Li Huo

Clinical translation of a dual integrin αvβ3 and GRPR targeting PET radiotracer 68Ga-NOTA-BBN-RGD

This study aimed to document the first-in-human application of a 68Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αvβ3 and gastrin-releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnostic value of 68Ga-BBN-RGD PET/CT in prostate cancer patients in comparison with 68Ga-BBN. Methods: Five healthy volunteers (4 men and 1 woman; age range, 28–53 y) were enrolled to validate the safety of 68Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software. Thirteen patients with prostate cancer (4 newly diagnosed and 9 posttherapy) were enrolled. All the patients underwent PET/CT scans 15–30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68Ga-BBN-RGD and also accepted 68Ga-BBN PET/CT within 2 wk for comparison. Results: With a mean injected dose of 107.3 ± 14.8 MBq per patient, no side effect was found during the whole procedure and 2 wk follow-up, demonstrating the safety of 68Ga-BBN-RGD. A patient would be exposed to a radiation dose of 2.90 mSv with an injected dose of 129.5 MBq (3.5 mCi), which is much lower than the dose limit set by the Food and Drug Administration. In 13 patients with prostate cancer diagnosed by biopsy, 68Ga-BBN-RGD PET/CT detected 3 of 4 primary tumors, 14 metastatic lymph nodes, and 20 bone lesions with an SUVmax of 4.46 ± 0.50, 6.26 ± 2.95, and 4.84 ± 1.57, respectively. Only 2 of 4 primary tumors, 5 lymph nodes, and 12 bone lesions were positive on 68Ga-BBN PET/CT, with the SUVmax of 2.98 ± 1.24, 4.17 ± 1.89, and 3.61 ± 1.85, respectively. Conclusion: This study indicates the safety and efficiency of a new type of dual integrin αvβ3– and GRPR-targeting PET radiotracer in prostate cancer diagnosis and staging.

Infection Imaging With 18F-FDS and First-in-Human Evaluation

PURPOSE The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported (18)F-FDS ((18)F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of (18)F-FDS and a first-in-human study were performed and discussed. METHODS A multifunctional synthesis module was employed for the radiosynthesis of (18)F-FDG ((18)F-2-fluorodeoxy glucose) and (18)F-FDS starting from (18)F ion using two-pot three-step fully automated reactions. The behavior of (18)F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers. RESULTS The uptake of (18)F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to (18)F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system. CONCLUSION We conclude that (18)F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted.

Unexpected primary osseous lymphoma as the cause of lactic acidosis in a patient suffering from pancreatitis.

A 45-year-old man was admitted due to acute pancreatitis. A severe lactic acidosis was found. Following active therapy, the signs and symptoms from pancreatitis was improved, but acidosis was exacerbated. FDG PET/CT images were acquired to investigate the etiology of lactic acidosis and/or other unknown pathology. The images showed widespread abnormal FDG activity in the bone marrows throughout the body, suggestive of hematologic malignancy, which was confirmed as primary osseous non-Hodgkin lymphoma following a histopathological examination of the bone marrow. Chemotherapy against lymphoma was initiated and status of the lactic acidosis was rapidly corrected.

Application of dual phase imaging of 11C-acetate positron emission tomography on differential diagnosis of small hepatic lesions.

Objective Previously we observed that dual phase 11C-acetate positron emission tomography (AC-PET) could be employed for differential diagnosis of liver malignancies. In this study, we prospectively evaluated the effect of dual phase AC-PET on differential diagnosis of primary hepatic lesions of 1–3 cm in size. Methods 33 patients having primary hepatic lesions with size of 1–3 cm in diameter undertook dual phase AC-PET scans. Procedure included an early upper-abdomen scan immediately after tracer injection and a conventional scan in 11–18 min. The standardized uptake value (SUV) was calculated for tumor (SUVT) and normal tissue (SUVB), from which 11C-acetate uptake ratio (as lesion against normal liver tissue, SUVT/SUVB) in early imaging (R1), conventional imaging (R2), and variance between R2 and R1 (ΔR) were derived. Diagnoses based on AC-PET data and histology were compared. Statistical analysis was performed with SPSS 19.0. Results 20 patients were found to have HCC and 13 patients had benign tumors. Using ΔR>0 as criterion for malignancy, the accuracy and specificity were significantly increased comparing with conventional method. The area under ROC curve (AUC) for R1, R2, and ΔR were 0.417, 0.683 and 0.831 respectively. Differential diagnosis between well-differentiated HCCs and benign lesions of FNHs and hemangiomas achieved 100% correct. Strong positive correlation was also found between R1 and R2 in HCC (r2 = 0.55, P<0.001). Conclusions Dual phase AC-PET scan is a useful procedure for differential diagnosis of well-differentiated hepatocellular carcinoma and benign lesions. The dynamic changes of 11C-acetate uptake in dual phase imaging provided key information for final diagnosis.

