Erik Mittra

Stanford Medicine, Stanford, California, United States

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Publications (55)168.62 Total impact

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    ABSTRACT: The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF. We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality. Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed. The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.
    Clinical nuclear medicine. 01/2015; 40(1):1-8.
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    ABSTRACT: Sodium fluoride PET (F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered F-NaF and F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer F-NaF/F-FDG PET/CT with CT alone for detection of osseous metastasis.
    Clinical Nuclear Medicine 08/2014; · 2.86 Impact Factor
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    ABSTRACT: 4-dimensional computed tomography (4D-CT)-based pulmonary ventilation imaging is an emerging functional imaging modality. The purpose of this study was to investigate the physiological significance of 4D-CT ventilation imaging by comparison with pulmonary function test (PFT) measurements and single-photon emission CT (SPECT) ventilation images, which are the clinical references for global and regional lung function, respectively.
    International journal of radiation oncology, biology, physics 08/2014; · 4.59 Impact Factor
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    ABSTRACT: Purpose To present data from the first prospective pilot phase trial of breast cancer participants imaged with fluorine 18 ((18)F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2), a radiopharmaceutical agent used in positron emission tomographic (PET) imaging. Materials and Methods The local institutional review board approved the HIPAA-compliant protocol. Written informed consent was obtained from each patient. Eight women (age range, 44-67 years; mean age, 54.3 years ± 8.8 [standard deviation]) with newly diagnosed or recurrent breast cancer were recruited between November 2010 and February 2011. (18)F-FPPRGD2 PET/computed tomographic (CT) and (18)F-fluorodeoxyglucose (FDG) PET/CT examinations were performed within 3 weeks of each other. Dynamic (18)F-FPPRGD2 PET and two whole-body static (18)F-FPPRGD2 PET/CT scans were obtained. During this time, vital signs and electrocardiograms were recorded at regular intervals. Blood samples were obtained before the injection of (18)F-FPPRGD2 and at 24 hours and 1 week after injection to evaluate for toxicity. A nonparametric version of multivariate analysis of variance was used to assess the safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare the maximum standardized uptake values (SUVmax). Results (18)F-FPPRGD2 was well tolerated, without noticeable changes in vital signs, on electrocardiograms, or in laboratory values. A total of 30 lesions were evaluated at (18)F-FDG PET/CT and (18)F-FPPRGD2 PET/CT. The primary breast lesions had (18)F-FPPRGD2 uptake with SUVmax of 2.4-9.4 (mean, 5.6 ± 2.8) 60 minutes after injection, compared with (18)F-FDG uptake with SUVmax of 2.8-18.6 (mean, 10.4 ± 7.2). Metastatic lesions also showed (18)F-FPPRGD2 uptake, with SUVmax of 2.4-9.7 (mean, 5.0 ± 2.3) at 60 minutes, compared with (18)F-FDG uptake with SUVmax of 2.2-14.6 (mean, 6.6 ± 4.2). Conclusion Data from this pilot phase study suggest that (18)F-FPPRGD2 is a safe PET radiopharmaceutical agent. Evaluation of (18)F-FPPRGD2 in participants with breast cancer demonstrated significant uptake in the primary lesion and in the metastases. Larger cohorts are required to confirm these preliminary findings. © RSNA, 2014.
