Positron-emitting Radiopharmaceuticals Research Articles

Adverse reactions to positron-emitting radiopharmaceuticals

Adverse reactions to positron-emitting radiopharmaceuticals

PSMA PET/CT quick procedure guide

The application of PET/CT with radiopharmaceuticals targeting PSMA is significantly transforming the diagnostic and therapeutic strategies of patients with prostate cancer. In Spain, the availability and access to positron-emitting radiopharmaceuticals targeting Prostate-Specific Membrane Antigen (PSMA) have significantly changed in recent months. These changes are affecting their use in diagnostic procedures. As a result, its use within diagnostic protocols for patients with prostate cancer is undergoing significant modifications. In this collective and cooperative document, the authors have selected the most robust evidence accumulated to date to generate a clinical guide to achieve appropriate use of this technology. A format that presents the most frequent clinical situations and the patient profiles in which PSMA PET/CT plays a significant role or will do so in the immediate future has been chosen. It should be taken into account that regulatory restrictions mediate the current indications for its use in Spain, as well as its current cost and the production capacity of radiopharmaceuticals. The guideline presents a review of the established methodology for optimized imaging with each of the radiopharmaceutical variants targeting PSMA and recommendations for structured and accurate reporting of metabolic findings in combination with CT.

Diagnosis of Melanoma with 61Cu-Labeled PET Tracer.

Until the recent years, substances containing radioactive 61Cu were strongly considered as potential positron-emitting radiopharmaceuticals for use in positron emission tomography (PET) applications; however, due to their suitably long half-life, and generator-independent and cost-effective production, they seem to be economically viable for human imaging. Since malignant melanoma (MM) is a major public health problem, its early diagnosis is a crucial contributor to long-term survival, which can be achieved using radiolabeled α-melanocyte-stimulating hormone analog NAPamide derivatives. Here, we report on the physicochemical features of a new CB-15aneN5-based Cu(II) complex ([Cu(KFTGdiac)]-) and the ex vivo and in vivo characterization of its NAPamide conjugate. The rigid chelate possesses prompt complex formation and suitable inertness (t1/2 = 18.4 min in 5.0 M HCl at 50 °C), as well as excellent features in the diagnosis of B16-F10 melanoma tumors (T/M(SUVs) (in vivo): 12.7, %ID/g: 6.6 ± 0.3, T/M (ex vivo): 22).

Impact of PET/CT Imaging with FDG in Locally Advanced Cervical Carcinoma-A Literature Review.

Positron emission tomography (PET) and computed tomography (CT) have evolved as a pivotal diagnostic modality in the field of oncology. With its increasing application in staging and ready availability, it becomes imperative for committed radiation oncologists to possess a complete analysis and understanding of integration of molecular imaging, which can be helpful for radiation planning, while also acknowledging its possible limitations and challenges. A significant obstacle lies in the synthesis and design of tumor-specific bmolecules for diagnosing and treating cancer. The utilization of radiation in medical biochemistry and biotechnology, encompassing diagnosis, therapy, and control of biological systems, is encapsulated under the umbrella term "nuclear medicine". Notably, the application of various radioisotopes in pharmaceutics has garnered significant attention, particularly in the realm of delivery systems for drugs, DNA, and imaging agents. The present article provides a comprehensive review of use of novel techniques PET and CT with major positron-emitting radiopharmaceuticals currently in progress or utilized in clinical practice with their integration into imaging and radiation therapy.

Improvement of phoswich detector-based β+/γ-ray discrimination algorithm with deep learning.

