ABSTRACT
BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.
Subject(s)
Adenoma, Oxyphilic , Iodine , Receptors, Thyrotropin , Thyroid Neoplasms , Animals , Humans , Male , Mice , Cell Line, Tumor , Iodine Radioisotopes , Mice, Nude , Positron-Emission Tomography/methods , Receptors, Thyrotropin/metabolism , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Thyrotropin , Tissue Distribution , Adenoma, Oxyphilic/diagnostic imaging , Adenoma, Oxyphilic/pathologyABSTRACT
BACKGROUND: Germicidal ultraviolet (UV-C) light has been shown as an effective modality for disinfection in laboratory settings and in the operative room. Traditionally, short-wavelength UV-C devices, which have previously been shown to cause DNA damage, are utilized only for disinfection in pre- and post-operative settings and are not continuously active during operations. Continuous use of intraoperative UV light has potential to decrease pathogens and subsequent surgical site infections (SSIs), which arise in approximately 5-15% of operative cases. SSIs are a significant determinant of patient morbidity, readmission rates, and overall cost. Therefore, a method of UV light disinfection with a low risk of DNA damage is needed so that greater antimicrobial protection can be afforded to patients during the entirety of their surgical procedures. A new disinfection device that harnesses longer-wavelength UV-A light to disinfect the surgical field throughout the entirety of the procedure, including pre- and post-operation has been developed. METHODS: This study aimed to determine if UV-A light administered intraoperatively was safe, as defined by the minimal presence of DNA damage and safe amounts of reflection upon medical personnel. Using in vitro models, we examined the differential impacts of UV-C and UV-A light on DNA damage and repair pathways. In a murine model, we looked at the production of DNA damage photoproduction in relation to UV-A versus UV-C exposure. RESULTS: Our results show UV-A light does not induce a significant amount of DNA damage at the cellular or tissue level. Furthermore, a preclinical porcine study showed that surgical personnel were exposed to safe levels of UV-A irradiance from an overhead UV-A light used during an operation. The amount of UV-A transmitted through surgical personal protective equipment (PPE) also remained within safe levels. CONCLUSIONS: In conclusion, we found that UV-A may be safe for intraoperative use.