    Radiology 07/2014; · 6.21 Impact Factor
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    ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication in transplant patients. Although fluorine-18 2-fluoro-2-deoxyglucose PET and computed tomography (F-FDG PET/CT) has been used for the evaluation and management of patients with PTLD, its utility has yet to be documented. We were therefore prompted to review our experience with F-FDG PET/CT in PTLD. We retrospectively reviewed the records of consecutive patients who had undergone F-FDG PET/CT for evaluation of PTLD from January 2004 to June 2012 at our institution. F-FDG PET/CT scans were compared with other imaging modalities performed concurrently. A chart review of pertinent clinical information was also conducted. A total of 30 patients were identified (14 female and 16 male; 1.7-76.7 years of age, average: 23.8 years). Twenty-seven participants had biopsy-proven PTLD and another three had been treated for PTLD because of high clinical suspicion of disease and positive F-FDG PET/CT findings in the absence of histological diagnosis. Eighty-three percent of these PTLD patients had extranodal involvement. In 57% of the cases, F-FDG PET/CT detected occult lesions not identified on other imaging modalities or suggested PTLD in equivocal lesions. The more aggressive PTLD histological subtypes demonstrated higher SUVmax compared with the less aggressive subtypes. F-FDG PET/CT is beneficial in the diagnostic evaluation of patients with PTLD. F-FDG PET/CT has the ability to detect occult lesions not identified on other imaging modalities, particularly extranodal lesions. In addition, F-FDG PET/CT may predict the PTLD subtype, as the lesions with higher pathologic grade presented with significantly higher SUVmax compared with the less aggressive forms.
    Nuclear Medicine Communications 11/2013; · 1.37 Impact Factor
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    ABSTRACT: Preoperative lymphoscintigraphy (PLS) combined with intraoperative gamma probe (GP) localization is standard procedure for localizing the sentinel lymph nodes (SLN) in melanoma and breast cancer. In this study, we evaluated the ability of a novel intraoperative handheld gamma camera (IHGC) to image SLNs during surgery. The IHGC is a small-field-of-view camera optimized for real-time imaging of lymphatic drainage patterns. Unlike conventional cameras, the IHGC can acquire useful images in a few seconds in a free-running fashion and be moved manually around the patient to find a suitable view of the node. Thirty-nine melanoma and eleven breast cancer patients underwent a modified SLN biopsy protocol in which nodes localized with the GP were imaged with the IHGC. The IHGC was also used to localize additional nodes that could not be found with the GP. The removal of 104 radioactive SLNs was confirmed ex vivo by GP counting. In vivo, the relative node detection sensitivity was 88.5 (82.3, 94.6)% for the IHGC (used in conjunction with the GP) and 94.2 (89.7, 98.7)% for the GP alone, a difference not found to be statistically significant (McNemar test, p = 0.24). Small radioactive SLNs can be visualized intraoperatively using the IHGC with exposure time of 20 s or less, with no significant difference in node detection sensitivity compared to a GP. The IHGC is a useful complement to the GP, especially for SLNs that are difficult to locate with the GP alone.
    Physica Medica 11/2013; · 1.85 Impact Factor
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    ABSTRACT: Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R(2)=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone's mechanical strength and structural parameters, i.e., bulk Young's modulus (R(2)=0.67) and BV/TV (R(2)=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R(2)=0.92 for BV/TV and R(2)=0.71 for bulk Young's modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone's structural integrity.
    Acta Astronautica 11/2013; 92(1):79-88. · 0.82 Impact Factor
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    ABSTRACT: Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping. Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy. Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05). Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.
    Journal of Nuclear Medicine 10/2013; · 5.56 Impact Factor
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    ABSTRACT: Ficlatuzumab is a therapeutic agent targeting the hepatocyte growth factor (HGF)/c-MET pathway. We summarize preclinical work using this agent in a mouse brain orthotopic model of glioblastoma. Sequential experiments were done using 8- to 9-week old nude mice injected with 3x10^5 U87 MG (glioblastoma) cells into the brain. Evaluation of ficlatuzumab dose response for this brain tumor model and comparison of its response to ficlatuzumab and to temozolamide were performed. Subsequently, various small animal imaging modalities, including bioluminescence imaging (BLI), positron emission tomography (PET), and magnetic resonance imaging (MRI), were used with a U87 MG-Luc 2 stable cell line to evaluate the ability to non-invasively assess tumor growth and response to therapy. ANOVA was performed to evaluate for significant differences in the response. There was a survival benefit with ficlatuzumab alone or in combination with temozolamide. BLI was more sensitive than PET in detecting tumor cells. Fluoro-L-thymidine (FLT) PET provided a better signal-to-background ratio than fluorodeoxyglucose (FDG) PET. Additionally, both BLI and FLT PET showed significant changes over time in the control group as well as with response to therapy. MRI does not disclose any time-dependent change. Also, the MRI results showed a temporal delay in comparison to the BLI and FLT PET findings, showing similar results one drug cycle later. Targeting the (HGF)/c-MET pathway with the ficlatuzumab appears promising for the treatment of glioblastoma. Various clinically applicable imaging modalities including FLT, PET, and MRI provide reliable ways of assessing tumor growth and response to therapy.
