Alice Lorenzoni

Post-Synthesis Incorporation of 64Cu in CuS Nanocrystals to Radiolabel Photothermal Probes: A Feasible Approach for Clinics

We report a simple method for the incorporation of Cu(I) or (64)Cu(I) radionuclides in covellite nanocrystals (CuS NCs). After the in situ reduction of Cu(II) or (64)Cu(II) ions by ascorbic acid, their incorporation in PEG-coated CuS NCs takes place at room temperature. In all the reaction steps, the stability of the NCs under physiological conditions was ensured. The copper incorporation reaction could also take place on CuS NCs bearing biotin molecules at their surface, with no detrimental effects on the specific binding affinity of the NCs toward streptavidin after incorporation. At low loading of Cu ions, the strong near-infrared (NIR) absorption band of the starting CuS NCs was essentially preserved, which allowed for efficient plasmonic photothermal therapy. The combined presence in the NCs of (64)Cu ions, well suitable for positron emission tomography, and of free carriers responsible for the NIR absorption, should enable their theranostic use as radiotracers and as photothermal probes in tumor ablation treatments. Moreover, the simplicity of the preparation scheme, which involves the use of radioactive species only as a last step, makes the protocol easily transferable to the clinical practice.

FDG-PET/CT to predict optimal primary cytoreductive surgery in patients with advanced ovarian cancer: preliminary results.

Aims and background Primary cytoreductive surgery (CRS) has a significant impact on prognosis in epithelial ovarian cancer (EOC). Patient selection is important to recognize factors limiting optimal CRS and to avoid unnecessary aggressive surgical procedures. We evaluated the contribution of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the presurgical identification of disease sites that may preclude EOC cytoreducibility. Methods Patients with suspected EOC underwent 18F-FDG-PET/CT within 20 days before debulking surgery. The PET/CT results were compared with surgical findings and postsurgery histopathology in order to assess the diagnostic value. Results Between August 2013 and January 2014, 29 patients were evaluated. The histopathology showed 23 EOC and 6 benign tumors. The FDG-PET/CT was positive (maximum standardized uptake value [SUVmax] 11.3 ± 5.4) in 21/23 (91%) patients with EOC and provided 2 false-negatives (1 mucinous and 1 clear cell carcinoma; SUVmax ≤2.8). The FDG-PET/CT was true-negative (SUVmax 2.2 ± 1.6) in 4 out of 6 patients (67%). False-positive FDG-PET results were obtained in 2 cellular fibromas (SUVmax 4.8 and 5.6). The sensitivity, specificity, and accuracy of PET/CT to characterize ovarian masses were 91%, 67%, and 86%, respectively. Among the 21 FDG-PET/CT-positive EOC, we detected factors limiting optimal CRS in 6 cases (29%): 4 hepatic hilum infiltration and 2 root mesentery involvement, confirmed at surgical exploration. The FDG-PET did not find limiting factors in the remaining 15 patients (71%) in whom optimal CRS was obtained. Conclusions Fluorodeoxyglucose-PET/CT shows high sensitivity but suboptimal specificity in the characterization of ovarian masses. However, PET/CT may play a role in noninvasively selecting patients with EOC who can benefit from primary CRS.

Single-photon emission computed tomography tracers in the diagnostics of neuroendocrine tumors.

Different imaging strategies have been developed targeting the peculiar features of neuroendocrine tumors (NETs). Metabolic characteristics and receptor expression on the tumor surface have been studied, and expertise and knowledge are increasing as a result of the implementation of fusion imaging and the development of more detailed positron emission tomography tracers. Scintigraphic study of NETs is the most diffused and convenient technique for evaluating patients suspected to have NETs.

Safety and antitumor efficacy of 153Sm-EDTMP and docetaxel administered sequentially to patients with metastatic castration-resistant prostate cancer

BackgroundBone metastases are responsible for most of the morbidity associated with metastatic castration-resistant prostate cancer (mCRPC). Bone-seeking radiopharmaceuticals have been approved for palliation of painful skeletal metastases, but their clinical use is limited by concerns of toxicities both when administered alone and especially when combined with chemotherapy agents. ObjectiveWe investigated whether docetaxel administered to mCRPC patients after treatment with samarium-153-labeled ethylene-diamine-tetra-methylene-phosphonic acid (153Sm-EDTMP) has increased toxicity and/or reduced antitumor efficacy. Materials and methodsThirty mCRPC patients with skeletal metastases were enrolled. Patients received standard therapy with docetaxel (75 mg/m2 intravenously every 21 days for at least six cycles) on average 6 weeks after 153Sm-EDTMP (37 MBq/kg). Patients were monitored for the presence of toxicities, and antitumor efficacy was assessed by changes in serum prostate-specific antigen levels. Besides standard descriptive statistical analysis, progression-free survival and overall survival were defined using the Kaplan–Meier method. ResultsOver 80% of the patients showed favorable biochemical responses. Median time to progression was 9.1 months (mean 9.8, 95% confidence interval 7.8–9.9), and median overall survival was 19.9 months (mean 24.5, 95% confidence interval 16.9–22.8); five patients were still alive over 5 years after enrollment. No additional hematological toxicities were observed when docetaxel was administered after 153Sm-EDTMP other than those expected when administering the agent alone. ConclusionPrior administration of 153Sm-EDTMP does not cause additional toxicities for subsequent treatment with docetaxel and does not reduce the antitumor efficacy of the latter. This work justifies further investigations on the possible synergistic effects of combined strategies with the two agents.

Simultaneous detection of breast tumor resection margins and radioguided sentinel node biopsy using an intraoperative electronically collimated probe with variable energy window: a case report.

