Artor Niccoli Asabella

The Copper Radioisotopes: A Systematic Review with Special Interest to 64Cu

Copper (Cu) is an important trace element in humans; it plays a role as a cofactor for numerous enzymes and other proteins crucial for respiration, iron transport, metabolism, cell growth, and hemostasis. Natural copper comprises two stable isotopes, 63Cu and 65Cu, and 5 principal radioisotopes for molecular imaging applications (60Cu, 61Cu, 62Cu, and 64Cu) and in vivo targeted radiation therapy (64Cu and 67Cu). The two potential ways to produce Cu radioisotopes concern the use of the cyclotron or the reactor. A noncopper target is used to produce noncarrier-added Cu thanks to a chemical separation from the target material using ion exchange chromatography achieving a high amount of radioactivity with the lowest possible amount of nonradioactive isotopes. In recent years, Cu isotopes have been linked to antibodies, proteins, peptides, and nanoparticles for preclinical and clinical research; pathological conditions that influence Cu metabolism such as Menkes syndrome, Wilson disease, inflammation, tumor growth, metastasis, angiogenesis, and drug resistance have been studied. We aim to discuss all Cu radioisotopes application focusing on 64Cu and in particular its form 64CuCl2 that seems to be the most promising for its half-life, radiation emissions, and stability with chelators, allowing several applications in oncological and nononcological fields.

Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl2. To evaluate the potential theranostic role of [64Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

18F-FDG PET/CT role in staging of gastric carcinomas: comparison with conventional contrast enhancement computed tomography.

AbstractThe purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT).This retrospective study included 45 patients who underwent performed whole body CECT and 18F-FDG PET/CT before any treatment. We calculated CECT and 18F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of 18F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy, PPV and NPV of CECT, and 18F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and 18F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and 18F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. 18FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases.The 18F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with 18F-FDG PET/CT permits a more valid staging in these patients.

124Iodine: A Longer-Life Positron Emitter Isotope—New Opportunities in Molecular Imaging

124Iodine (124I) with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of 124I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with 124I. Advances in radionuclide production allow the effective availability of sufficient quantities of 124I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with 124I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of 124I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with 124I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on 124I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields.

F-18 FDG PET/CT in the diagnosis of a rare case of neurosarcoidosis in a patient with diabetes insipidus.

We report a case of a 26-year-old man who had sarcoidosis with involvement of central nervous system, manifested by symptoms attributable to diabetes insipidus. Laboratory tests, magnetic resonance and computed tomography images, were all partially useful and inconclusive. These investigations have been integrated with 18-Fluorine-labeled-2-deoxy-2-fluoro-Dglucose positron-emission-tomography/computed tomography (F-18 FDG PET/CT), which showed F-18 FDG uptake in the midbrain area and pituitary gland, corresponding to magnetic resonance findings, and in many bone sites, in particular iliac wings. This finding has been useful for biopsy. F-18 FDG PET/CT can demonstrate active skull-base sarcoidosis.

Multimodality Imaging in Tumor Angiogenesis: Present Status and Perspectives

Angiogenesis is a complex biological process that plays a central role in progression of tumor growth and metastasis. It led to a search for antiangiogenic molecules, and to design antiangiogenic strategies for cancer treatment. Noninvasive molecular imaging, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), could be useful for lesion detection, to select patients likely to respond to antiangiogenic therapies, to confirm successful targeting, and dose optimization. Additionally, nuclear imaging techniques could also aid in the development of new angiogenesis-targeted drugs and their validation. Angiogenesis imaging can be categorized as targeted at three major cell types: (I) non-endothelial cell targets, (II) endothelial cell targets, and (III) extracellular matrix proteins and matrix proteases. Even if radiopharmaceuticals studying the metabolism and hypoxia can be also used for the study of angiogenesis, many of the agents used in nuclear imaging for this purpose are yet to be investigated. The purpose of this review is to describe the role of molecular imaging in tumor angiogenesis, highlighting the advances in this field.

Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment

Abstract We investigated the prognostic value of interim 18F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis. Thirty pHL patients (age ⩽16) underwent serial 18F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (&Dgr;&Sgr;SUVmax0–2, &Dgr;&Sgr;SUVmean0–2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3–78). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan–Meier method. Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for &Dgr;&Sgr;SUVmax0–2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between &Dgr;&Sgr;SUVmax0–2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P = 0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P = 0.005). Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (&Dgr;&Sgr;SUVmax0–2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies.