    Clinical Cancer Research 08/2013; · 8.19 Impact Factor
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    ABSTRACT: Purpose Yttrium-90 (90Y) radioembolization dose planning requires balancing caution against toxicity with aggressiveness for efficacy, but each is impossible to predict based solely on morphologic imaging. We investigate the use of fusion MAA-sulfur colloid SPECT imaging to provide physiologic information relevant to dose calculation and outcomes. Materials and Methods A dual SPECT protocol was used with IA injection of technetium-99m (99mTc)-MAA (1 mCi) as a predictor of subsequent 90Y distribution, followed by IV 99mTc-sulfur colloid (5 mCi) as a biomarker for normal hepatic tissue. The SPECT data were co-registered and fused. A voxel based method was used to predict the 90Y radiation absorbed dose to functional hepatic tissue by calculation of 99mTc-MAA activity in voxels with 99mTc-sulfur colloid uptake. Similarly, the absorbed dose to tumor was predicted by calculation of 99mTc-MAA activity in voxels without 99mTc-sulfur colloid. Response (mRECIST) was recorded at 3 months, laboratory data were collected at 2, 4 and 8 weeks, and patients were followed until death. Retrospective SPECT based dosimetry was correlated with parameters of toxicity and efficacy and compared with standard parameters of dosimetry, administered activity, and whole liver absorbed dose. Results A total of 56 patients were included (32 M, 24 F; median age 62; 27 HCC, 29 CRC, 32 resin, 24 glass microspheres, median activity 2.02 GBq, median whole liver dose 70 Gray). Toxicity parameters (serum bilirubin, AST, ALT, albumin, hemoglobin, and platelets) correlated significantly with SPECT-based functional liver absorbed dose (median 38 Gy, p < 0.05). In addition, in uni- and multivariate analysis, SPECT-based tumor absorbed dose (median 117 Gy) showed strongest correlation with radiographic response (p < 0.05) and with overall survival (p < 0.05). Radiographic response correlated with survival, and responders survived longer than non-responders (median 16.9 vs 8.4 months; p < 0.01). Conclusion Fusion MAA-Sulfur colloid SPECT is useful to predict tumor and functional liver absorbed dose, which correlate with efficacy and toxicity, and may be used in the future to develop an individualized physiology-based dose-planning method.
    Journal of Vascular and Interventional Radiology 04/2013; 24(4):S34. · 2.15 Impact Factor
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    ABSTRACT: OBJECTIVE: The aim of this study was to compare Tc-MDP bone scanning, F NaF PET/CT, F FDG PET/CT, and whole-body MRI (WBMRI) for detection of known osseous metastases. PATIENTS AND METHODS: This prospective pilot trial (September 2007-April 2009) enrolled 10 participants (5 men, 5 women, 47-81 years old) diagnosed with cancer and known osseous metastases. F NaF PET/CT, F FDG PET/CT, and WBMRI were performed within 1 month for each participant. RESULTS: The image quality and evaluation of extent of disease were superior by F NaF PET/CT compared to Tc-MDP scintigraphy in all patients with skeletal lesions and compared to F FDG PET/CT in 3 of the patients with skeletal metastases. F NaF PET/CT showed osseous metastases where F FDG PET/CT was negative in another 3 participants. Extraskeletal metastases were identified by F FDG PET/CT in 6 participants. WBMRI with the combination of iterative decomposition of water and fat with echo asymmetry and least-squares estimation, short tau inversion recovery, and diffusion-weighted imaging pulse sequences showed fewer lesions than F NaF PET/CT in 5 patients, same number of lesions in 2 patients, and more lesions in 1 patient. WBMRI showed fewer lesions than F FDG in 3 patients and same lesions in 6 patients. CONCLUSIONS: Our pilot phase prospective trial demonstrated superior image quality and evaluation of skeletal disease extent with F NaF PET/CT compared to Tc-MDP scintigraphy and F FDG PET/CT, as well as the feasibility of multisequence WBMRI. In addition, F FDG PET/CT provided valuable soft-tissue information that can change disease management. Further evaluation of these findings using the recently introduced PET/MRI scanners is warranted.
