Sun Young Chae

Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-l-Glutamate PET of Inflammatory and Infectious Lesions

We explored system xC− transporter activity and the detection of inflammatory or infectious lesions using (4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG) PET. Methods: In 10 patients with various inflammatory or infectious diseases, as many as 5 of the largest lesions were selected as reference lesions. 18F-FSPG images were assessed visually and quantitatively. Expression levels of xCT, CD44, and surface markers of inflammatory cells were evaluated by immunohistochemistry. Results: 18F-FSPG PET detected all reference lesions. 18F-FSPG uptake in sarcoidosis was significantly higher than that in nonsarcoidosis. The lesion–to–blood-pool SUV ratio for 18F-FSPG was comparable to that for 18F-FDG in sarcoidosis. In nonsarcoidosis, however, it was significantly lower. In 5 patients with available tissue samples, the SUVmax for 18F-FSPG and CD163 were negatively correlated (ρ = –0.872, P = 0.054). Conclusion: 18F-FSPG PET may detect inflammatory lesions when activated macrophages or monocytes are present, such as in sarcoidosis.

A randomized feasibility study of 18F-fluoroestradiol positron emission tomography to predict pathological response to neoadjuvant systemic therapy in estrogen receptor-rich postmenopausal breast cancer

The aim of this study was to explore the ability of 18F-fluoroestradiol (18F-FES) PET/CT imaging to predict pathologic response to neoadjuvant therapy in postmenopausal women with estrogen receptor (ER)–rich breast cancer. Methods: This was a prospective, single-center study conducted as a substudy of the neoadjuvant study of chemotherapy versus endocrine therapy in postmenopausal patients with primary breast cancer (NEOCENT) trial. Patients with ER-rich breast cancer were randomized to neoadjuvant chemotherapy (NC) or neoadjuvant endocrine therapy (NET). The baseline SUVmax of 18F-FES PET/CT was measured. The pathologic response was assessed by the Miller–Payne system as nonresponse (grades 1 and 2) and response (grades 3–5). Results: Twenty-six patients were enrolled, with pathologic response achieved in 25 (NC, 12; NET, 13). Two patients achieved pathologic complete response after NC, but the remaining 23 patients had residual disease after NC or NET. Eight of 12 patients responded to NC, and 4 of 13 to NET; the difference was marginally significant (P = 0.07). In the NC group, the 2 patients with 18F-FES–negative tumors and none of the 10 patients with 18F-FES–avid tumors achieved pathologic complete response (P = 0.02). No difference in the SUVmax between responders and nonresponders was observed in either group. However, 5 of 7 NC patients with a baseline SUVmax of less than 7.3 achieved pathologic response, whereas none of the 5 NET patients with an SUVmax of less than 7.3 were responders (P = 0.03). The SUVmax values of the NC group were negatively correlated with percentage reduction of tumor cellularity (r = −0.63, P = 0.03), whereas those of the NET group showed positive correlation (r = 0.62, P = 0.02). During the median follow-up of 74 mo (range, 44–85 mo), recurrence occurred in only 4 NET patients. In patients with an SUVmax of less than 7.3, recurrence occurred in none of the 8 NC patients and 2 of the 5 NET patients (P = 0.13). Conclusion: Postmenopausal women who are ER-positive, but 18F-FES–negative, may benefit from NC rather than NET. 18F-FES PET/CT has the potential to predict response to neoadjuvant therapy in postmenopausal women with ER-rich breast cancer.

Evaluation of selective positron emission tomography template method for spatial normalization of amyloid imaging with 11C-Pittsburgh Compound B.

Objective Spatial normalization of 11C-Pittsburgh Compound B (PiB) images is challenging for an automatic quantitative analysis without magnetic resonance imaging (MRI) because of different distribution patterns between amyloid positive and negative images. To overcome this issue, we evaluated a selective positron emission tomography template (SPT) method. Materials and Methods Three sets of single positron emission tomography templates were created: PiB negative template, PiB positive template, and mixed template. Sixty-one patients with dementia were enrolled as the validation cohort. Magnetic resonance imaging–aided normalization method was used as a reference. The SPT method was based on visual classification (positive, negative, and equivocal). The optimal templates for each visual group were determined by correlation values and average percent errors (APEs) with MRI-aided normalization. The results of the SPT and the single template methods were compared with those of MRI-aided normalization in terms of correlation values, APEs, and concordance rates. Results The SPT (PiB negative template for the negative and equivocal groups and PiB positive template for the positive group) showed higher correlations and concordance rate and lower APEs with MRI-aided normalization than did the single template. Conclusions Use of the SPT provides accurate normalization of amyloid images without MRI.

Glycoprotein IIb/IIIa receptor imaging with18F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study

18F-GP1 is a derivative of elarofiban with a high affinity to activated platelet glycoprotein IIb/IIIa and favorable in vivo characteristics for thrombus imaging in preclinical models. We aimed to explore the detection rate of thromboembolic foci with 18F-GP1 PET/CT in patients with acute venous thromboembolism and to evaluate the safety, biodistribution, pharmacokinetics, and metabolism of 18F-GP1. Methods: We studied patients who had signs or symptoms of acute deep-vein thrombosis (DVT) of the leg or acute pulmonary embolism (PE) within 14 d before 18F-GP1 PET/CT and had thromboembolic foci confirmed by conventional imaging (n = 10 for DVT and n = 10 for PE). Dynamic whole-body PET/CT images were acquired for up to 140 min after injection of 250 MBq of 18F-GP1. Results: 18F-GP1 PET/CT was well tolerated, without any drug-related adverse events, and showed high initial uptake in the spleen, kidneys, and blood pool, followed by rapid clearance. The overall image quality was excellent and allowed interpretation in all patients. 18F-GP1 PET/CT identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel-level analysis revealed that 18F-GP1 PET/CT detected 89% (68/76) of vessels with DVT and 60% (146/245) with PE. Importantly, 18F-GP1 PET/CT showed increased uptake in 32 vessels that were not detected by conventional imaging, of which 25 were located in distal veins of the lower extremity in 12 patients. A positive correlation was found between 18F-GP1 uptake and P-selectin–positive circulating platelets (r = 0.656, P = 0.002). Conclusion: 18F-GP1 is a promising PET tracer for imaging acute venous thromboembolism in patients. 18F-GP1 PET/CT may identify thrombi in distal veins of the leg, where conventional imaging has limitations.

Predictors of Renal Functional Improvement After Pyeloplasty in Ureteropelvic Junction Obstruction: Clinical Value of Visually Assessed Renal Tissue Tracer Transit in 99mTc-mercaptoacetyltriglycine Renography

OBJECTIVE To determine the clinical value of visually assessed renal tissue transit time (TTT) in 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography for patients undergoing pyeloplasty. MATERIALS AND METHODS Medical records of 164 patients who underwent dismembered pyeloplasty were retrospectively reviewed. Baseline and postoperative renal ultrasonography and 99mTc-MAG3 renography were performed. Two urologists blinded to clinical data evaluated the renography and classified TTT as timely or delayed based on visualization of the tracer in the kidney pelvis between 2 and 10 minutes. Renal functional change after pyeloplasty was compared between patients in the timely and delayed groups. RESULTS A total of 126 patients (median age, 9 months) were evaluated after excluding patients with bilateral ureteropelvic junction obstruction, a single functioning kidney, duplicated ureter, or <3 months of follow-up. There were no differences between 89 patients with timely TTT and 37 patients with delayed TTT in mean preoperative hydronephrosis grade (3.7 vs 3.8) and pelvic diameter (3.1 cm vs 3.4 cm). Although the pre- and postoperative mean values of differential renal function (DRF) were significantly higher in the timely group than in the delayed group (47.2% vs 38.3% and 47.9% vs 44.6%), DRF change was greater in the delayed group (6.3% vs 0.6%). In multivariate analysis, delayed TTT was the only significant predictor of >5% improvement in renal function after pyeloplasty. CONCLUSION Delayed TTT in 99mTc-MAG3 renography was a significant predictor of renal functional improvement after pyeloplasty in ureteropelvic junction obstruction. Because substantial improvement of renal function is anticipated, we recommend immediate pyeloplasty in patients with delayed TTT and decreased DRF.