Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [18F]-FDG and NA [18F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of 11C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissues and organs. The radioisotopes typically used in SPECT imaging are iodine-123, technetium-99m, xenon-133, thallium-201, and indium-111. This systematic review article aims to clarify and disseminate the available scientific literature focused on PET/SPECT radiotracers and to provide an overview of the conducted research within the past decade, with an additional focus on the novel radiopharmaceuticals developed for medical imaging.

https://www.mdpi.com/1422-0067/23/9/5023/pdf?version=1652060133

Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade

Abstract: Magnetic iron oxide nanoparticles (magnetite and maghemite) are intensively studied due to their broad potential applications in medical and biological sciences. Their unique properties, such as nanometric size, large specific surface area, and superparamagnetism, allow them to be used in targeted drug delivery and internal radiotherapy by targeting an external magnetic field. In addition, they are successfully used in magnetic resonance imaging (MRI), hyperthermia, and radiolabelling. The appropriate design of nanoparticles allows them to be delivered to the desired tissues and organs. The desired biodistribution of nanoparticles, eg, cancerous tumors, is increased using an external magnetic field. Thus, knowledge of the biodistribution of these nanoparticles is essential for medical applications. It allows for determining whether nanoparticles are captured by the desired organs or accumulated in other tissues, which may lead to potential toxicity. This review article presents the main organs where nanoparticles accumulate. The sites of their first uptake are usually the liver, spleen, and lymph nodes, but with the appropriate design of nanoparticles, they can also be accumulated in organs such as the lungs, heart, or brain. In addition, the review describes the factors affecting the biodistribution of nanoparticles, including their size, shape, surface charge, coating molecules, and route of administration. Modern techniques for determining nanoparticle accumulation sites and concentration in isolated tissues or the body in vivo are also presented. Graphical Abstract: Keywords: magnetic nanoparticles, iron oxide nanoparticles, biodistribution, biodegradation 

In vivo Biodistribution and Clearance of Magnetic Iron Oxide Nanoparticles for Medical Applications

Biocompatible gold nanoparticles (AuNPs) are particularly interesting for photo-thermal therapy (PTT) of cancer treatment because of their ability to convert light into heating efficiently. Nevertheless, the random accumulation of AuNPs in tissues, mainly determined by their retention time in the bloodstream, is one of the main limiting factors for their use in PTT applications. For this reason, efficient targeting and monitoring of AuNPs in the selected tissues is of paramount importance. This manuscript reports on a new generation of 99m Tc-labeled AuNPs coated with keratin (Ker-AuNPs) and their spatial localization investigated by nuclear imaging techniques on an animal-free model. The effective radiolabeling of Ker-AuNPs with 99m Tc is achieved using the chelating agent diethylenetriaminepentaacetic acid (DTPA), resulting in the 99m Tc-DTPA-Ker-AuNPs nanoconjugate. The 99m Tc-DTPA-Ker-AuNPs display a radiochemical purity of 90.7% and excellent photo-thermal properties. In addition, the biocompatibility of the 99m Tc-DTPA-Ker-AuNPs with healthy human embryonic kidney (HEK293T) cells is shown. A Lab-On-a-Chip (LoC) approach is used to localize and study the stability of 99m Tc-DTPA-Ker-AuNPs under dynamic conditions. To this end, the nanoconjugates are injected into a polydimethylsiloxane microfluidic chip mimicking the renal filtering unit, the nephron, and monitored via radio-imaging and thermo-optical experiments. These detailed studies establish that DTPA-assisted 99m Tc-labeled Ker-AuNPs are excellent candidates as biocompatible and non-invasive radiolabeled nanotherapeutic for PTT-based applications. 

99mTc-labeled keratin gold-nanoparticles in a nephron-like microfluidic chip for photo-thermal therapy applications

Abstract Biomarker discovery and development are popular for detecting the subtle diseases. However, biomarkers are needed to be validated and approved, and even fewer are ever used clinically. Imaging biomarkers have a crucial role in the treatment of cancer patients because they provide objective information on tumor biology, the tumor's habitat, and the tumor’s signature in the environment. Tumor changes in response to an intervention complement molecular and genomic translational diagnosis as well as quantitative information. Neuro-oncology has become more prominent in diagnostics and targeted therapies. The classification of tumors has been actively updated, and drug discovery, and delivery in nanoimmunotherapies are advancing in the field of target therapy research. It is important that biomarkers and diagnostic implements be developed and used to assess the prognosis or late effects of long-term survivors. An improved realization of cancer biology has transformed its management with an increasing emphasis on a personalized approach in precision medicine. In the first part, we discuss the biomarker categories in relation to the courses of a disease and specific clinical contexts, including that patients and specimens should both directly reflect the target population and intended use. In the second part, we present the CT perfusion approach that provides quantitative and qualitative data that has been successfully applied to the clinical diagnosis, treatment and application. Furthermore, the novel and promising multiparametric MR imageing approach will provide deeper insights regarding the tumor microenvironment in the immune response. Additionally, we briefly remark new tactics based on MRI and PET for converging on imaging biomarkers combined with applications of bioinformatics in artificial intelligence. In the third part, we briefly address new approaches based on theranostics in precision medicine. These sophisticated techniques merge achievable standardizations into an applicatory apparatus for primarily a diagnostic implementation and tracking radioactive drugs to identify and to deliver therapies in an individualized medicine paradigm. In this article, we describe the critical principles for imaging biomarker characterization and discuss the current status of CT, MRI and PET in finiding imaging biomarkers of early disease. 

/pdf/imaging-biomarkers-for-clinical-applications-in-neuro-3a0w285u.pdf

Imaging biomarkers for clinical applications in neuro-oncology: current status and future perspectives

The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177-PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN).

Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer.

The remarkable amount of preclinical data achieved on 89Zr-PET imaging led to a significant clinical translation, concerning mainly immuno-PET applications. The aim of this systematic review is to provide a complete overview on clinical applications of 89Zr-PET imaging, using a systematic approach to identify and collect published studies performed in humans, sorted by field of application and specific disease subsections. A systematic literature search of articles suiting the inclusion criteria was conducted on Pubmed, Scopus, Central, and Web Of Science databases, including papers published from January 1967 to November 2020. Eligible studies had to be performed on humans through PET imaging with 89Zr-labeled compounds. The methodological quality was assessed through the Quality Assessment of Diagnostic accuracy Studies-2 tool. A total of 821 articles were screened. 74 studies performed on humans were assessed for eligibility with the exclusion of further 18, thus 56 articles were ultimately selected for the qualitative analysis. 89Zr has shown to be a powerful PET-imaging tool, in particular for radiolabeling antibodies in order to study antigen expression, biodistribution, anticancer treatment planning and follow-up. Other than oncologic applications, 89Zr-radiolabeled antibodies have been proposed for use in inflammatory and autoimmune disorders with interesting results. 89Zr-labeled nanoparticles represent groundbreaking radiopharmaceuticals with potential huge fields of application. To evaluate the clinical usefulness of 89Zr PET-imaging in different conditions and in real-world settings, and to widen its use in clinical practice, further translation of preclinical to clinical data is needed.

/pdf/89zr-pet-imaging-in-humans-a-systematic-review-53icbsnl3w.pdf

89Zr-PET imaging in humans: a systematic review

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.

https://www.mdpi.com/1422-0067/22/6/3036/pdf

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

https://link.springer.com/content/pdf/10.1007/s12350-020-02501-w.pdf

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

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89Zr-PET imaging in humans: a systematic review

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

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