L. T. Kim1, X. Tu2,3, Z. Han2,4,5, J. Wang2, W. Hui2, W. Chen2, H. Yuan2, Z. Li2, X. Sun4,5, X. Ma2,3, Z. Wu2 1University Of North Carolina At Chapel Hill, Division Of Surgical Oncology And Endocrine Surgery / Department Of Surgery, Chapel Hill, NC, USA 2University Of North Carolina At Chapel Hill, Biomedical Research Imaging Center, Department Of Radiology, Chapel Hill, NC, USA 3Guangdong Second Provincial General Hospital, Department Of Nuclear Medicine, Guangzhou, China 4Harbin Medical University, Molecular Imaging Research Center, Harbin, China 5Fourth Hospital of Harbin Medical University, Department Of Nuclear Medicine, Harbin, China
Introduction:
In the evaluation of patients with primary hyperparathyroidism, imaging is critical for patients undergoing directed parathyroidectomy and has become routine regardless of the operative approach. Current imaging techniques have several limitations in detecting normal and abnormal parathyroid glands. In this study, we describe the development of a new PET agent targeting the CaSR for parathyroid imaging.
Methods:
The introduction of 18F into BOC-protected Sensipar® (cinacalcet, a small molecule targeting the CaSR) was performed using direct photoredox C-H radiofluorination. For blocking experiments, Hcc827 cells (which have high CaSR expression) were incubated with [18F]F-ZW-cinacalcet, with or without excess amount of cinacalcet, CaCl2 or cold standard [19F]F-ZW-cinacalcet. In vivo PET scanning of rats was done with a SuperArgus Compact PET system. PET/CT was done in rats using a Sedecal Super Argus 4R PET/CT. For autoradiography, rats were injected with [18F]F-ZW-cinacalcet and sacrificed. Neck tissue including larynx, thyroid and parathyroid were excised and sectioned. Adjacent sections were used for autoradiography or immunohistochemistry.
Results:
Following synthesis, the final agent, [18F]F-ZW-cinacalcet, was obtained with >96% radiochemical purity and 4.6 Ci/µmol molar activity. When incubated with [18F]F-ZW-cinacalcet, the radio-activity uptake by Hcc827 cells increased over time. The uptake of [18F]F-ZW-cinacalcet was blocked by cold [19F]F-ZW-cinacalcet, cinacalcet and CaCl2. Using static PET, parathyroid could be detected early (0.5 h) post-injection of [18F]F-ZW-cinacalcet with a decrease to background levels at 2 h. Dynamic PET images of [18F]F-ZW-cinacalcet in rats were acquired for 60 minutes. [18F]F-ZW-cinacalcet accumulated into parathyroid quickly and peaked at about 7 min post-injection(p.i.) (0.33 ± 0.05 %ID/g), followed by a gradual decline to 0.17 ± 0.01 %ID/g at 60 min p.i.. Spatially oriented PET/CT images clearly discerned the parathyroid adjacent to the cricoid cartilage and trachea (fig A). Tracer uptake in parathyroid glands was significantly higher than that of the background tissues. Autoradiography confirmed co-localization of the [18F]F-ZW-cinacalcet tracer (fig B) and parathyroid tissue (fig C).
Conclusion:
In summary, we describe the synthesis of [18F]F-ZW-cinacalcet, and show that it specifically binds to the CaSR and is able to be detected in parathyroid glands in rat using PET/CT. The tracer shows excellent specificity over background tissue. Tissue kinetics in parathyroid shows rapid uptake and slow clearance. We conclude that [18F]F-ZW-cinacalcet is a promising agent for preoperative detection of parathyroid glands by PET/CT.