Positron probes can accurately localize malignant tumors by directly detecting positrons emitted from positron-emitting radiopharmaceuticals that accumulate in malignant tumors. In the conventional method for direct positron detection, multilayer scintillator detection and pulse shape discrimination techniques are used. However, some γ-rays cannot be distinguished by conventional methods. Accordingly, these γ-rays are misidentified as positrons, which may increase the error rate of positron detection. To analyze the energy distribution in each scintillator of the multilayer scintillator detector to distinguish true positrons and γ-rays and to improve the positron detection algorithm by discriminating true and false positrons. We used Autoencoder, an unsupervised deep learning architecture, to obtain the energy distribution data in each scintillator of the multilayer scintillator detector. The Autoencoder was trained to separate the combined signals generated from the multilayer scintillator detector into two signals of each scintillator. An energy window was then applied to the energy distribution obtained using the trained Autoencoder to distinguish true positrons from false positrons. Finally, the performance of the proposed method and conventional positron detection algorithm was evaluated in terms of the sensitivity and error rate for positron detection. The energy distribution map obtained using the trained Autoencoder was proven to be similar to that of the simulated results. Furthermore, the proposed method demonstrated a 29.79% (+0.42%p) increase in positron detection sensitivity compared to the conventional method, both having an equal error rate of 0.48%. However, when both methods were set to have the same sensitivity of 1.83%, the proposed method had an error rate that was 25.0% (-0.16%p) lower than that of the conventional method. We proposed and developed an Autoencoder-based positron detection algorithm that can discriminate between true and false positrons with a smaller error rate than conventional methods. We verified that the proposed method could increase the positron detection sensitivity while maintaining a low error rate compared to the conventional method. If the proposed algorithm is implemented in handheld positron detection probes or cameras, diseases such as cancers can be more accurately localized in a shorter time compared with using traditional methods.

Abstract P2-09-01: An Emerging Technology for Breast Cancer Detection - Preliminary Data of Breast Cancer Detection using Novel Low Dose Positron Emission Mammography

Abstract Purpose: To investigate the feasibility of low-dose Positron Emission Mammography (PEM) to identify breast cancer. Materials and Methods: In an REB-approved ongoing clinical trial, which started in December 2019, all newly diagnosed women with breast cancer who had not undergone neoadjuvant chemotherapy and consented to the study were randomly assigned independently of their mammographic breast density, tumor size, and histopathology cancer subtype to perform PEM using a novel organ-targeted PET system(Radialis PET Imager, Radialis Inc., FDA cleared to image and measure the distribution of injected positron-emitting radiopharmaceuticals) with either 1mCi, 2mCi or 5 mCi of 18F-FDG. The PEM images acquired 1 and 4 hours after 18F-FDG administration were reviewed in consensus by two fellowship-trained breast radiologists blinded to cancer location. PEM imaging features of known malignancies and additional PEM findings were recorded and correlated with histopathology as the ground truth. Results: Our cohort comprised 22 women with a median age of 51 years (range 32-85) with 88 completed bilateral sets of images where 23 cancers (18 invasives, and 5 in situ) were present. The median invasive cancer size on surgical pathology was 28 mm (range: 3-120). Out of 18 invasive cancers, the only PEM images that did not visualize cancer (2 invasive lobular cancers and 2 in-situ cancers) were acquired with the lowest dose of 18F-FDG (1 mCi). A total of 6 (27.3%) subjects received 1mCi 18F-FDG with 5 invasive cancers, 7 (31.8%) of patients received 5 mCi 18F-FDG with 7 invasive cancers, and 9 (40.9%) of patients received 5 mCi 18F-FDG with 6 invasive cancers. A total of 3 false-positive images of benign findings were also present. No additional cancers were identified exclusively by PEM. The PEM performance was similar following an additional 3-hour interval for radiotracer uptake. Conclusion: This preliminary data results show the feasibility of invasive breast cancer detection with a decreased 18F-FDG dose, possibly due to the novel PEM system detectors increasing the sensitivity to radiotracer and the perceived spatial resolution by the visual assessment. Larger-scale clinical trials are required to consolidate our preliminary findings. Clinical Relevance: A novel organ-targeted PET system enables the detection of invasive breast cancer using low-dose PEM, potentially emerging as a promising novel imaging tool. Citation Format: Vivianne Freitas, Michael L. Waterston, Ken O. Olsen, Oleksandr Bubon, Shayna Parker, Brandon Baldassi, Borys Komarov, Samira Taeb, Alla Reznik. An Emerging Technology for Breast Cancer Detection - Preliminary Data of Breast Cancer Detection using Novel Low Dose Positron Emission Mammography [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-09-01.

Diagnostic accuracy of F-18-Fluorocholine PET/CT and multiparametric MRI for prostate cancer.

