Team Science in Surgical Oncologic Care
CME
Lawrence Kim, MD, FACS, FACE
Professor
University of North Carolina at Chapel Hill
Chapel Hill, NC, United States
Disclosure(s): No financial relationships to disclose
tu xianshuang, PhD
Postdoctoral fellow
University of North Carolina, United States
Disclosure information not submitted.
Han Zhaoguo, MD
Postdoctoral fellow
University of North Carolina, United States
Disclosure information not submitted.
Mia MacDonald, MD
Resident
University of North Carolina, United States
Disclosure(s): No financial relationships to disclose
Mia MacDonald, MD
Resident
University of North Carolina, United States
Disclosure(s): No financial relationships to disclose
Wang Jason, MS
Research Associate
University of North Carolina, United States
Disclosure information not submitted.
Hui Wang, PhD
Research Associate
University of North Carolina, United States
Disclosure information not submitted.
Wei Chen, PhD
Postdoctoral fellow
University of North Carolina, United States
Disclosure information not submitted.
Hong Yuan, PhD
Professor
University of North Carolina, United States
Disclosure information not submitted.
Zibo Li, PhD
Professor
University of North Carolina, United States
Disclosure information not submitted.
Xilin Sun, MD
Professor
Harbin Medical University, Harbin, China, United States
Disclosure information not submitted.
Xiaofen Ma, MD
Professor
Guangdong Second Provincial General Hospital. Guangzhou, China, United States
Disclosure information not submitted.
Zhanhong Wu, PhD
Associate Professor
University of North Carolina, United States
Disclosure information not submitted.
In vivo static PET/CT scans were performed on rats at 0.5h, 1h, 2h post-injection with [18F]F-ZW-cinacalcet . The rats were sacrificed and ex vivo autoradiography and immunohistochemistry (IHC) were performed on the larynx, thyroid, and parathyroid tissues to verify the accuracy of the radiotracer as seen on PET/CT. Dynamic PET/MRI in non-human primates (NHP, rhesus macaques) was performed under sedation immediately after injection. A static PET/MRI was performed 2h post-injection. Toxicity studies were performed in JAX Swiss outbred mice.
Results: Static PET/CT of rats demonstrated parathyroid detection at 0.5h post-injection with a decrease to background levels at 2h. Dynamic PET images of rats were acquired for 60 minutes, with [18F]F-ZW-cinacalcet accumulating quickly in parathyroid, peaking at 7 min post-injection (0.33 ± 0.05 %ID/g), followed by a gradual decline to 0.17 ± 0.01 %ID/g at 60 min post-injection. 3D PET/CT images clearly discerned the parathyroid adjacent to the cricoid cartilage and trachea. The uptake of radiotracer and CaSR expression in parathyroid were significantly higher than in thyroid background tissues (P < 0.01), with parathyroid/thyroid ratios of 6.60 ± 1.28 in autoradiography and 3.76 ± 1.13 in IHC staining. CaSR expression level correlated well with radiotracer uptake (r = 0.93, 95% confidence interval 0.46~0.99, R2=0.86) in the parathyroid and thyroid. In the NHPs, dynamic PET/MRI showed peak thyroid uptake at 3 min post-injection (peak SUV=2.15 & 2.66), gradually reducing over the 45 minute scan (SUV =0.67 & 0.50). Toxicity studies in the mice showed no significant toxicity.
Conclusions: Our results demonstrate that [18F]F-ZW-cinacalcet binds to the CaSR and can radiographically identify parathyroid glands in rats and NHPs via PET imaging with excellent specificity over background tissue. This agent demonstrated rapid uptake and slow clearance from the parathyroids, while maintaining no toxicity. These findings support the feasibility of [18F]F-ZW-cinacalcet as a radiolabeling agent for parathyroid imaging in humans.