Page 94 - Fluorescence-guided cancer surgery

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Chapter 6
DISCUSSION
Despite many preoperative imaging modalities, intraoperative identi cation and demarcation of paragangliomas can be challenging. Because complete surgical removal of the tumor is the only curative treatment option, real-time intraoperative imaging modalities which can assist in tumor identi cation are desperately needed. To the best of our knowledge, this is the rst report showing the intraoperative identi cation of paragangliomas using NIR uorescence imaging and MB in a clinical setting.
In the presented patient, the main lesion just caudal to the aortic bifurcation was clearly identi ed by CT, MRI, and MIBG-scan. CT also showed a cranially located smaller lesion, which was not identi ed by MRI or MIBG, and not recognized as a paraganglioma, probably due to its small size and/or lack of adequate tracer photon ux from small tumors3;10. Importantly, intraoperative identi cation of all tumors is of paramount importance for the complete surgical resection and thereby curative treatment. Although not identi ed by MRI or MIBG, the second, smaller, lesion was intensely uorescent and was con rmed histologically to be paraganglioma. In daily practice, there still is a discrepancy between identi cation of lesions during preoperative imaging and intraoperative recognition of these lesions, especially when they are smaller sized. Intraoperative NIRF imaging could potentially overcome this gap.
The pharmacokinetics of MB in the observed lesions are consistent with a perfusion e ect, but not for a retention e ect, because TBR decreases rapidly over time after initially high values. This makes the administration of MB for intraoperative identi cation of paragangliomas very useful for the direct identi cation of lesions, and apparently local metastases or second primary tumors.
Although the exact mechanism of MB accumulation in tumors and especially neuroendocrine tumors is mainly unclear, it has been described in several studies. Previous clinical studies show staining of neuroendocrine tumors and parathyroid adenomas using MB as a visible dye using high concentrations11-14 and with NIR uorescence imaging using low-dose MB7. Also in breast cancer, identi cation of tumors by NIR uorescence imaging using MB is described15. The mechanism behind this accumulation is based on physicochemical similarities between MB and sestamibi, a nuclear tracer used for MIBI-scans. Reports which describe the identi cation of paragangliomas using MIBI-scan