BackgroundPositron emission tomography (PET) using different positron-emitting radiopharmaceuticals has emerged as a promising new metabolic diagnostic tool for the evaluation of a variety of malignant diseases. Thus, we investigated the diagnostic efficacy of F-18-Fluorocholine positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) for the detection and localization of tumors within the prostate with the correlating histopathology as the standard of reference.MethodsForty patients with histologically proven prostate cancer underwent both F-18-Fluorocholine PET/CT and mpMRI before robot-assisted laparoscopic radical prostatectomy (RARP). The maximum standard uptake values and the tumor-to-background ratio were measured on a sextant basis. In brief, the sextants were defined as right apex, right middle, right base, left apex, left middle, and left base. For each tumor region, the correlation of the tumor localization based on the sextant in both F-18-Fluorocholine PET/CT and mpMRI scans with the histopathological results was determined.ResultsThe correlation between both imaging modalities and RARP pathology representing (1) all cancer and (2) clinically significant cancer defined as a ≥ International Society of Urological Pathology grade of 2 showed that the sensitivity and the area under the curve (AUC) were higher for mpMRI than for F-18-Fluorocholine PET/CT. In contrast, F-18-Fluorocholine PET/CT had relatively higher specificity than mpMRI. Importantly, we found a very high AUC value of over 0.8 in both imaging modalities.ConclusionmpMRI had results superior to F-18-Fluorocholine PET/CT in assessing intraprostatic tumor localization. However, F-18-Fluorocholine PET/CT showed superiority in terms of specificity. Thus, using both modalities in conjunction could provide better treatment planning.

English

BACKGROUND PET-CT is an imaging modality which electronically detects positron-emitting radiopharmaceuticals in the human body and reveals its exact anatomical location.1 PET CT measures the metabolic and functional activity of living tissue noninvasively.1 This technology is utilized in diagnosis, planning treatment and predicting outcomes in various neurological conditions.1 Depending upon various patterns of FDG uptake in different parts of brain, 18FDG PET-CT allows us to differentiate between various types of dementia.2 PET CT allows tracking the course of disease and revealing the severity of the disease.2 In this article, we discuss the imaging findings of normal 18 FDG PET-CT of brain and 8 different neurological conditions with their corresponding brain PET-CT findings. METHODS To study the role of 18FDG-PET/CT in neurological conditions, we identified 8 different patients who underwent 18FDG-PET/CT imaging of brain for clinically suspected different neurological diseases at Department of Radiodiagnosis-Centre of Excellence (CERIS), SRIHER, Chennai, between 2015 and 2019. Siemens Biograph Horizon 16-slice PET/CT scanner with TrueV was used. Syngo.Via Version VB30A software was used. 18F- Fluorodeoxyglucose was the radiotracer used [Dose: 3-7 mCi]. After the scan, different patterns of 18 FDG uptake in the brain were analyzed in each of these patients. RESULTS 18 FDG PET-CT showed reduced uptake in the epileptogenic foci in the brain. Alzheimer’s disease showed decreased FDG uptake in bilateral precuneus, posterior cingulate region, parietal cortex and frontal cortex. Fronto-temporal dementia revealed reduced FDG uptake in anterior cingulate gyrus and anterior temporal lobe. Primary progressive aphasia showed asymmetrical reduced metabolic activity in the bilateral frontal and temporal lobes. Progressive supranuclear palsy revealed reduced metabolic activity in bilateral paramedian frontal region, head of caudate nuclei and midbrain; Multi systemic atrophy showed reduced metabolic activity in midbrain, pons, medulla oblongata and the cerebellum; AIDS related dementia showed global hypometabolism with preserved uptake in basal ganglia. CONCLUSIONS 18FDG-PET/CT has a vital complementary role in the evaluation CNS disorders along with clinical examination, other imaging modalities like CT, MRI, and electroencephalogram (EEG). Radiologists should be aware of these different patterns of FDG uptake to aid the clinical diagnosis and early treatment. KEY WORDS 18 FDG PET-CT, 18FDG Uptake, Hypometabolism, PET-CT Brain

