18F-fluorodeoxyglucose (18F-FDG) Functionalized Gold Nanoparticles (GNPs) for Plasmonic Photothermal Ablation of Cancer: A Review.

The meeting and merging between innovative nanotechnological systems, such as nanoparticles, and the persistent need to outperform diagnostic-therapeutic approaches to fighting cancer are revolutionizing the medical research scenario, leading us into the world of nanomedicine. Photothermal therapy (PTT) is a non-invasive thermo-ablative treatment in which cellular hyperthermia is generated through the interaction of near-infrared light with light-to-heat converter entities, such as gold nanoparticles (GNPs). GNPs have great potential to improve recovery time, cure complexity, and time spent on the treatment of specific types of cancer. The development of gold nanostructures for photothermal efficacy and target selectivity ensures effective and deep tissue-penetrating PTT with fewer worries about adverse effects from nonspecific distributions. Regardless of the thriving research recorded in the last decade regarding the multiple biomedical applications of nanoparticles and, in particular, their conjugation with drugs, few works have been completed regarding the possibility of combining GNPs with the cancer-targeted pharmaceutical fluorodeoxyglucose (FDG). This review aims to provide an actual scenario on the application of functionalized GNP-mediated PTT for cancer ablation purposes, regarding the opportunity given by the 18F-fluorodeoxyglucose (18F-FDG) functionalization.

The prognostic value of 123I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review.

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine (123I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of 123I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words "MIBG", "metaiodobenzylguanidine", "heart", "spect", and "tomographic". The included studies had to correlate 123I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced 123I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for 123I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional 123I-mIBG planar myocardial imaging.

Radium-223 in mCPRC patients: a large real-life Italian multicenter study.

BACKGROUND: Radium-223 is a targeted alpha-particles therapy approved for the treatment of mCRPC patients with symptomatic bone metastases. To our knowledge we account for the largest cohort of mCRPC patients subjected to Radium-223 treatment in our country. We aim to describe in a real-life setting the largest cohort of mCRPC patients treated with Radium-223 ever taken into consideration. METHODS: Four hundred and thirty consecutive mCRPC patients were enrolled. Clinical data have been collected at baseline and at the end of the Radium-223 treatment. Furthermore, the overall survival(OS) of our population has been provided. RESULTS: One hundred fifty-seven patients (36.5%) were still alive at the time of data analysis. A mean number of 4.95±1.6 cycles of Radium-223 was reached by our cohort. 265 patients (61.6%) completed the whole six cycles regimen. The mean follow-up period from the first cycle of Radium-223 to the date of the analysis was 12.7 months. The analysis of patients Annual Incidence Rate (AIR) in relation to the number of Radium-223 cycles received depicting a clear advantage for those patients who completed the whole six administrations planned, with an AIR (AIR=0.32) of much lesser value compared to those that have performed five cycles (AIR =0.98). 165 patients (38.4%) dropped out of treatment for death or disease progression. CONCLUSIONS: This study offers a cross-section of the clinical performance of Radium-223 treatment in a real-world context, confirming on a large scale the effectiveness of Radium-223 in improving the OS and quality of life, along with the preservation of an excellent safety profile.

Potential prognostic value of miR-132 and miR-212 expression in mCRPC patients.

To the Editor, we have been very pleased to read the interesting work proposed by Salemi et al. regarding the expression of specific fragments of microRNA (miRNA), particularly miR-132 and miR-212, as potential key regulators in prostate cancer (PCa). As outlined by the Authors, the altered expression of miRNAs in cancer pathogenesis represents a well-consolidated knowledge in the current literature. More specifically, both miR-212 and miR-132 regulate subsets of genes involved in tumor progression in several tumor cell types as PCa, proving a central role in tumorigenesis, cell adhesion, and angiogenesis. In addition, a strong association between miR-132 expression and high Gleason score PCa has been lately depicted [...].

Radium-223 Treatment in mCRPC Patient with Polycythemia Vera

There have been several studies on the clinical outcomes of Radium-223 treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) who may have an increased risk of hematologic comorbidities. To the best of our knowledge, this is the first study to explore the potential bone marrow adverse effects (AEs) of Radium-223 administered with specific drugs used for hematologic conditions, such as polycythemia vera (PV). We report the case of a patient with mCRPC who was administered a combined treatment of Radium-223 and hydroxyurea for PV, aiming to support clinicians in predicting eventual AEs.

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients' pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called "theranostic" approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors' analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC.

Unexpected Detection of Abscessualized Lung Carcinoma on Tc-99m-HMPAO-labeled Leukocytes Scintigraphy Misdiagnosed on Chest Computed Tomography.

