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1.
The emerging value of 64Cu for molecular imaging and therapy.
Bolzati, C, Duatti, A
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2020;(4):329-337
Abstract
Along with other novel metallic radionuclides, copper-64 (64Cu) is currently being investigated as an alternative option to the gallium-68 (68Ga) and lutetium-177 (177Lu) radiopharmaceuticals widely used for targeting somatostatin receptors, expressed by neuroendocrine tumors (NETs), and recently prostate specific membrane antigen (PSMA), expressed by prostate cancer cells. This interest is mostly driven by the peculiar nuclear properties of 64Cu that make it an almost ideal example of theranostic radionuclide. In fact, 64Cu emits both low-energy positrons, β- particles and a swarm of Auger electrons. This combination of different emissions may allow to collect high-resolution PET images, but also to use the same radiopharmaceutical for eliciting a therapeutic effect. Another unique behavior of 64Cu originates from the fundamental biological role played in organisms by the ionic forms of the copper element, which is naturally involved in a multitude of cellular processes including cell replication. These intrinsic biological characteristics has led to the discovery that 64Cu, under its simplest dicationic form Cu2+, is able to specifically target a variety of cancerous cells and to detect the onset of a metastatic process in its initial stage. This short review reports an outline of the status of 64Cu radiopharmaceuticals and of the most relevant results that are constantly disclosed by preclinical and investigational clinical studies.
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2.
Diagnostic Performance of PET or PET/CT with Different Radiotracers in Patients with Suspicious Lung Cancer or Pleural Tumours according to Published Meta-Analyses.
Lococo, F, Muoio, B, Chiappetta, M, Nachira, D, Petracca Ciavarella, L, Margaritora, S, Treglia, G
Contrast media & molecular imaging. 2020;:5282698
Abstract
PURPOSE Several meta-analyses have reported data about the diagnostic performance of positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) with different radiotracers in patients with suspicious lung cancer (LC) or pleural tumours (PT). This review article aims at providing an overview on the recent evidence-based data in this setting. METHODS A comprehensive literature search of meta-analyses published in PubMed/MEDLINE and Cochrane Library database from January 2010 through March 2020 about the diagnostic performance of PET or PET/CT with different radiotracers in patients with suspicious LC or PT was performed. This combination of keywords was used: (A) "PET" OR "positron emission tomography" AND (B) "lung" OR "pulmonary" OR "pleur∗" AND (C) meta-analysis. Only meta-analyses on PET or PET/CT in patients with suspicious LC or PT were selected. RESULTS We have summarized the diagnostic performance of PET or PET/CT with fluorine-18 fluorodeoxyglucose (18F-FDG) and other radiotracers taking into account 17 meta-analyses. Evidence-based data demonstrated a good diagnostic performance of 18F-FDG PET or PET/CT for the characterization of solitary pulmonary nodules (SPNs) or pleural lesions with overall higher sensitivity than specificity. Evidence-based data do not support the routine use of dual time point (DTP) 18F-FDG PET/CT or fluorine-18 fluorothymidine (18F-FLT) PET/CT in the differential diagnosis of SPNs. Even if 18F-FDG PET/CT has high sensitivity and specificity as a selective screening modality for LC, its role in this setting remains unknown. CONCLUSIONS Evidence-based data about the diagnostic performance of PET/CT with different radiotracers for suspicious LC or PT are increasing, with good diagnostic performance of 18F-FDG PET/CT. More prospective multicenter studies and cost-effectiveness analyses are warranted.
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3.
Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis.
Vardarli, I, Weidemann, F, Aboukoura, M, Herrmann, K, Binse, I, Görges, R
BMC cancer. 2020;(1):550
Abstract
BACKGROUND Regarding the longer-term recurrence rate the optimal activity for the remnant thyroid ablation in patients with differentiated thyroid cancer (DTC) is discussed controversially. For the short-term ablation success rate up to 12 months there are already several meta-analyses. In this study we performed the first meta-analysis regarding the longer-term recurrence rate after radioactive 131-I administration. METHODS We conducted an electronic search using PubMed/MEDLINE, EMBASE and the Cochrane Library. All randomized controlled trials (RCTs) assessed the recurrence rate after radioactive iodine ablation in patients with DTC, with a follow-up of at least two years were selected. Statistics were performed by using Review Manager version 5.3 and Stata software. RESULTS Four RCTs were included in the study, involving 1501 patients. There was no indication for heterogeneity (I2 = 0%) and publication bias. The recurrence rate among patients who had a low dose 131-iodine ablation was not higher than for a high dose activity (odds ratio (OR) 0.93 [95% confidence interval (CI) 0.53-1.63]; P = 0.79). The mean follow-up time was between 4.25 and 10 years. The subgroup analysis regarding the TSH stimulated thyroglobulin values (< 10 ng/mL versus < 2 ng/mL versus ≤1 ng/mL) showed no influence on recurrence rate. CONCLUSIONS For the first time we showed that the longer-term, at least 2-year follow-up, recurrence rate among patients who had 131-iodine ablation with 1.1 GBq was not higher than with 3.7 GBq.