The current role of PET/CT in urological malignancies

In the past decade, there has been significant progress in the field of Nuclear Medicine in the diagnostic evaluation of urological malignancies, mainly because of the technological advance in PET/CT scanners and the increasing variety of positron-emitting radiopharmaceuticals such as 18F-FDG, 68Ga-PSMA, 18F-PSMA, 18F-sodium fluoride, and others. However, urological imaging with radiotracers is still challenging due to the biodistribution and normal urinary excretion of these tracers, requiring expertise in diagnostic imaging. The purpose of this review was to evaluate the current role of PET/CT imaging in urological malignancies. In this non-systematic review, we will discuss the current role of radiotracers for PET/CT imaging in the prostate, bladder, renal and testicular cancers based on the most recent and relevant publications and current guidelines. Furthermore, we will address imaging techniques to overcome the difficulty in PET/CT urological imaging in order to increase lesion detectability. PET/CT images are useful for staging locoregional and distant metastases, restaging/detecting recurrence, evaluating response to therapy, and, in some urological malignancies, may be used as a prognostic indicator. Furthermore, PET/CT images play an increasing role in Theranostics by evaluating patients requiring treatment of bone pain resulting from osteoblastic metastases as well as treatment of metastases from prostate cancer, promoting survival benefits. PET/CT imaging has an established role in the diagnosis of some urological malignancies and, in specific clinical indications, is used because of the enormous potential to alter patient management. Besides the established roles of FDG PET/CT, the advances of novel radiotracers for PET/CT imaging in urological malignancies, such as PSMA PET/CT, allows evaluation in the settings of staging, recurrence, response to therapy, and prognosis. Furthermore, PET/CT imaging helps in planning and assessing response to treatment in theranostics. Molecular images identify early changes that conventional anatomical studies cannot, and for this reason, the images performed on PET/CT are becoming increasingly indispensable in specific clinical situations and with precise indications according to the type of urological malignancy.

Frontispiece: Chemical Kinetics of Radiolabelling Reactions

Chemical kinetics is one of the most powerful tools available for investigating reaction mechanisms, but is rarely applied in radiopharmaceutical sciences. The Concept article by J. P. Holland on page 16472 ff. introduces the theoretical basis of radiochemical kinetics and illustrates how kinetic modelling can be used to aid in the design, discovery and optimisation of radiolabelling reactions for the synthesis of positron-emitting radiopharmaceuticals. Examples show kinetic simulations of complex reaction mixtures including the synthesis of a diverse range of clinical grade radiopharmaceuticals like [11C]raclopride, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG), [68Ga]GaPSMA-11, and the antibody-based agent [89Zr]Zr-DFO-J591.

Cardiac Radionuclide Imaging in Rodents: A Review of Methods, Results, and Factors at Play.

The interest around small-animal cardiac radionuclide imaging is growing as rodent models can be manipulated to allow the simulation of human diseases. In addition to new radiopharmaceuticals testing, often researchers apply well-established probes to animal models, to follow the evolution of the target disease. This reverse translation of standard radiopharmaceuticals to rodent models is complicated by technical shortcomings and by obvious differences between human and rodent cardiac physiology. In addition, radionuclide studies involving small animals are affected by several extrinsic variables, such as the choice of anesthetic. In this paper, we review the major cardiac features that can be studied with classical single-photon and positron-emitting radiopharmaceuticals, namely, cardiac function, perfusion and metabolism, as well as the results and pitfalls of small-animal radionuclide imaging techniques. In addition, we provide a concise guide to the understanding of the most frequently used anesthetics such as ketamine/xylazine, isoflurane, and pentobarbital. We address in particular their mechanisms of action and the potential effects on radionuclide imaging. Indeed, cardiac function, perfusion, and metabolism can all be significantly affected by varying anesthetics and animal handling conditions.

ORGAN DOSES AND EFFECTIVE DOSE FOR FIVE PET RADIOPHARMACEUTICALS.

Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.

Chapter 11 - Positron Emission Tomography

Positron emission tomography (PET) is a minimally invasive imaging procedure with a wide range of clinical and research applications. PET allows for the three-dimensional mapping of administered positron-emitting radiopharmaceuticals such as (18)F-fluorodeoxyglucose (for imaging glucose metabolism). PET enables the study of biologic function in both health and disease, in contrast to magnetic resonance imaging (MRI) and computed tomography (CT), that are more suited to study a body's morphologic changes, although functional MRI can also be used to study certain brain functions by measuring blood flow changes during task performance. This chapter first provides an overview of the basic physics principles and instrumentation behind PET methodology, with an introduction to the merits of merging functional PET imaging with anatomic CT or MRI imaging. We then focus on clinical neurologic disorders, and reference research on relevant PET radiopharmaceuticals when applicable. We then provide an overview of PET scan interpretation and findings in several specific neurologic disorders such as dementias, epilepsy, movement disorders, infection, cerebrovascular disorders, and brain tumors.

18F-Fluoride PET in the Assessment of Malignant Bone Disease.