    Clinical nuclear medicine 02/2013; · 3.92 Impact Factor
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    ABSTRACT: (18)F-FDG PET/CT is used in a variety of cancers, but because of variable rates of glucose metabolism, not all cancers are reliably identified. (18)F(-) PET/CT allows for the acquisition of highly sensitive and specific images of the skeleton. We prospectively evaluated combined (18)F(-)/(18)F-FDG as a single PET/CT examination for evaluation of cancer patients and compared it with separate (18)F(-) PET/CT and (18)F-FDG PET/CT scans. METHODS: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating (18)F(-) PET/CT, (18)F-FDG PET/CT, and combined (18)F(-)/(18)F-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. RESULTS: (18)F(-)/(18)F-FDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of (18)F-FDG PET/CT. In 19 participants, skeletal disease was more extensive on (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT than on (18)F-FDG PET/CT. In another 29 participants, (18)F(-) PET/CT and (18)F(-)/(18)F-FDG PET/CT showed osseous metastases where (18)F-FDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans. CONCLUSION: This trial demonstrated that combined (18)F(-)/(18)F-FDG PET/CT shows promising results when compared with separate (18)F(-) PET/CT and (18)F-FDG PET/CT for evaluation of cancer patients. This result opens the possibility for improved patient care and reduction in health-care costs, as will be further evaluated in future trials.
    Journal of Nuclear Medicine 12/2012; · 5.56 Impact Factor
  • Erik Supratik Mittra
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    ABSTRACT: LEARNING OBJECTIVES 1) To identify the advantages of F-18 NaF PET/CT imaging in oncology. 2) To understand the importance of a standardized imaging protocol. 3) To become comfortable differentiating benign from malignant lesions on F-18 NaF PET/CT. ABSTRACT F-18 NaF PET/CT has been shown to have higher sensitivity and specificity than planar 99m-Tc MDP bone scanning in several small studies. The concomitant acquisition of anatomic images permits immediate correlation of any abnormal findings. Additionally, F-18 NaF PET/CT bone imaging can be quantitated, allowing bone disease to be “measureable”, increasing its utility therapy monitoring. When a consistent F-18 NaF uptake period is used, the SUV values are highly reproducible, and due to the high extraction fraction, high quality images can be obtained with a radiation dose exposure similar to that of Tc-99m MDP (including the low dose CT scan). This presentation will discuss the benefits and challenges of F-18 NaF PET/CT in oncology.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
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    ABSTRACT: (4S)-4-(3-[(18)F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [(18)F]FSPG) is a new tracer to image x(C)(-) transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [(18)F]FSPG in patients relative to 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG). The correlation of [(18)F]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed. Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [(18)F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [(18)F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. [(18)F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [(18)F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [(18)F]FSPG detected 59 of 67 (88%) [(18)F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [(18)F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [(18)F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [(18)F]FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01). [(18)F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [(18)F]FSPG PET may assess x(C)(-) transporter activity in patients with cancer. Clin Cancer Res; 18(19); 5427-37. ©2012 AACR.
    Clinical Cancer Research 08/2012; 18(19):5427-37. · 8.19 Impact Factor
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    ABSTRACT: The difficulty in delineating brain tumor margins is a major obstacle in the path toward better outcomes for patients with brain tumors. Current imaging methods are often limited by inadequate sensitivity, specificity and spatial resolution. Here we show that a unique triple-modality magnetic resonance imaging-photoacoustic imaging-Raman imaging nanoparticle (termed here MPR nanoparticle) can accurately help delineate the margins of brain tumors in living mice both preoperatively and intraoperatively. The MPRs were detected by all three modalities with at least a picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to MPR accumulation and retention by the tumors, with no MPR accumulation in the surrounding healthy tissue, allowing for a noninvasive tumor delineation using all three modalities through the intact skull. Raman imaging allowed for guidance of intraoperative tumor resection, and a histological correlation validated that Raman imaging was accurately delineating the brain tumor margins. This new triple-modality-nanoparticle approach has promise for enabling more accurate brain tumor imaging and resection.