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4.
18F-Sodium Fluoride PET: History, Technical Feasibility, Mechanism of Action, Normal Biodistribution, and Diagnostic Performance in Bone Metastasis Detection Compared with Other Imaging Modalities.
Ahuja, K, Sotoudeh, H, Galgano, SJ, Singh, R, Gupta, N, Gaddamanugu, S, Choudhary, G
Journal of nuclear medicine technology. 2020;(1):9-16
Abstract
The skeleton is the third most common site for metastasis overall, after the lungs and liver. Accurate diagnosis of osseous metastasis is critical for initial staging, treatment planning, restaging, treatment monitoring, and survival prediction. Currently, 99mTc-methylene diphosphonate whole-body scanning is the cornerstone of imaging to detect osseous metastasis. Although 18F-sodium fluoride (18F-NaF) was one of the oldest medical tracers for this purpose, it was replaced by other tracers because of their better physical properties, until recently. Continued development of PET scanners has opened a new era for 18F-NaF, and given its higher sensitivity, there have been increasing applications in imaging. In this review, we will discuss the history, technical aspects, radiobiology, and biodistribution of this tracer. Finally, we compare the accuracy of 18F-NaF PET with other conventional imaging methods for detection of osseous metastasis.
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5.
The INTERNET STUDY: A phase II study of everolimus in patients with fluorodeoxyglucose (18 F) positron-emission tomography positive intermediate grade pancreatic neuroendocrine tumors.
Lung, MS, Hicks, RJ, Pavlakis, N, Link, E, Jefford, M, Thomson, B, Wyld, DK, Liauw, W, Akhurst, T, Kuru, N, et al
Asia-Pacific journal of clinical oncology. 2020;(3):150-157
Abstract
AIMS: This multicenter phase II trial evaluates the efficacy of everolimus in poor prognosis grade 2 (G2) pancreatic neuroendocrine tumors (PNETs), defined by 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) avidity. FDG-PET avidity in NETs is associated with a significantly higher risk of death, outperforming Ki-67 index or liver metastases as a poor prognostic factor. We hypothesized that everolimus has efficacy in patients with FDG-PET-avid G2 PNETs and prospectively evaluated progression-free survival (PFS) and response in the first-line setting. METHODS Patients with FDG-PET-avid G2 advanced PNET received everolimus 10 mg daily until disease progression. Patients were staged every 12 weeks with CT/MRI and FDG-PET and every 24 weeks with Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE, GaTate) PET. The primary endpoint was PFS at 6 months. Overall survival rate, PET/structural imaging response and toxicity were also measured. RESULTS Nine patients were accrued from December 2012 to February 2015. Median treatment duration was 13.8 months. The estimated PFS rate at 6 months was 78%. The best response on CT/MRI was stable disease in nine patients (100%) and partial response on FDG-PET in five patients (55.5%). Treatment-related adverse effects were consistent with previous studies of everolimus. CONCLUSION Everolimus is active with prolonged disease control in poor prognosis FDG-avid G2 PNETs. Treatment individualization based on functional imaging warrants further evaluation.
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6.
Copper-64-immunoPET imaging: bench to bedside.