Breast-conserving surgery with intraoperative assessment of lesion margins and sentinel lymph node biopsy has become the preferred method of treatment for selected patients with early infiltrating breast cancer. A high-energy gamma probe, designed according to a novel concept of electronic collimation and variable energy window, was used in a patient with nonpalpable infiltrating breast cancer to perform simultaneous intraoperative identification of lesion margins (based on the detection of the high-energy gamma rays originated from annihilation following preoperative administration of F-18 FDG) and radioguided sentinel node biopsy (based on the single-photon agent Tc-99m-nanocolloid used for lymphoscintigraphy).

Evolution in the treatment of gastroenteropancreatic-neuroendocrine neoplasms, focus on systemic therapeutic options: a systematic review.

Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors. The present review discusses current therapeutic strategies for the treatment of gastro-entero-pancreatic NEN. Several systemic options are currently available, including medical systemic chemotherapy, biological drugs, somatostatin analogs and peptide receptor radionuclide therapy. The carcinoid syndrome can be adequately controlled with somatostatin analogs; chemotherapy has shown positive outcomes in poor prognosis patients, and peptide receptor radionuclide therapy is a promising treatment based on the use of radioisotopes for advanced disease expressing somatostatin receptors. Targeted therapies, such as multikinase inhibitors and monoclonal antibodies are also recommended or under evaluation for the treatment of advanced NENs, but some critical issues in clinical practice remain unresolved. Depending upon the development of the disease, a multimodal approach is recommended. The treatment strategy for metastatic patients should be planned by a multidisciplinary team in order to define the optimal sequence of treatments.

Intrahepatic Flow Redistribution in Patients Treated with Radioembolization

IntroductionIn planning Yttrium-90 (90Y)-radioembolizations, strategy problems arise in tumours with multiple arterial supplies. We aim to demonstrate that tumours can be treated via one main feeding artery achieving flow redistribution by embolizing accessory vessels.MethodsOne hundred 90Y-radioembolizations were performed on 90 patients using glass microspheres. In 19 lesions/17 patients, accessory branches were found feeding a minor tumour portion and embolized. In all 17 patients, the assessment of the complete perfusion was obtained by angiography and single photon emission computerized tomography–computerized tomography (SPECT–CT). Dosimetry, toxicity, and tumor response rate of the patients treated after flow redistribution were compared with the 83 standard-treated patients. Seventeen lesions in 15 patients with flow redistribution were chosen as target lesions and evaluated according to mRECIST criteria.ResultsIn all patients, the complete tumor perfusion was assessed immediately before radioembolization by angiography in all patients and after the 90Y-infusion by SPECT–CT in 15 of 17 patients. In the 15 assessable patients, the response rate in their 17 lesions was 3 CR, 8 PR, and 6 SD. Dosimetric and toxicity data, as well tumour response rate, were comparable with the 83 patients with regular vasculature.ConclusionsAll embolization procedures were performed successfully with no complications, and the flow redistribution was obtained in all cases. Results in term of toxicity, median dose administered, and radiological response were comparable with standard radioembolizations. Our findings confirmed the intratumoral flow redistribution after embolizing the accessory arteries, which makes it possible to treat the tumour through its single main feeding artery.

Multiagent imaging of liver tumors with reference to intra-arterial radioembolization

Intra-arterial radioembolization using microspheres labeled with the high-energy beta-emitter yttrium-90 (90Y) is an innovative therapeutic strategy for primary and secondary hepatic malignancies. An accurate imaging workup plays a pivotal role in correctly selecting patients for treatment, to avoid severe complications and in assessment of the post-administration microsphere distribution. Nuclear medicine imaging modalities are an integral part of a complex multidisciplinary approach. In particular, hepatic perfusion imaging with 99mTc-macroaggregated albumin particles (99mTc-MAA), which identifies extrahepatic accumulation of radiopharmaceutical and lung shunt, is necessary to correctly select patients who may benefit from the treatment. Furthermore, 99mTc MAA SPECT-based dose planning may optimize RE efficacy, overcoming the limitations of empirical methods to determine the activity to be administered. Quantitative assessment of the post-administration intrahepatic microsphere distribution with SPECT or PET is important for evaluation of toxicity and efficacy and can be used for the prediction of patient response and for patient-specific therapeutic dose optimization. Finally, [18F]FDG PET/CT imaging is important in the assessment of early response after RE and in predicting patient outcome. This review provides a comprehensive overview of multimodality imaging in the complex management of patients undergoing RE for liver tumors.

Sentinel Lymph Node Biopsy in Pelvic Tumors: Clinical Indications and Protocols Under Investigation.

Abstract Sentinel lymph node (SLN) sampling is an attractive alternative to complete lymphadenectomy. Based on the identification and sampling of the first LN draining a primary tumor, SLN biopsy is the most accurate and the only reliable method for microscopic nodal staging for solid tumors including breast cancer and melanoma. Lymph node status in pelvic tumors remains the most important prognostic factor for recurrence and survival and a major decision criterion for adjuvant therapy. We review the clinical indications, controversies, and perspective of SLN biopsy in male and female pelvic cancers.

Treatment with 131 I-mIBG (Metaiodobenzylguanidine): Indications, Procedures, and Results

Since the 80s, treatment with 131I-metaiodobenzylguanidine (mIBG) has been introduced in the management of neuroendocrine tumors (NET). In several chromaffin tumors (neuroblastoma, pheochromocytoma, paraganglioma), but also medullary thyroid carcinoma and carcinoids, the efficacy and the possible role of 131I-mIBG treatment along disease course have been extensively investigated.