: From Bench to Bedside.

Parkinson's disease is the second most common neurodegenerative disorder, affecting 2-3% of the population of patients >65 years. Although the standard diagnosis of PD is clinical, neuroimaging plays a key role in the evaluation of patients who present symptoms related to neurodegenerative disorders. MRI, DAT-SPECT, and PET with [18F]-FDG are routinely used in the diagnosis and focus on the investigation of morphological changes, nigrostriatal degeneration or shifts in glucose metabolism in patients with parkinsonian syndromes. The aim of this study is to review the current PET radiotracers targeting TSPO, a transmembrane protein that is overexpressed by microglia in another pathophysiological process associated with neurodegenerative disorders known as neuroinflammation. To the best of our knowledge, neuroinflammation is present not only in PD but in many other neurodegenerative disorders, including AD, DLB, and MSA, as well as atypical parkinsonian syndromes. Therefore, in this study, specific patterns of microglial activation in PD and the differences in distribution volumes of these radiotracers in patients with PD as compared to other neurodegenerative disorders are reviewed.

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule.

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics-Where We Are at and Where We Are Heading: A Systematic Review.

Cancer is the leading cause of death around the globe, followed by heart disease and stroke, with the highest mortality to this day. We have reached great levels of understanding of how these various types of cancer operate at a cellular level and this has brought us to what we call "precision medicine" where every diagnostic examination and the therapeutic procedure is tailored to the patient. FAPI is among the new tracers that can be used to assess and treat many types of cancer. The aim of this review was to gather all the known literature on FAPI theranostics. A MEDLINE search was conducted on four web libraries, PUBMED, Cochrane, Scopus, and Web of Sciences. All of the available articles that included both diagnoses and therapy with FAPI tracers were collected and put through the CASP (Critical Appraisal Skills Programme) questionnaire for systematic reviewing. A total of 8 records were deemed suitable for CASP review, ranging from 2018 to November 2022. These studies were put through the CASP diagnostic checklist, in order to assess the goal of the study, diagnostic and reference tests, results, descriptions of the patient sample, and future applications. Sample sizes were heterogeneous, both for size as well as for tumor type. Only one author studied a single type of cancer with FAPI tracers. Progression of disease was the most common outcome, and no relevant collateral effects were noted. Although FAPI theranostics is still in its infancy and lacks solid grounds to be brought into clinical practice, it does not show any collateral effects that prohibit administration to patients, thus far, and has good tolerability profiles.