Natarajan, A
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2020;(4):356-363
Abstract
Positron emission tomography (PET) is a growing non-invasive diagnostic and molecular imaging tool in nuclear medicine, that is used to identify several diseases including cancer. The immunoPET probe is made up of monoclonal antibodies (mAbs) or its fragments or similar molecules that tagged with positron radioisotopes (68Ga, 64Cu, 89Zr) bound together by a bifunctional chelator (BFC). This probe is designed to identify a specific disease. Currently, several immunoPET probes are being developed for preclinical as well as for clinical applications. These studies are showing promising results, both in preclinical and patients, using mostly 64Cu, 89Zr isotopes. This review elucidates the 64Cu based immunoPET applications, their pipelines and the emerging scope of this technique within the nuclear medicine and molecular imaging clinics from bench to bedside. Recently, immunoPET research have sharply increased especially after a big surge in approval of oncology antibodies by the FDA for immune checkpoint-blockade cancer immunotherapies. Currently, preclinical to clinical translations of immunoPET has several challenges, including designing probes, choice of radioisotopes, selection of stable BFC, and size of antibody and its tracer kinetics. All these obstacles will be addressed eventually by improving PET scanner sensitivity, designing appropriate size of imaging probe, and combining immunoPET with specific targeting antibodies. These improvements should contribute to the immunoPET becoming more applicable in clinics, which, in turn, will provide critical information for correct patient selection, for right dosing, and for the right time/staging of treatment.
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7.
18F-fluorodeoxyglucose use after cardiac transplant: A comparative study of suppression of physiological myocardial uptake.
Felix, RCM, Gouvea, CM, Reis, CCW, Dos Santos Miranda, JS, Schtruk, LBCE, Colafranceschi, AS, Mesquita, CT
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2020;(1):173-181
Abstract
BACKGROUND 18F-fluorodeoxyglucose (FDG) has been useful in the evaluation of myocardial inflammatory processes. However, it is challenging to identify them due to physiological 18F-FDG uptake. There are no publications demonstrating the application of FDG in post-transplant rejection in humans yet. The aim of this study is to determine the feasibility of suppression of myocardial FDG uptake in post-transplant patients, comparing three different protocols of preparation. METHODS Ten patients after heart transplantation were imaged by FDG associated with three endomyocardial biopsies (EMB), scheduled in the first year after the procedure. Before each imaging, patients were randomized to one of three preparations: (1) hyperlipidic-hypoglycemic diet; (2) fasting longer than 12 hours; and (3) fasting associated with intravenous heparin. All patients would undergo the three methods. FDG images were analyzed using visual analysis scores and relative radiotracer cardiac uptake (RRCU). RESULTS The suppression rate of radiotracer activity ranged from 55% to 62%. Visual analysis showed that preparation 3 presented less efficacy in the suppression compared to the others. However, RRCU did not show difference between the preparations. CONCLUSIONS Suppression of physiological myocardial FDG uptake after cardiac transplantation is feasible. The usefulness of heparin in the suppression is unclear.
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8.
Molecular Imaging in the Head and Neck: Diagnosis and Therapy.
Howard, BA
Radiologic clinics of North America. 2020;(6):1135-1146
Abstract
This article is a summary of the most up-to-date applications of radiopharmaceuticals to the diagnosis and therapy of benign and malignant diseases involving endocrine or neuroendocrine organs of the head and neck, focusing on radiotracers approved by the US Food and Drug Administration, such as I-123- and I-131-sodium iodide, F-18-fluorodeoxyglucose, Tc99m-sestamibi, as well as the more recently approved tracers Ga-68 DOTATATE and Lu-177 DOTATATE.
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9.
Clinical application of Fluciclovine PET, choline PET and gastrin-releasing polypeptide receptor (bombesin) targeting PET in prostate cancer.
Ceci, F, Castellucci, P, Polverari, G, Iagaru, A
Current opinion in urology. 2020;(5):641-648
Abstract
PURPOSE OF REVIEW The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA). RECENT FINDINGS Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface. SUMMARY Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.
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10.
Structural modifications of amino acid sequences of radiolabeled peptides for targeted tumor imaging.
Maleki, F, Farahani, AM, Rezazedeh, F, Sadeghzadeh, N
Bioorganic chemistry. 2020;:103802
Abstract
Molecular imaging techniques are increasingly being used in localization, staging and therapy control of cancer. Due to their unique target specificity for the endogenous receptors, radiopeptides have been used widely for the development of radiopharmaceuticals for targeted tumor imaging in nuclear oncology. It is necessary to modify radiolabeled peptides in order to achieve more effective agents. Structural modifications of amino acid chains have significant effect on the metabolic stability, biological activity and efficiency of peptide conjugates that are currently applied as imaging tracers. There are several ways to modify the peptide chain but the most common strategies include amino acid substitutions, cyclization and multimerization. In this review, we have focused on studies involving these kind of modifications on amino acid sequences of radiolabeled peptides and we have provided an overview of the effects of these chemical modifications on the in vitro and in vivo properties of these radioconjugates and their potential as SPECT (Single photon emission computed tomography) and PET (positron emission tomography) imaging agents.