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Cerebral aneurysms and brain tumors are leading life-threatening diseases worldwide. By deliberately occluding the target lesion to reduce the blood supply, embolization has been widely used clinically to treat cerebral aneurysms and brain tumors. Conventional embolization is usually performed by threading a catheter through blood vessels to the target lesion, which is often limited by the poor steerability of the catheter in complex neurovascular networks, especially in submillimeter regions. Here, we propose magnetic soft microfiberbots with high steerability, reliable maneuverability, and multimodal shape reconfigurability to perform robotic embolization in submillimeter regions via a remote, untethered, and magnetically controllable manner. Magnetic soft microfiberbots were fabricated by thermal drawing magnetic soft composite into microfibers, followed by magnetizing and molding procedures to endow a helical magnetic polarity. By controlling magnetic fields, magnetic soft microfiberbots exhibit reversible elongated/aggregated shape morphing and helical propulsion in flow conditions, allowing for controllable navigation through complex vasculature and robotic embolization in submillimeter regions. We performed in vitro embolization of aneurysm and tumor in neurovascular phantoms and in vivo embolization of a rabbit femoral artery model under real-time fluoroscopy. These studies demonstrate the potential clinical value of our work, paving the way for a robotic embolization scheme in robotic settings. Editor's summary: As a minimally invasive treatment for aneurysms and brain tumors, surgeons typically insert a slender catheter through the femoral artery and guide it through blood vessels to deliver embolic agents. However, this method of embolization can be difficult to steer through complex vascular networks. A magnetic, soft microfiberbot was developed by Liuet al. to perform remotely controlled robotic embolization. The microfiberbot, composed of a magnetized fiber coiled into a helix shape, can conform to different vessel sizes and performs a corkscrew propulsion when subjected to an external magnetic field. The microfiberbots were used to successfully perform in vitro embolization of aneurysm and tumor in phantom blood vessels and in vivo embolization in a rabbit femoral artery. These proposed robots provide a controllable alternative to conventional catheter-based embolization. —Melisa Yashinski [ABSTRACT FROM AUTHOR]

Objective: Hepatocellular carcinoma (HCC) is a malignant tumor associated with high morbidity and mortality rates. In many non-prostate solid tumors such as HCC, prostate-specific membrane antigens (PSMA) are overexpressed in tumor-associated endothelial cells. Therefore, the aim of this study was to evaluate the performance of [68Ga]Ga-PSMA-617 PET imaging on HCC with different animal models, including cell line-derived xenografts (CDX) and patient-derived xenografts (PDX), and to explore its mechanisms of function. Methods: [68Ga]Ga-PSMA-617 was prepared. The expression level of PSMA in two human hepatocellular cancer cells (HepG2 and HuH-7) was evaluated, and the cellular uptakes of [68Ga]Ga-PSMA-617 were assayed. HepG2 and HuH-7 subcutaneous xenograft models, HepG2 orthotopic xenograft models, and four different groups of PDX models were prepared. Preclinical pharmacokinetics and performance of [68Ga]Ga-PSMA-617 were evaluated in different types of HCC xenografts models using small animal PET and biodistribution studies. Results: Low PSMA expression level of HepG2 and HuH-7 cells was observed, and the cellular uptake and blocking study confirmed the non-specificity of the PSMA-targeted probe binding to HepG2 and HuH-7 cells. In the subcutaneous xenograft models, the tumor uptakes at 0.5 h were 0.76 ± 0.12%ID/g (HepG2 tumors) and 0.78 ± 0.08%ID/g (HuH-7 tumors), respectively, which were significantly higher than those of the blocking groups (0.23 ± 0.04%ID/g and 0.20 ± 0.04%ID/g, respectively). In the orthotopic xenograft models, PET images clearly displayed the tumor locations based on the preferential accumulation of [68Ga]Ga-PSMA-617 in tumor tissue versus normal liver tissue, suggesting the possibility of using [68Ga]Ga-PSMA-617 PET imaging to detect primary HCC lesions in deep tissue. In the four different groups of HCC PDX models, PET imaging with [68Ga]Ga-PSMA-617 provided clear tumor uptakes with prominent tumor-to-background contrast, further demonstrating its potential for the clinical imaging of PSMA-positive HCC lesions. The staining of tumor tissue sections with CD31- and PSMA-specific antibodies visualized the tumor-associated blood vessels and PSMA expression on endothelial cells in subcutaneous, orthotopic tissues, and PDX tissues, confirming the imaging with [68Ga]Ga-PSMA-617 might be mediated by targeting tumor associated endothelium. Conclusion: In this study, in vivo PET on different types of HCC xenograft models illustrated high uptake within tumors, which confirmed that [68Ga]Ga-PSMA-617 PET may be a promising imaging modality for HCC by targeting tumor associated endothelium. [ABSTRACT FROM AUTHOR]