Technetium-99m (Tc-99m)-hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes scintigraphy is well established for investigating and diagnosing infections in bone and soft tissue, as well as for the detection of occult infection. A 71-year-old female who was recently diagnosed with bronchopulmonary neuroendocrine tumor of the right lung was referred for an intermittent fever of unknown origin associated with chill at night for the last month. Chest computed tomography (CT) scan showed a thrombotic widespread of the superior vena cava and a solid pathological tissue in the superior segment of the inferior lobe of the right lung with consensual atelectasis. Being a carrier of port-a-cath, an infection of this device was suspected. Therefore, Tc-99m-HMPAO-labeled leukocytes single-photon emission computed tomography (SPECT) was performed, and matching pairs of CT scan and Tc-99m-HMPAO-labeled white blood cell SPECT images were fused. Through this means, it was found that the area of the radiotracer increased uptake corresponded with the soft tissue density mass detected by CT scan localized at the inferior lobe of the right lung. The hybrid SPECT/CT fused imaging was crucial for diagnosis of the presence of a lung abscess localized in correspondence with the known lung cancer region.

123I-FP-CIT Brain SPECT Findings in Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency.

BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. Neuroimaging findings are commonly considered rather non-specific. To date, no neuroreceptorial brain imaging with 123I-FP-CIT(DaTScan) is known in subjects with SSADH deficiency. METHODS: A 30-year-old man gained our attention to rule out any potential nigrostriatal dopaminergic presynaptic pathway alterations in a clinical context of a γ-hydroxybutyric aciduria. He showed impossibility to the autonomous gait, head and trunk retropulsion, lower limbs strength deficit, verbal and upper limbs motor stereotypies and irregular eye tracking. RESULTS: His brain MRI depicted basal ganglia signal abnormalities. Brain SPECT with DaTSCan images showed a global significant reduction of radiotracer uptake. CONCLUSIONS: The findings obtained by means of the 123I-DaTScan brain SPECT may give rise to new concerns on pathophysiological aspects of the SSADH deficiency disorder that has never been investigated before, such as the nigrostriatal dopaminergic system's functionality, encouraging further investigation.

111In-Octreoscan SPECT/CT hybrid imaging and 68Ga-DOTANOC PET/CT in neuroendocrine adenoma of the middle ear (NAME).

Neuroendocrine adenoma of the middle ear (NAME) represents a rare tumour consisting of an adenoma with mixed neuroendocrine differentiation. A 40-year-old woman was referred to our attention to further investigate the occurrence of a pathological tissue located in the mastoid process of the left temporal bone depicted by head CT and MRI scans. Histopathological examination revealed an epithelial neoplasm with neuroendocrine differentiation features, consistent with the diagnosis of NAME. In order to obtain an accurate differential diagnosis and confirmation of this rare disease, 111In-Octreoscan single photon emission computed tomography (SPECT)/CT and 68Ga-DOTANOC positron emission tomography (PET)/CT were performed, both showing overexpression of somatostatin receptors and thus corroborating the histopathological findings.

Bone pain palliation outcomes and possibility of Radium-223 re-treatment in mCRPC.

OBJECTIVE: Bone secondary localizations from metastatic castration-resistant prostate cancer are associated with an increase in mortality and a reduction in the patient's quality of life. Radium-223 is a targeted alpha-therapy approved for the treatment of mCRPC (metastatic castration resistant prostate cancer) patients with symptomatic bone metastases. To our knowledge, no previous study has been performed assessing the bone pain palliation outcomes following Radium-223 therapy. MATERIALS AND METHODS: A mCRPC patient with symptomatic bone localizations and relevant bone pain symptoms has been subjected to Radium-223 treatment. Pain was assessed over time from the first administration of Radium-223 to follow-up. RESULTS: After Radium-223 treatment, patient showed a significant BPI (Brief Pain Inventory) decline from 7 to 4 and a concomitant partial regression of multiple bone hot spots in the bone scan exam. Three months after the last infusion of Radium-223, further BPI decline (from 4 to 2) with bone scan depicting stable disease was observed. However, after 6 months from Radium-223 treatment end, BPI increased from 2 to 10. CONCLUSIONS: Taking into account the effectiveness on bone pain relief and the low toxicity profile showed by Radium-223 treatment, we encourage further analysis on large cohort to investigate the clinical outcome after Radium-223 treatment, in terms of bone pain palliation, together with the possibility of Radium-223 re-treatment in selected patients..

Role of Nuclear Imaging in Cardiac Amyloidosis Management: Clinical Evidence and Review of Literature.

