EC17 for Intraoperative Imaging for Parathyroidectomy

Primary hyperparathyroidism is a significant medical and public health problem in the world
and affects approximately 100,000 new patients in the United States alone. If left untreated
this can lead to renal stones, osteoporosis, fatigue, and depression. The best treatment for
primary hyperparathyroidism is surgical parathyroidectomy. However surgical parathyroidectomy
can be difficult due to the variant location of the parathyroid glands. Up to 5% of patients
leave the operating room without surgical cure.

Primary hyperparathyroidism is an ideal disease to investigate intraoperative fluorescent
imaging. This would allow surgeons to identify the parathyroid glands and resect the
suspicious parathyroid glands. Folate receptor (FR) has been found to be over-expressed in
parathyroid tissue and not thyroid issues. An ideal surgical treatment would combine
FR-specific fluorescent tracers with intraoperative imaging. It is important to note that FR
is expressed only in the proximal tubules of the kidneys, activated macrophages, and in the
choroidal plexus. Thus, the false positive detection rate is expected to be extremely low.

A group well known to us in the Netherlands has completed a pilot study utilizing a
folate-FITC conjugate in 12 patients with ovarian cancer. Another group of investigators in
Mayo have subsequently performed this study on 20 more patients without any serious adverse
events (personal communication). They report excellent sensitivity and specificity with this
technique with only grade 1 side effects (allergic reaction). All side effects reversed when
the injection was halted. Patients with a history of allergic reactions to insect bites
should not participate (fluorescein is derived from the firefly insect, folate is an
essential vitamin).

A fluorescent contrast agent (folate-FITC or EC17) will be used to determine if it will
localize to the primary tumor nodule(s) or mass(es) of patients undergoing parathyroid
surgery.