Intraductal Papillary Mucinous Neoplasm of the Pancreas With High Malignant Potential on FDG PET/MRI.

A 57-year-old man underwent FDG PET/CT to evaluate a mass in the head of the pancreas. The imaged revealed mildly, nonuniformly increased activity in the mass, but the exact location of the activity could not be determined on the low-dose noncontrast CT portion of the study. On subsequent PET/MRI images acquired 60 minutes after the FDG PET/CT study, the increased activity was clearly localized on the cystic wall. The pathological examination showed that the lesion was intraductal papillary mucinous neoplasm of the pancreas with high degree of dysplasia.

Kinetic Analysis of Dynamic 11 C-Acetate PET/CT Imaging as a Potential Method for Differentiation of Hepatocellular Carcinoma and Benign Liver Lesions

Objective: The kinetic analysis of 11C-acetate PET provides more information than routine one time-point static imaging. This study aims to investigate the potential of dynamic 11C-acetate hepatic PET imaging to improve the diagnosis of hepatocellular carcinoma (HCC) and benign liver lesions by using compartmental kinetic modeling and discriminant analysis. Methods: Twenty-two patients were enrolled in this study, 6 cases were with well-differentiated HCCs, 7 with poorly-differentiated HCCs and 9 with benign pathologies. Following the CT scan, all patients underwent 11C-acetate dynamic PET imaging. A three-compartment irreversible dual-input model was applied to the lesion time activity curves (TACs) to estimate the kinetic rate constants K1-k3, vascular fraction (VB) and the coefficient α representing the relative hepatic artery (HA) contribution to the hepatic blood supply on lesions and non-lesion liver tissue. The parameter Ki (=K1×k3/(k2 + k3)) was calculated to evaluate the local hepatic metabolic rate of acetate (LHMAct). The lesions were further classified by discriminant analysis with all the above parameters. Results: K1 and lesion to non-lesion standardized uptake value (SUV) ratio (T/L) were found to be the parameters best characterizing the differences among well-differentiated HCC, poorly-differentiated HCC and benign lesions in stepwise discriminant analysis. With discriminant functions consisting of these two parameters, the accuracy of lesion prediction was 87.5% for well-differentiated HCC, 50% for poorly-differentiated HCC and 66.7% for benign lesions. The classification was much better than that with SUV and T/L, where the corresponding classification accuracy of the three kinds of lesions was 57.1%, 33.3% and 44.4%. Conclusion: 11C-acetate kinetic parameter K1 could improve the identification of HCC from benign lesions in combination with T/L in discriminant analysis. The discriminant analysis using static and kinetic parameters appears to be a very helpful method for clinical liver masses diagnosis and staging.

Focal hepatic 11C-acetate activity on PET/CT scan due to lymphoid hyperplasia.

A 69-year-old woman complaining of abdominal bloating underwent ultrasonography, which revealed a small lesion in the left lobe of the liver. The lesion had elevated activity of both 18F-FDG and 11C-acetate on PET/CT scan and was suspected of being malignant. Postresection pathological examination demonstrated that this lesion was a focal intrahepatic lymphoid hyperplasia.

99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

Purpose The aim of this investigation was to determine the accuracy of the findings and the diagnoses of 99mTc-hydrazinonicotinyl-Tyr3-octreotide scan (99mTc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Methods Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before 99mTc-HYNIC-TOC imaging. 99mTc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Results Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. 99mTc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Conclusion 99mTc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

Hepatocelluar carcinoma in an accessory lobe of the liver revealed by 11C-acetate PET with a negative finding on FDG imaging.

An accessory lobe of the liver is a rare congenital anomaly, which is very difficult to diagnose preoperatively. Hepatocellular carcinoma in an accessory lobe of the liver is much rarer. We report here our findings of hepatocellular carcinoma in an accessory left lobe on C-acetate PET/CT images in a 67-year-old man who had both an unremarkable diagnostic contrast abdominal CT and a negative FDG PET/CT scan before the C-acetate PET/CT study.

11C-Acetate PET/CT Monitoring Therapy of Multiple Myeloma.

A 67-year-old man with newly diagnosed multiple myeloma underwent both FDG and C-acetate PET/CT sequentially on different days. There was increased FDG activity only in L1 vertebral body, but there was diffuse abnormal C-acetate activity throughout the skeletal system. After the successful therapy, the patient who was on remission clinically underwent follow-up PET/CT scans. Interestingly, L1 remained to have elevated FDG, although with less intensity. In contrast, there was no abnormal C-acetate activity anywhere in the body. The patient remained in remission clinically.