Cardiac amyloidosis (CA) is an infiltrative disease characterized by the extracellular deposition of fibrils, amyloid, in the heart. The vast majority of patients with CA has one of two types between transthyretin amyloid (ATTR) and immunoglobulin light chain associated amyloid (AL), that have different prognosis and therapeutic options. CA is often underdiagnosed. The histological analysis of endomyocardial tissue is the gold standard for the diagnosis, although it has its limitations due to its invasive nature. Nuclear medicine now plays a key role in the early and accurate diagnosis of this disease, and in the ability to distinguish between the two forms. Recent several studies support the potential advantage of bone-seeking radionuclides as a screening technique for the most common types of amyloidosis, in particular ATTR form. This review presents noninvasive modalities to diagnose CA and focuses on the radionuclide imaging techniques (bone-seeking agents scintigraphy, cardiac sympathetic innervation and positron emission tomography studies) available to visualize myocardial amyloid involvement. Furthermore, we report the case of an 83-year old male with a history of prostate cancer, carcinoma of the cecum and kidney cancer, submitted to bone scan to detect bone metastasis, that revealed a myocardial uptake of 99mTC-HMPD suggestive of ATTR CA. An accurate and early diagnosis of CA able to distinguish beyween AL and ATTR CA combined to the improving therapies could improve the survival of patients with this disease.

New Frontiers in Molecular Imaging with Superparamagnetic Iron Oxide Nanoparticles (SPIONs): Efficacy, Toxicity, and Future Applications.

Supermagnetic Iron Oxide Nanoparticles (SPIONs) are nanoparticles that have an iron oxide core and a functionalized shell. SPIONs have recently raised much interest in the scientific community, given their exciting potential diagnostic and theragnostic applications. The possibility to modify their surface and the characteristics of their core make SPIONs a specific contrast agent for magnetic resonance imaging but also an intriguing family of tracer for nuclear medicine. An example is 68Ga-radiolabeled bombesin-conjugated to superparamagnetic nanoparticles coated with trimethyl chitosan that is selective for the gastrin-releasing peptide receptors. These receptors are expressed by several human cancer cells such as breast and prostate neoplasia. Since the coating does not interfere with the properties of the molecules bounded to the shell, it has been proposed to link SPIONs with antibodies. SPIONs can be used also to monitor the biodistribution of mesenchymal stromal cells and take place in various applications. The aim of this review of literature is to analyze the diagnostic aspect of SPIONs in magnetic resonance imaging and in nuclear medicine, with a particular focus on sentinel lymph node applications. Moreover, it is taken into account the possible toxicity and the effects on human physiology to determine the SPIONs' safety.

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study.

BACKGROUND: We investigated, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy [RP] or external beam radiotherapy [EBRT]) on overall survival for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (223Ra). MATERIALS AND METHODS: In the present multicenter retrospective study, we enrolled 275 consecutive patients. The demographic and clinical data and mCRPC characteristics were recorded and evaluated at baseline and at the end of treatment or progression. 223Ra was administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: those who had undergone primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and those who had not received previous primary treatment (NO). RESULTS: Of the 275 patients, 128 (46.5%) were alive and undergoing monitoring at the last follow-up examination, 103 (37.4%) had stopped treatment because of disease progression or the onset of comorbidities, and 147 (53.5%) had died during the study period. Of the 275 patients, 132 were in the RP/EBRT group (48%), of whom 93 had undergone RP and 76 had undergone ablative EBRT, and 143 patients were in the NO group (52%). The data showed a clear advantage for the patients in the RP/EBRT group compared with those in the NO group, with an estimated median survival of 18 versus 11 months, respectively (P < .001). The results from the multivariate analysis corroborated this trend, with a hazard ratio of 0.7 (P = .0443), confirming the better outcome for the RP/EBRT group. CONCLUSIONS: Previous radical treatment provides a protective role for patients with mCRPC undergoing 223Ra treatment.

Baseline quality of life predicts overall survival in patients with mCRPC treated with 223Ra-dichloride.

