Abstract
241033
Introduction: 11C-MePro is a novel amino acid PET radiotracer developed for tumors, especially for pancreatic cancer detection. 11C-MePro utilizes a certain amino acid transporter (transporter X, unpublished data) that is overexpressed in neoplasms, particularly in pancreatic ductal carcinoma. The aim of this study was to evaluate the biodistribution and radiation dosimetry from 11C-MePro PET imaging in healthy males as a first-in-human study. In addition, the expression of transporter X and glucose transporter 1 (GLUT-1), which is a transporter of 18F-FDG, was exploratively analyzed using pancreatic precancerous lesions and early stages of pancreatic cancer specimens obtained by surgery.
Methods: This study was approved by certificated review board as a clinical trial(L21-011) and study on Ethical Guidelines (N22-021). 11C-MePro was synthesized in our laboratory with high specific activity. Six healthy Japanese males (mean age: 33±11; age range 20−49) were intravenously injected with 11C-MePro (mean: 338±12MBq; range 327−353 MBq). A dynamic PET scan of the heart and upper abdomen was performed at 0−4 min, followed by 17 times whole-body static PET scans were performed at 5−90 min using PET/CT camera. After reconstructing PET image data, PMOD software was used to determine VOIs in each organ. A time-activity curve was derived from the VOIs to estimate the biodistribution and radiation dosimetry. IDAC-Dose 2.1 software was used to determine effective doses for the whole body. Immunohistochemical (IHC) staining for transporter X and GLUT-1 were performed on postoperative specimens to exploratorily evaluate protein expression in pancreatic lesions. The IHC staining sites to be evaluated were determined from the hematoxylin and eosin-stained images of the postoperative pancreatic specimens.
Results: There were no significant changes in vital signs and laboratory data including blood count, liver function, and renal function after injection of 11C-MePro. For PET imaging, the uptake of blood (heart contents) reached the SUVmean of 30.9±12.0 and decreased bi-exponentially. The accumulation of radiotracer in kidneys reached a peak at SUVmean; 16.7±3.1 at 20 min and consistently plateaued during the observation period up to 90 min. In contrast, pancreas was a relatively lower uptake organ: SUVmean 2.37±0.22 at 20 min and 2.44±0.15 at 40 min. Lungs, brain, muscle, and other soft tissue were also lower uptake organs. The uptake of liver was SUVmean 4.04±0.43 at 20 min and 4.53±0.32 at 40 min. In the dosimetry analysis, the higher absorbed doses were estimated for kidneys with a mean absorbed dose of 23.8±4.50 μGy/MBq. Radiation absorbed doses were relatively mild in lungs (6.44±0.80 μGy/MBq), pancreas (7.03±0.99 μGy/MBq), liver (9.07±1.38 μGy/MBq), respectively. The average effective total-body dose was calculated to be 4.45±0.19 μSv/MBq, estimated as 0.82−1.65 mSv from the administration of 185−370 MBq of 11C-MePro as an adult human.
Transporter protein expression analysis in postoperative pancreatic specimens showed positive for transporter X but negative or weakly positive for GLUT-1 in both pancreatic precancerous lesions and early stages of pancreatic cancer. This suggests that 11C-MePro PET/CT may be able to detect early stages of pancreatic abnormality that are undetectable by 18F-FDG PET/CT.
Conclusions: The biodistribution and radiation dosimetry of 11C-MePro were confirmed in this first-in-human study. 11C-MePro provides an excellent whole-body PET image with a reasonable radiation dose in normal volunteers. Furthermore, evaluation of pancreatic molecular pathology showed that 11C-MePro is a promising PET radiotracer for the detection of pancreatic cancer.
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