Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine.

Dementia (the most common cause of Alzheimer's disease) is defined as a chronic or progressive syndrome with disturbance of multiple cortical functions, the most important of them including memory, learning capacity, comprehension, orientation, calculation, language, and judgement. These cognitive impairments affect the quality of life, behavior, and social relations. Techniques of nuclear medicine provide feasible ways to record the intracellular alterations of disease and deficiencies.

Optimal Indications of Radioimmunotherapy in Nuclear Medicine: A Mini-Review.

Immunotherapy has emerged as a very considerable and potent therapeutic method in which immune inhibitors have gained a lot of attention in the curative field of various cancers. Under certain circumstances, when radiotherapy is accompanied by immunotherapy, the efficacy of the therapeutic procedure increases. Irradiated tumor cells follow a pathway called immunogenic cell death, which targets tumor associated antigens.

The Future Direction of Women in Nuclear Medicine and Nuclear Medicine in Women's Health.

This work discusses the role of Nuclear Medicine for women's health, the role of women in the development of this emerging field and the various issues which arise from both. It emphasizes the importance of young women and their competing needs due to factors like pregnancy and work-related challenges. The objectives of this overview include improving imaging techniques, preserving fertility during cancer treatment, diagnosing pelvic and uterine conditions, developing radiopharmaceuticals for women's health, protecting female employees in Nuclear Medicine, and considering the role of artificial intelligence.

Recent Trends in Diagnostic Biomarkers of Tumor Microenvironment.

The tumor microenvironment (TME) play critical roles in tumor survival, progression, and metastasis and can be considered potential targets for molecular imaging of cancer. The targeting agents for imaging of TME components (e.g.

An Impressive Approach in Nuclear Medicine: Theranostics.

Radiometal-based theranostics or theragnostics, first used in the early 2000s, is the combined application of diagnostic and therapeutic agents that target the same molecule, and represents a considerable advancement in nuclear medicine. One of the promising fields related to theranostics is radioligand therapy. For instance, the concepts of targeting the prostate-specific membrane antigen (PSMA) for imaging and therapy in prostate cancer, or somatostatin receptor targeted imaging and therapy in neuroendocrine tumors (NETs) are part of the field of theranostics.

Theranostic Advances in Breast Cancer in Nuclear Medicine.

The implication of 'theranostic' refers to targeting an identical receptor for diagnostic and therapeutic purposes, by the same radioligand, simultaneously or separately. In regard to extensive efforts, many considerable theranostic tracers have been developed in recent years. Emerging evidence strongly demonstrates the tendency of nuclear medicine towards therapies based on a diagnosis.

Evaluation of Safety and Dosimetry of Lu-DOTA-ZOL for Therapy of Bone Metastases.

Palliative treatment of bone metastasis using radiolabeled bisphosphonates is a well-known concept proven to be safe and effective. A new therapeutic radiopharmaceutical for bone metastasis is Lu-DOTA-zoledronic acid (Lu-DOTA-ZOL). In this study, the safety and dosimetry of a single therapeutic dose of Lu-DOTA-ZOL were evaluated on the basis of a series of SPECT/CT images and blood samples.

Biodistribution and dosimetry of a single dose of albumin-binding ligand [Lu]Lu-PSMA-ALB-56 in patients with mCRPC.

Introduction: PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties.

Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA chelators.

Background: Fibroblast activation protein (FAP) is a proline selective serine protease that is overexpressed in tumor stroma and in lesions of many other diseases that are characterized by tissue remodeling. In 2014, a most potent FAP-inhibitor (referred to as UAMC1110) with low nanomolar FAP-affinity and high selectivity toward related enzymes such as prolyl oligopeptidase (PREP) and the dipeptidyl-peptidases (DPPs): DPP4, DPP8/9 and DPP2 were developed. This inhibitor has been adopted recently by other groups to create radiopharmaceuticals by coupling bifunctional chelator-linker systems.

DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis-Challenges and Critical Points in Implementation into Clinical Routine.

The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory requirements turned out to be unexpectedly challenging. The scope of this work is the presentation and discussion of problems encountered during this process.

Manual vs automated Ga-radiolabelling-A comparison of optimized processes.

A critical factor for clinical practice is the production of Ga radiopharmaceuticals manufactured manually or through an automated procedure. Ga radiopharmaceuticals are often prepared manually, although this method can lead to an increased operator's radiation dose and potential variability within production. The present work compares Ga-radiolabelling (PSMA-11; DOTA-TOC) utilizing a cassette module (GAIA; Elysia-Raytest; Germany) with a manual setup for routine clinical production with regard to process reliability and reproducibility.

Biodistribution and post-therapy dosimetric analysis of [Lu]Lu-DOTA in patients with osteoblastic metastases: first results.

Background: Preclinical biodistribution and dosimetric analysis of [Lu]Lu-DOTA suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [Lu]Lu-DOTA in patients with metastatic skeletal disease.

Method: Four patients with metastatic skeletal disease (age range, 64-83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.

Ethanol effects on Ga-radiolabelling efficacy and radiolysis in automated synthesis utilizing NaCl post-processing.

Objective: Recent studies showed that ethanol in the reaction mixture improves radiolabelling with trivalent radiometals in terms of precursor amount, reaction time, reaction temperature and radiolysis. With regard to clinical application, this effect is of practical interest in radiopharmacy. The aim of this study was to evaluate whether the positive effect of ethanol can be exploited in automated systems utilizing NaCl-post processing.

Preliminary results of biodistribution and dosimetric analysis of [Ga]Ga-DOTA: a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases.

Objective: Pre-clinical studies with gallium-68 zoledronate ([Ga]Ga-DOTA) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [Lu]Lu-DOTA and [Ac]Ac-DOTA. This study aims to be the first human biodistribution and dosimetric analysis of [Ga]Ga-DOTA.

Methods: Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190 MBq (4.

Improved Efficacy of Synthesizing *M-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study.

Typically, the synthesis of radiometal-based radiopharmaceuticals is performed in buffered aqueous solutions. We found that the presence of organic solvents like ethanol increased the radiolabeling yields of [Ga]Ga-DOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacatic acid). In the present study, the effect of organic cosolvents [ethanol (EtOH), isopropyl alcohol, and acetonitrile] on the radiolabeling yields of the macrocyclic chelator DOTA with several trivalent radiometals (gallium-68, scandium-44, and lutetium-177) was systematically investigated.

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

Unlabelled: In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma.

Methods: Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points.

Labeling of DOTA-conjugated HPMA-based polymers with trivalent metallic radionuclides for molecular imaging.

Background: In this work, the in vitro and in vivo stabilities and the pharmacology of HPMA-made homopolymers were studied by means of radiometal-labeled derivatives. Aiming to identify the fewer amount and the optimal DOTA-linker structure that provides quantitative labeling yields, diverse DOTA-linker systems were conjugated in different amounts to HPMA homopolymers to coordinate trivalent radiometals Me(III)* = gallium-68, scandium-44, and lutetium-177.

Results: Short linkers and as low as 1.

[44Sc]Sc-PSMA-617 Biodistribution and Dosimetry in Patients With Metastatic Castration-Resistant Prostate Carcinoma.

Aim: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients.

Clinical Translation and First In-Human Use of [Sc]Sc-PSMA-617 for PET Imaging of Metastasized Castrate-Resistant Prostate Cancer.

Background: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications.

Theranostics in nuclear medicine practice.

The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment.

Radioligand therapy of metastatic prostate cancer using Lu-PSMA-617 after radiation exposure to Ra-dichloride.

Radioligand therapy with Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of Lu-PSMA-617 after exposure to more cycles of Ra.

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer.

Unlabelled: Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load.

Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [Lu]Lu-PSMA-617.

Purpose: Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT.