Laura Schäfer

Nanomedicines are increasingly employed in oncology. However, their efficacy is limited by heterogeneous nanoparticle accumulation in different tumors and patients. Nuclear imaging offers non‐invasive, patient‐ and lesion‐specific visualization and quantification of nanoparticle uptake, providing a biomarker to predict nanotherapy efficacy. We present a positron emission tomography (PET)‐imageable [mPEG‐ b ‐ p (HPMAm‐Bz)]‐based polymeric micelle platform for image‐guided and tumor‐targeted drug delivery, with potential for patient stratification and theranostics. Polymers with 1 or 3 deferoxamine (DFO) chelators were synthesized, and the corresponding micelles showed stable ⁸⁹ Zr‐radiolabeling and efficient drug (paclitaxel) encapsulation. PET imaging revealed long in vivo circulation times and high tumor accumulation, with more DFO per polymer accelerating drug release and increasing off‐target accumulation. Hence, single‐DFO‐containing polymers were used to develop companion diagnostic and paclitaxel‐loaded theranostic micelles. Both formulations displayed comparable biodistribution profiles and high levels of tumor uptake (>17% ID/g) and were able to capture inter‐ and intra‐individual heterogeneity in tumor targeting. Importantly, cryo‐preservation enables long‐term storage while maintaining in vivo performance and tumor‐targeting capabilities, bolstering translational potential. Taken together, DFO‐functionalized π‐electron‐stabilized micelles allow direct quantification of nanoparticle accumulation in tumors while mediating effective drug delivery, showing promise for patient stratification and as a theranostic platform for image‐guided and personalized cancer therapy.

Background: Radiolabeled fibroblast activation protein inhibitors (FAPIs) have emerged as novel radiopharmaceutical agents for tumor diagnosis. Compared with [¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), which reflects glucose uptake in metabolically active regions, FAPIs mainly bind to the fibroblast activation protein (FAP), which is highly expressed in tumor-associated fibroblasts, forming a pronounced signal. Several studies suggested potential superiority of FAPI tracers above [¹⁸F]FDG-based imaging in a variety of tumor entities. In this systematic review, we focus on the comparison of FAPI-PET/CT and [¹⁸F]FDG-PET/CT in upper-abdominal tumors. Methods: Original research published from 1 January 2021 to 22 December 2024 was collected from the PubMed and Web of Science databases (CRD42025648267). This research included only clinical studies, excluding conference abstracts and case reports. The risk of bias was assessed with the QUADAS-2 tool, and all evaluation steps performed independently by three independent reviewers. A systematic quality assessment of the included studies was conducted based on the imaging performance of FAPI-PET/CT and [¹⁸F]FDG-PET/CT for pancreatic, liver, and gastric cancers. The meta-analysis used relative risk (RR) as the effect size, with bias assessed via the Peters test (p-value > 0.05). Cochran’s Q test and I-squared value are used to comprehensively evaluate the magnitude of heterogeneity. Analyses and data visualization were performed in R language. Results: The database search identified 3272 articles. After screening, 31 studies were included in this analysis. The original studies enrolled 1377 participants (M/F: 850/527; ages predominantly between 50 and 70). Of these, 939 patients were ultimately diagnosed with tumors (five cancer subtypes) and included in this analysis. Meta-analysis results showed that FAPI-PET/CT significantly surpassed [¹⁸F]FDG-PET/CT in the detection of primary lesions (RRs = 1.20 and 1.17), lymph nodes (RRs = 1.18 and 1.24), distant metastases (RRs = 1.22 and 1.51), peritoneal metastases (RRs = 1.31 and 2.22), and bone metastases (RRs = 1.16 and 1.23). The two imaging methods exhibit clear differences in diagnostic performance (sensitivity: 98% vs. 79%; specificity: 83% vs. 87%), and FAPI-PET/CT demonstrates high and stable diagnostic performance (RRs = 1.20 and 1.17). Conclusions: Compared with [¹⁸F]FDG-PET/CT, FAPI-PET/CT demonstrates significant advantages in detecting primary lesions, lymph nodes, distant metastases, and peritoneal and bone metastases in pancreatic, liver, and gastric cancers (RR > 1.0). Overall, FAPI-PET/CT shows better diagnostic performance (RR > 1.0).

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a distinct type of stroke, primarily caused by the rupture of a brain aneurysm. The underlying mechanisms of aSAH remain incompletely understood, prompting ongoing research in this area. Recent investigations into the perivascular system revealed a distribution disturbance of the dye Alexa Fluor™ 594 during measurements. To further investigate this distribution anomaly, it is proposed to label the dye with a radionuclide for biokinetic tracking in rats by means of positron emission tomography for enhanced imaging and analysis. Results: The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide ⁶⁸Ga(III) in a no-carrier-added form. Initially, the NODA-GA-NHS ester was employed to react with the amino group of Alexa Fluor™ 594 1,5-diaminopentane, facilitating subsequent radiolabeling with ⁶⁸Ga. The formation of the Alexa Fluor™ 594-chelator conjugate, as well as the radiolabeling, were investigated as a function of reaction time and temperature. For potential animal experiments, it was necessary to increase the reaction temperature from room temperature to 80 °C to optimize the reaction conditions, given the short half-life of ⁶⁸Ga. Optimal labeling conditions were established, achieving a radiochemical yield of > 85%. Separation and purification of n.c.a. [⁶⁸Ga]Ga-NODA-GA-Alexa Fluor™ 594 were conducted, with impurities remaining below 3%. Conclusions: This experimental approach successfully yields the desired radiolabeled dye, which is now available for animal studies, potentially offering enhanced insight into the mechanisms of aSAH.

In this narrative review, we aim to summarize recent advancements in nuclear molecular imaging techniques and their applications in BCa management. The main focus of this review is on the most relevant clinical investigations from the past 2–3 years that highlight the enhanced diagnostic and therapeutic value of these imaging modalities. A variety of radiolabeled probes introduced in molecular imaging is explored, detailing their roles in the accurate diagnosis and characterization of BCa, as well as their integration into radioligand therapy and theragnostic strategies.

Small animal Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging techniques are crucial in preclinical cancer research, necessitating meticulous attention to radiotracer synthesis, quality assurance, and in vivo injection protocols. This study presents a comprehensive workflow tailored to enhance the robustness and reproducibility of small animal PET experiments. The synthesis process in the radiochemistry laboratory using 68Ga is detailed, highlighting stringent quality control and assurance protocols for each radiotracer production. Parameters such as concentration, molar activity, pH, and purity are rigorously monitored, aligning with standards applicable to human studies. This methodology introduces streamlined syringe preparation and a custom-designed 30G cannula for precise intravenous injections into mice. Monitoring of animal health during scanning, including temperature and heart rate, ensures their well-being throughout the procedure. Dosages for PET and SPECT scans are predetermined to balance data acquisition with minimizing radiation exposure to animals and researchers. Similarly, CT scans employ pre-programmed settings to limit radiation exposure, especially pertinent in long-term studies assessing treatment effects. By optimizing these steps, the workflow aims to standardize procedures, reduce variability, and enhance the quality of small animal PET/SPECT/CT imaging. This resource provides valuable insights for researchers seeking to improve the accuracy and reliability of preclinical investigations in molecular imaging, ultimately advancing the field.