| Objective:This study aims at investigating the pharmacokinetic pattern and radiation dosimetry of68Ga-NOTA-PRGD2in healthy volunteers and to evaluate this novel PET/CT-based integrin receptor imaging technique in diagnosis of lung cancer.Method:This clinical trial was approved by the ethics committee of Chinese Academy of Medical Sciences and Peking Union Medical College Hospital.Seven healthy volunteers (M3, F4,38-65y) and18patients (M12, F6,40-82y) were enrolled. They all signed informed consents. Ga-NOTA-PRGD2was on-site produced with the radiochemical purity all exceeded97%. A Siemens Biograph128TrueV TrueX mCT was used for scanning. After the whole-body low-dose CT scanning, the tracer was injected intravenously, then serial PET acquisitions were performed in a whole-body dynamic mode from pelvic bottom to skull base. The scans consisted of19～23passes and each pass contained5-7bed-positions. The duration for each bed-position was3sec for the1-8passes,6sec for the9-14passes,60sec for the15-17passes,120sec for the next passes except for the last pass which lasted240sec. The whole scanning lasted from60min to2h. For the healthy volunteers, blood pressure, pulse, breathe rate, and temperature were measured and liver and renal functions as well as routine blood and urine tests were examined right before and24h after the scans. All patients accepted routine18F-FDG PET/CT within a week for comparison. All suspect lung lesions were surgical removed and analyzed histologically. The MI applications in the Siemens MMWP workstation were used for post-processing. The volume of interest (VOI) of the lesions and15kinds of organs or tissues were drawn by the same physician. The volumes (cm3) and radioactivivity (Bq/ml) were recorded. The O LINDA1.0software (Organ Level Internal Dose Assessment/Exponential Modeling computer software, Vanderbilt University,2003) was used for radiation dosimetry calculation. The same method was used to measure the volume and radioactivivity of suspicious lesions. The results were translated into SUV form for adioact and comparision. Immunohistochemical staining of CD31, CD34, Ki67and avβ3integrin were performedusing the pathological samples.Results:No side effect was found related to the68Ga-NOTA-PRGD2PET/CT scan. 68Ga-NOTA-PRGD2was rapidly cleared from the blood pool and primarily excreted though urinary system. The highest adioactivity was found in urinay system, including the kidneys, ureters and bladder. The spleen, liver, choroid plexus, uterus, intestines, and thyroid showed moderate uptake. The radiation dosimetry was equivalent to these of the reported similar agents.The curve of radioactivity over time showed that the agent was relatively stable in the organs and lesions after15minutes. Blood-pool activity was declined over time. The lungs’ uptake was low, which merits high target to background ratio of the lung malignancies. The malignant lesions, including the primary foci and lymphatic and bone metastases, became prominent15minutes after intravenous injection of68Ga-NOTA-PRGD2. The SUVs were1.94±0.64at15mins,1.99±0.76at30mins and2.02±0.98at60mins, which were significantly higher than those of the benign lesions (SUV=0.95±0.85at15mins, P=0.0098and SUV=0.98±0.86at30mins, P=0.0233), except for the60mins time point. If at15min SUV>1.25was considered as positive, the lesion-based sensitivity, specificity and accuracy of68Ga-NOTA-PRGD2PET/CT scan were88.9%(16/18),80%(4/5) and87.0%(20/23), respectively. If at30min S UV>1.25was considered as positive, the lesion-based sensitivity, specificity and accuracy of68Ga-NOTA-PRGD2PET/CT scan were82.4%(14/17),80%(4/5) and85.6%(18/22), respectively. There was a significant difference of SUV between adenocarcinoma and squamous cell carcinoma of lung.Conclusion: This translational study preliminarily indicated the safety of68Ga-NOTA-PRGD2PET/CT and the efficacy of the method in diagnosis of lung cancer. |
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