In the 1970s, 18F-labeled sodium fluoride (18F-NaF), one of the most ubiquitous positron-emitting radiopharmaceuticals, was briefly used for skeletal scintigraphy before the introduction of 99mTc-labeled diphosphonates with optimal characteristics for conventional γ cameras ([1][1],[2][2]). 18F-NaF

Calculation of Positron Distribution in the Presence of a Uniform Magnetic Field for the Improvement of Positron Emission Tomography (PET) Imaging Using GEANT4 Toolkit

Introduction Range and diffusion of positron-emitting radiopharmaceuticals are important parameters for image resolution in positron emission tomography (PET). In this study, GEANT4 toolkit was applied to study positron diffusion in soft tissues with and without a magnetic field for six commonly used isotopes in PET imaging including 11C, 13N, 15O, 18F, 68Ga, and 82Rb. Materials and Methods GEANT4 toolkit was used to simulate the transport and interactions of positrons. Calculations were performed for the soft tissue phantom (8 mm ×8 mm × 8 mm). Positrons were emitted isotropically from the center of the phantom. By the application of a magnetic field perpendicular to the path of positrons, lateral scattering of positrons could be prevented due to Lorentz force. When the positron energy was below the cut-off threshold (0.001 MeV), the simulation was terminated. Results The findings showed that the presence of a magnetic field increased the rate of positron annihilation. At magnetic field strengths of 3, 7, and 10 Tesla, 18F with the lowest decay energy showed improvements in the ratio of full width at half maximum (FWHM) resolution to the peak of curve by 3.64%, 3.89%, and 5.96%, respectively. In addition, at magnetic field strengths of 3, 7 and 10 Tesla, 82Rb with the highest decay energy showed improvements in resolution by 33%, 85%, and 99%, respectively. Conclusion Application of a magnetic field perpendicular to the positron diffusion plane prevented the scattering of positrons, and consequently, improved the intrinsic spatial resolution of PET imaging, caused by positron range effects.

Microwave-assisted radiosynthesis of the hypoxia marker 1-α-D-(5- deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole ([18F]FAZA).

The routine manufacture of most short-lived positron-emitting radiopharmaceuticals (PERs) involves conventional heating to accelerate the radiolabeling process. Nucleophilic radiofluorination reactions are generally slow at lower temperatures, and are accompanied by thermal decomposition of both precursor and product at higher temperatures. This necessitates HPLC purification and results in lower recovered radiochemical yields (rRCYs). [(18)F]FAZA, a PER for clinical imaging of focal tissue hypoxia, is routinely manufactured in-house in 3-12% rRCY using a Health Canada approved conventional heating procedure. The microwave-assisted (MW) radiosynthesis of [(18)F]FAZA is now reported. Manual (MRDS) and automated (ASU) reagent delivery systems coupled to a commercial MW unit were built in-house. The MW unit controlled power, irradiation time and monitored reaction temperature (Tmax control), while the acetylAZA tosylate precursor and QMA Accel(TM) cartridge eluent reagents (K2CO3, K2.2.2) were dispensed by the MRDS or ASU. The radiofluorination yields (RFYs) and the chemical and radiochemical TLC profiles of the post-labeling reaction mixtures were compared to those obtained using the conventional heating production method and to those reported for optimized literature methods. MW RFYs for [(18)F]FAZA reached >76% (n=3) in 3 min. Post-labeling analysis of the MW-assisted reaction mixtures demonstrated cleaner UV and radiochemical TLC profiles than those obtained from conventional heating in routine production runs; the relatively clean MW reactions allowed rapid HPLC isolation of [(18)F]FAZA in overall rRCYs of 55±4%. In practical terms, the MW process provided only small gains in reaction time and RFY, but produced only a few secondary impurities, thereby improving the rRCY in comparison to conventional heating methods. These findings provide a rationale for adaptation of the MW-assisted method for the routine production of clinical [(18)F]FAZA.

Optimization of nucleophilic ¹⁸F radiofluorinations using a microfluidic reaction approach.

