A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer

Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes

Imaging of trigeminal neuralgia

Trigeminal neuralgia is one of the most frequent neuropathy of the cranial nerves, whose prevalence has been reported between 0.03% and 0.3% in the general population. This condition is a communal manifestation of several possible etiologies. The classical type of trigeminal neuralgia is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve, with no cause other than a neurovascular compression. Secondary trigeminal neuralgia is the term used to group a large amount of different diseases, which are alike in developing the symptoms of trigeminal neuralgia, due to an insult to the V CN which triggers the complex pathogenesis of pain. These conditions include inflammatory diseases, infections, neoplasms, autoimmune diseases, vascular diseases other than neurovascular conflict, and treatment-related disorders. Generally, the possible mechanisms which lead to the development of neuralgia include nerve distortion/compression by an external mass or damage to the nerve fibers due to an acute or chronic insult. The radiological investigation plays a pivotal role in the diagnosis of trigeminal neuralgia, and MRI constitutes the gold imaging standard in most cases. The trigeminal nerve is a mixed sensory-motor nerve which can be divided anatomically into five segments: brainstem segment, cisternal segment, Meckel’s cave segment, cavernous sinus segment, and extracranial segment. In this paragraph, an anatomy-based imaging approach is proposed to investigate the many causes of trigeminal neuralgia, highlighting the importance of choosing the appropriate sequences and parameters, in the light of a target-suited protocol