Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is β-amyloid peptide aggregates (Aβ). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aβ and important moments that led to the development of these tracers.

Over the last decade, an increasing number of studies have been published on the use of amyloid-β (Aβ) PET imaging with different ¹⁸F-radiopharmaceuticals for clinical characterization of Alzheimer’s disease (AD) in different stages. However, distinct study cohorts and different quantification techniques allow only for an indirect comparison between the different tracers. Thus, the aim of this study was the direct intra-individual in vivo comparison of different Aβ-targeted radiopharmaceuticals for PET imaging, including the newly developed agent [¹⁸F]FIBT. A small group of four animals of a well-characterized APP/PS1 transgenic (tg) mouse model of AD and gender-matched control (ctl) animals underwent a sequential and standardized PET imaging regimen for direct comparison of [¹⁸F]FIBT, [¹⁸F]florbetaben, and [¹¹C]PiB. The quantitative PET imaging data were cross-validated with the cerebral Aβ plaque load as quantified ex vivo on histological sections. We found that FIBT (2-(p-methylaminophenyl)-7-(2-[¹⁸F]fluoroethoxy)imidazo[2,1-b]benzothiazole) compares favorably to florbetaben as a high-contrasting PET radiopharmaceutical for imaging Aβ pathology. The excellent pharmacokinetics of FIBT in combination with its high-binding affinity towards Aβ resulted in feasible high-contrast imaging of Aβ with high global cortex to cerebellum standard uptake value ratio (SUVR) in 24-month-old tg mice (tg 1.68 ± 0.15 vs. ctl 0.95 ± 0.02). The SUVRs in transgenic versus control animals (SUVR_tg/SUVR_ctl) for FIBT (1.78 ± 0.16) were similar to the ratios as observed in humans (SUVR_AD/SUVR_ctl) for the established gold standard Pittsburgh compound B (PiB) (1.65 ± 0.41). This head-to-head PET tracer comparison study in mice indicated the good imaging properties of [¹⁸F]FIBT, such as high initial brain uptake, fast clearance of the brain, and high binding affinity towards Aβ as directly compared to the established amyloid tracers. Moreover, the preclinical study design is recommendable for reliable assessment and comparison of novel radiopharmaceuticals.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary and cancer. Inflammation in the brain is marked by the upregulation of translocator protein (TSPO) in microglia. High TSPO levels are also found, for example, in macrophages in cases of rheumatoid arthritis and in malignant tumor cells compared to their relatively low physiological expression. The same applies for cyclooxgenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable the monitoring of the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers, not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases such as rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown promising results against cancer, especially in recent years. However, pulmonary drug delivery of the predominantly hydrophobic photosensitizers still represents a significant obstacle. Nebulizing DPPC/Cholesterol liposomes loaded with the photosensitizer curcumin via a vibrating mesh nebulizer might overcome current restrictions. In this study, the liposomes were prepared by conventional thin-film hydration and two other methods based on dual centrifugation. The liposomes' physicochemical properties were determined before and after nebulization, showing that liposomes do not undergo any changes. However, morphological characterization of the differently prepared liposomes revealed structural differences between the methods in terms of lamellarity. Internalization of curcumin in lung adenocarcinoma (A549) cells was visualized and quantified. The generation of reactive oxygen species because of the photoreaction was also proven. The photodynamic efficacy of the liposomal formulations was tested against A549 cells. They revealed different phototoxic responses at different radiant exposures. Furthermore, the photodynamic efficacy was investigated after nebulizing curcumin-loaded liposomes onto xenografted tumors on the CAM, followed by irradiation, and evaluated using positron emission tomography/computed tomography and histological analysis. A decrease in tumor metabolism could be observed. Based on the efficacy of curcumin-loaded liposomes in 2D and 3D models, liposomes, especially with prior film formation, can be considered a promising approach for PDT against lung cancer.

Background: Prompt and accurate diagnosis of prostate cancer (PCa) is of paramount importance for effective treatment planning. While Gallium-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has proven efficacy in detecting PCa, limited availability poses challenges. As a potential alternative, [^99mTc]Tc-PSMA single photon emission computed tomography (SPECT)/computed tomography (CT) holds promise. This systematic review and meta-analysis aimed to evaluate the diagnostic value of [^99mTc]Tc-PSMA SPECT/CT for prostate cancer. Methods: A comprehensive search of PubMed, Cochrane, EMBASE, Scopus, Ovid, and Web of Science databases was conducted until July 2024. Sensitivity and specificity data were extracted to assess the diagnostic accuracy of [^99mTc]Tc-PSMA SPECT/CT, while the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate study quality. Statistical analyses were performed using STATA 18, with MetaDisc 1.4 employed to detect threshold effects. Diagnostic accuracy indicators, including sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (LR-), and positive likelihood ratio (LR+), were pooled. The area under the curve (AUC) of the combined model was calculated using summary receiver-operating characteristic (SROC) curves. Results: Seven studies meeting the inclusion criteria were identified from an initial pool of 1467 articles, with no publication bias observed. The pooled sensitivity, specificity, and AUC of [^99mTc]Tc-PSMA SPECT/CT were found to be 0.89 (95% CI, 0.84–0.93), 0.92 (95% CI, 0.67–0.99), and 0.93 (95% CI, 0.90–0.95), respectively. Additionally, the comprehensive diagnostic odds ratio, diagnostic score, positive likelihood ratio, and negative likelihood ratio were calculated as 95.24 (95% CI, 17.30-524.41), 4.56 (95% CI, 2.85–6.26), 11.35 (95% CI, 2.31–55.71), and 0.12 (95% CI, 0.08–0.18), respectively. Conclusions: In conclusion, our findings demonstrate that [^99mTc]Tc-PSMA SPECT/CT exhibits favorable diagnostic performance for prostate cancer and can provide valuable supplementary information, particularly in regions and settings where [⁶⁸Ga]Ga-PSMA PET/CT availability is limited, such as remote areas. These results highlight the potential of [^99mTc]Tc-PSMA SPECT/CT as a valuable tool in the diagnosis and management of prostate cancer, warranting further investigation and validation in larger patient cohorts.