Fluorescence-guided detection of pituitary neuroendocrine tumor (PitNET) tissue during endoscopic transsphenoidal surgery available agents, their potential, and technical aspects

Abstract

Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future.

Modified low-dose second window indocyanine green technique improves near-infrared fluorescence image-guided dermatofibrosarcoma protuberans resection: A randomized control trial

“…Their results displayed that 12/15 gliomas were visualized with the NIRF imaging, with a sensitivity of 98% and specificity of 45% to confirm malignant areas in gadolinium-enhancing specimens. Similar results were later validated in brain metastases ( 24 ), pituitary adenomas ( 26 ), and intracranial meningiomas ( 21 ), pulmonary metastasectomy ( 23 ), breast lumpectomy ( 28 ) and other malignant tumors, in which the doses of ICG have varied between 5 mg/kg to 2.5 mg/kg. Newton et al ( 22 ) stratified patients by tumor histology and investigated the optimal dose of ICG in second window technique.…”

“…Hence, second window ICG (SWIG) technique based on the enhanced permeability retention (EPR) effect was put forward to improve tumor background ratios (TBRs) by altering the time and dose of ICG injection ( 18 , 19 ). Nowadays, SWIG approach of high-dose (2.5 mg/kg-5 mg/kg) ICG intravenous infused 24 h prior to surgery has been widely attempted in intraoperative NIRF imaging for identifying tumor margins or discriminating occult cancerous lesions ( 19 – 26 ).…”

Side-firing intraoperative ultrasound applied to resection of pituitary macroadenomas and giant adenomas: A single-center retrospective case-control study

“…Fluorescent label-based guidance may improve resection by selectively causing tumor tissue to fluoresce, assisting visualization and resection. Studies have shown conflicting results among the available fluorescent agents ( 19 , 29 ). Sodium fluorescein (FNa) and 5-ALA with laser-based optical biopsy are two agents that have been shown to selectively fluoresce adenomatous tissue; however, these results are not consistent across all studies ( 29 ).…”

“…Studies have shown conflicting results among the available fluorescent agents ( 19 , 29 ). Sodium fluorescein (FNa) and 5-ALA with laser-based optical biopsy are two agents that have been shown to selectively fluoresce adenomatous tissue; however, these results are not consistent across all studies ( 29 ). In a study specific to endoscopic endonasal skull base surgery, 5-ALA was ineffective for the identification of neoplastic pituitary adenoma tissue ( 19 ).…”

“…OTL38 binds to folate-expressing cells of non-functional adenomas and has greater photon tissue penetration than visible light fluorophores, allowing clearer demarcation between normal and neoplastic tissue ( 30 ). Although, this agent is still under investigation and more evidence is necessary to distinguish these agents as effective selective fluorescent agents to guide the resection of pituitary adenomas ( 29 , 30 ).…”