Microfluidic techniques are increasingly being used to synthesize positron-emitting radiopharmaceuticals. Several reports demonstrate higher incorporation yields, with shorter reaction times and reduced amounts of reagents compared with traditional vessel-based techniques. Microfluidic techniques, therefore, have tremendous potential for allowing rapid and cost-effective optimization of new radiotracers. This protocol describes the implementation of a suitable microfluidic process to optimize classical (18)F radiofluorination reactions by rationalizing the time and reagents used. Reaction optimization varies depending on the systems used, and it typically involves 5-10 experimental days of up to 4 h of sample collection and analysis. In particular, the protocol allows optimization of the key fluidic parameters in the first tier of experiments: reaction temperature, residence time and reagent ratio. Other parameters, such as solvent, activating agent and precursor concentration need to be stated before the experimental runs. Once the optimal set of parameters is found, repeatability and scalability are also tested in the second tier of experiments. This protocol allows the standardization of a microfluidic methodology that could be applied in any radiochemistry laboratory, in order to enable rapid and efficient radiosynthesis of new and existing [(18)F]-radiotracers. Here we show how this method can be applied to the radiofluorination optimization of [(18)F]-MEL050, a melanoma tumor imaging agent. This approach, if integrated into a good manufacturing practice (GMP) framework, could result in the reduction of materials and the time required to bring new radiotracers toward preclinical and clinical applications.

Multiagent targeting of neuroendocrine neoplasms

In the field of nuclear medicine, multiagent imaging can disclose enhanced expression of specific target molecules of neoplastic cells. This molecular information can be combined with the information provided by anatomical imaging. Over the past 20 years the use of radiolabeled somatostatin analogs as high-affinity tracers binding specifically to somatostatin receptors has allowed successful molecular imaging of neuroendocrine neoplasms (NENs), initially with single-photon-emitting radiopharmaceuticals, and subsequently also with positron-emitting radiopharmaceuticals. In this context, whole-body somatostatin receptor scintigraphy has changed the diagnostic and therapeutic approach to patients with NENs; moreover, somatostatin analog positron emission tomography (PET) tracers that allow higher spatial resolution imaging have recently been introduced. Nevertheless, several NENs can also be successfully imaged with radioagents that target the catecholamine pathway. Although radioiodinated meta-iodobenzylguanidine (MIBG) is traditionally the first option for radionuclide imaging and treatment of these NENs, the use of PET with 18F-l-dihydroxyphenylalanine is being increasingly reported, this approach showing several advantages over conventional imaging. Moreover, changes in tumor biology can be characterized by modifications in receptor or transporter expression on the cell membrane, and evidence has recently emerged that NENs expressing glucose transporters are more aggressive than tumors with low expression of glucose transporters. Therefore, [18F]FDG PET could provide prognostic information useful for stratifying patients according to their risk and for planning the correct therapy. The identification of new radiopharmaceuticals specific for different targets will constitute the basis not only of new diagnostic imaging approaches, but also of new therapeutic applications in NENs, besides radiolabeled peptide receptor radionuclide and 131I-MIBG therapy.

When to perform positron emission tomography/computed tomography or radionuclide bone scan in patients with recently diagnosed prostate cancer

Skeletal metastases are very common in prostate cancer and represent the main metastatic site in about 80% of prostate cancer patients, with a significant impact in patients’ prognosis. Early detection of bone metastases is critical in the management of patients with recently diagnosed high-risk prostate cancer: radical treatment is recommended in case of localized disease; systemic therapy should be preferred in patients with distant secondary disease. Bone scintigraphy using radiolabeled bisphosphonates is of great importance in the management of these patients; however, its main drawback is its low overall accuracy, due to the nonspecific uptake in sites of increased bone turnover. Positron-emitting radiopharmaceuticals, such as fluorine-18-fluorodeoxyglucose, choline-derived drugs (fluorine-18-fluorocholine and carbon-11-choline) and sodium fluorine-18-fluoride, are increasingly used in clinical practice to detect metastatic spread, and particularly bone involvement, in patients with prostate cancer, to reinforce or substitute information provided by bone scan. Each radiopharmaceutical has a specific mechanism of uptake; therefore, diagnostic performances may differ from one radiopharmaceutical to another on the same lesions, as demonstrated in the literature, with variable sensitivity, specificity, and overall accuracy values in the same patients. Whether bone scintigraphy can be substituted by these new methods is a matter of debate. However, greater radiobiological burden, higher costs, and the necessity of an in-site cyclotron limit the use of these positron emission tomography methods as first-line investigations in patients with prostate cancer: bone scintigraphy remains the mainstay for the detection of bone metastases in current clinical practice.

Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI) using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.