Comparison between CT Net enhancement and PET/CT SUV for N staging of gastric cancer: A case series

Background The therapeutic approach of gastric cancer strictly depends on TNM staging mainly provided by CT and PET/CT. However, the lymph node size criterion as detected by MDCT causes a poor differential diagnosis between reactive and metastatic enlarged lymph nodes with low specificity values. Our study aims to compare 320-row CT Net enhancement and fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (F-FDG PET/CT) SUV for N staging of gastric cancer. Materials and methods 45 patients with histologically proven gastric cancer underwent CT and F-FDG PET/CT. Two radiologists in consensus evaluated all images and calculated the CT Net enhancement and F-FDG PET/CT SUV for N staging, having the histological findings as the reference standard. CT and F-FDG PET/CT sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (PPV and NPV) were evaluated and compared by using the Mc Nemar test. Results The histological examination revealed nodal metastases in 29/45 cases (64%). CT Net enhancement obtained sensitivity, specificity, accuracy, PPV and NPV of 90%, 81%, 87%, 90% and 81%, respectively. F-FDG PET/CT SUV obtained sensitivity, specificity, accuracy, PPV and NPV of 66%, 88%, 73%, 90% and 58%, respectively. No statistically significant difference between the two imaging modalities was found (p = 0.1). Conclusion CT Net enhancement represents an accurate tool for N staging of gastric cancer and could be considered as the CT corresponding quantitative parameter of F-FDG PET/CT SUV. It could be applied in the clinical practice for differentiating reactive lymph nodes from metastatic ones improving accuracy and specificity of CT.

A pilot study employing hepatic intra-arterial irinotecan injection of drug-eluting beads as salvage therapy in liver metastatic colorectal cancer patients without extrahepatic involvement: the first southern Italy experience

Background The main aim of this prospective study was to evaluate the efficacy of drug-eluting beads with irinotecan (DEBIRI) for liver metastases from colorectal cancer. Secondary aims were to evaluate survival and toxicity. Methods Twenty-five patients with metastases in <50% of the liver and without extrahepatic involvement were enrolled. Treatment response assessment was performed by multidetector contrast enhancement computed tomography (MDCT) with evaluation of the enhancement pattern of the target lesion and tumor response rates according to modified Response Evaluation Criteria in Solid Tumors (mRECIST, Version 1.1). All adverse events were recorded by the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 3.0. Associations of tumor response and variables were calculated using the chi-squared test. Overall survival (OS) was calculated using the Kaplan–Meier method. Comparisons were made using the log-rank test. Results According to mRECIST, complete response (CR) was observed in 21.8% of patients, partial response (PR) in 13%, stable disease (SD) in 52.2% and progressive disease (PD) in 13% of patients. Response rate (RR = CR + PR) was 34.8%. No associations between treatment response and variables such as Dukes’ classification, grading and Kras status were found (P>0.05). The median OS was 37 months (95% CI: 13.881 to 60.119). Cox regression model showed that neither site, Dukes’ classification, grading, Kras status nor number of chemotherapy treatments pre-DEBIRI influenced the OS. The log-rank test showed no statistically significant difference in OS among patients who underwent 1, 2 or 3 DEBIRI treatments (χ2=2.831, P=0.09). In our study, the main toxicities included postembolization syndrome (PES), hypertransaminasemia and fever. Conclusion The favorable tumor response and the favorable toxicity profile make DEBIRI treatment a potential third-line therapy. Although further larger studies are needed to confirm these data, we can state that DEBIRI is an attractive emerging treatment in these patients.

18F-FDG Positron Emission Tomography/Computed Tomography in the Diagnosis and Post-Therapeutic Treatment in a Patient with an Early Stage of Retroperitoneal Fibrosis

Here, we report an experience about 18F-FDG-PET/CT in a patient with an early stage of Idiopathic Retroperitoneal Fibrosis (IRF). At the diagnosis Contrast Enhanced Computed Tomography (CE-CT) revealed periaortic solid tissue in the infrarenal section and locoregional lymph nodes; findings were interpreted as lymphomatous tissue. 18F-FDG-PET/CT showed elevated 18F-FDG uptake in the periaortic tissue but no uptake was detected in lymph nodes. The histologic examination showed recent-onset IRF. The patient began corticosteroid therapy. Nearly at the end of the therapy, CE-CT showed the enlargement of the fibrous tissue and 18F-FDG-PET/CT showed an increased 18F-FDG uptake in the aforesaid lesion and another area of uptake in the aortic wall. 18F-FDG-PET/CT can play an important role in the diagnosis of patients with an initial clinical suspicion of retroperitoneal fibrosis and in their management. Then the patient began a therapy with methotrexate and after six months we performed an 18F-FDG-PET/CT which didn’t show 18F-FDG uptake. Conflict of interest:None declared.