OBJECTIVE: The prognostic value of baseline clinical parameters in predicting the survival prolonging effect of radium-223-dichloride (223Ra)-therapy in metastatic castration resistant prostate cancer (mCRPC) patients is still an open issue. The aim of this study was investigating the impact of baseline quality of life (QoL) on overall survival (OS) in mCRPC patients treated with 223Ra. The present study also evaluated the trend of patient-reported QoL during both 223Ra-treatment and post-therapy follow-up period. MATERIALS AND METHODS: One hundred and seventy-three consecutive mCRPC patients treated with 223Ra were included in this prospective study. Quality of life was assessed through EORTC QLQ-C30 and QLQ-BM22 questionnaires and 2264 questionnaires were evaluated. Other baseline variables relevant to the OS analysis have been considered. Data were summarized using descriptive statistics, univariate and multivariate analysis with Cox model. A principal component analysis (PCA) on the questionnaires' results compiled at baseline was performed to reduce the data to a one-dimensional score. Joint models for survival and longitudinal data were finally used in order to evaluate the relationship between the time-depended QoL scores and OS. RESULTS: On multivariate analysis, baseline patients' hemoglobin (Hb), total alkaline phosphatase (tALP), and two EORTC QLQ-C30 items, physical functioning (HR=0.970,CI=0.960-0.980, P<0.001) and dyspnea (HR=0.992,CI=0.986-0.999, P=0.023), were significantly associated with OS. In the resulting model of the multivariate analysis performed after PCA, baseline patients' Hb, tALP and QoL-score were independent significant predictors of OS (QoL-score: HR=0.995-95%CI=0.992 - 0.998, P=0.001). The OS analysis stratified by score of baseline QoL, showed a median OS of 8 (95%CI=6-11) and 16 (95%CI=12-24) months for scores respectively below and above the cut-off value (log-rank-P<0.001). The joint model showed a significant deterioration of QoL-score during both 223Ra-therapy and follow-up period (P<0.001). CONCLUSION: Baseline QoL is a significant predictor of OS, meaning that patients with better pretreatment QoL are more likely to obtain a marked survival prolonging effect from 223Ra.

Usefulness of 5 Minutes 123I-mIBG Scan in Parkinson's Disease and Heart Failure.

BACKGROUND: The use of 123I-mIBG has been approved for decades for Parkinson's disease (PD) diagnosis and as a predictor of mortality and potentially fatal events in patients with Heart Failure (HF). The standardized technique includes an early acquisition (15 minutes from injection), and a late acquisition (240 minutes). Early images mainly represent interstitial uptake, whereas delayed images represent actual neuronal uptake, however, it is reasonable to affirm that different pathological situations, such as PD and HF, imply a different meaning for early and late imaging. OBJECTIVE: This prospective study aims to investigate the clinical usefulness of an immediate planar 123I-mIBG image acquisition (5 minutes) both in patients with PD and in patients with HF. METHODS: 115 patients referred to 123I-mIBG cardiac imaging in Nuclear Medicine Center have been enrolled (60 patients with PD, absence of diabetes and/or cardiologic pathology, Hoehn e Yahr classification ≤ 1.5; 55 patients with cardiomyopathy, diagnosis of HF, NYHA class I-III). 123I-mIBG planar anterior thoracic acquisitions were performed after 5 (immediate), 15 (early) and 240 (late) minutes from injection and H/M ratios were calculated. RESULTS: In PD group H/M mean values resulted in 1.58±0.22 for immediate (5 min), 1.61±0.26 for early (15 min) and 1.59±0.37 for late (240 min) acquisitions. In the HF group, H/M mean values resulted in 1.63±0.24 for immediate (5 min), 1.65±0.22 for early (15 min) and 1.57±0.17 for late (240 min) acquisitions, respectively. H/M values obtained at 5 min and 15 min are provided similar results, with no statistical difference (p = ns) regardless of the pathology examined (PD or HF groups). The statistical analyses validated the diagnostic role of immediate acquisition (5 min) and early acquisition (15 min) in PD group as compared to the standardized late acquisition (240 min). On the contrary, in HF group, immediate and early acquisition, as compared to late acquisition (240 min), is not validated as a major cardiac events predictor. CONCLUSION: Our results indicate the potential role of immediate (5 min) or early (15 min) acquisition in replacement of standardized 240 minutes acquisition in PD patients, but this result is not confirmed in HF patients, in which the acquisition at 240 min is confirmed as the most affordable timing for image interpretation, emphasizing the different pathophysiology that underlies these two pathologies.

Analysis of Unusual Adverse Effects After Radium-223 Dichloride Administration.

BACKGROUND: To our knowledge, no previous study or literature review has been performed about the effects of the extravasation of therapeutic radiopharmaceutical agents and its potential consequences, especially regarding alpha-particle emitting radiopharmaceuticals. METHODS: Even if Radium-223 dichloride is known to be a relatively safe drug to manage, despite the correctness of the procedures applied , unexpected delayed adverse effects can occur. In our vast experience, we rarely observed lymphedema, even after some time, at the site of administration. RESULTS: Management of lymphedema caused by radiopharmaceuticals administration has been addressed through clinical examples. The sudden intervention allowed a fast remission of the signs and symptoms complained by patients treated with Radium-223 dichloride. CONCLUSION: The management of adverse effects after radiopharmaceuticals administration as in case of lymphedema onset, is extremely simple. These data confirm the safety of Radium-223 treatment.

Paraganglioma de la pared de la vejiga localizado con 123I-mIBG SPECT y TC / Bladder wall paraganglioma located using 123I-mIBG SPECT and CT imaging

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