    Nature medicine 04/2012; 18(5):829-34. · 28.05 Impact Factor
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    ABSTRACT: PURPOSE 99mTc-MDP has been the standard method for bone scintigraphy (BS) for more than 3 decades. The role of FDG PET/CT is proven in a variety of cancers for which it has changed the practice of oncology. There are few prospective studies comparing these 2 methods of detection of skeletal metastases in sarcoma patients. The purpose of this study was to compare FDG PET/CT and 99mTc-MDP BS in the detection of primary and/or metastatic osseous lesions. METHOD AND MATERIALS 48 consecutive patients with histopathological confirmation of Ewing’s sarcoma (EWS, n = 24) or other childhood sarcomas (rhabdomyosarcoma (n = 14), osteosarcoma (n = 5), synovial sarcoma (n = 3), spindle cell sarcoma (n = 1), high grade undifferentiated sarcoma (n = 1)) who had FDG PET/CT and 99mTc-MDP BS performed at our institution between 2003-2010 were included in this retrospective analysis. Only those patients who had these studies done within 1 month of each other were included. There were 24 males and 24 females, with an average age at time of diagnosis of 15.18 ± 8.1 years. Sensitivities and specificities were calculated for detection of osseous malignant lesions. RESULTS No differences in sensitivity or specificity between the PET/CT and BS were observed in these cohorts, except for detection of bone metastases from non-EWS where PET performed better than BS. PET/CT also detected disease outside the skeleton in 29.2% of EWS patients and 62.5% of non-EWS patients. In EWS, BS was 85.7% sensitive and 94.4% specific for detection of the primary lesions (n=22), while PET was 85.7% sensitive and 88.9% specific. For detection of osseous metastases (n=24), BS was 60% sensitive and 93.1% specific, while PET was 66.7% sensitive and 96.4% specific. In non-EWS, BS was 78.6% sensitive and 100% specific for detection of the primary osseous lesions (n=11), while PET was 76.9% sensitive and 100% specific. For detection of osseous metastases (n=25), BS was 33.3% sensitive and 97.4% specific, while PET was 66.7% sensitive and 100% specific. CONCLUSION While this is a small cohort and the results need to be confirmed in larger studies, it appears that FDG PET/CT may successfully provide similar information regarding skeletal lesions as BS in patients with sarcomas. In addition, FDG PET/CT detected disease outside of the skeleton in a significant number of EWS and non-EWS. CLINICAL RELEVANCE/APPLICATION FDG PET/CT provides similar information regarding skeletal lesions as BS.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 12/2011
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    ABSTRACT: PURPOSE Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication after both solid organ and bone marrow transplant. PTLD patients are typically staged with the same protocols as for malignant lymphomas. These protocols have incorporated FDG PET/CT over the past several years after showing clear clinical benefit in lymphomas. While a few reports have suggested added benefits of PET/CT in the diagnosis and therapeutic approach to PTLD, its utility has not been proven. Therefore, we were prompted to review our experience with FDG PET/CT in PTLD. METHOD AND MATERIALS A retrospective search of our institution's PET database for all patients diagnosed with PTLD who had undergone PET/CT imaging from 10/2006 to 3/2011 was performed with local IRB approval. A total of 21 patients (11 women, 10 men; mean age, 18.2 years; range 2-64 years) were identified to have biopsy-proven PTLD. The PET/CT findings were compared to other imaging modalities performed at the time of initial diagnosis, including contrast enhanced CT (ceCT) and MRI. A chart review of pertinent information, including biopsy results and clinical outcome, was also performed. RESULTS All FDG PET/CT scans were performed for initial staging purposes. A total of 18 patients (86%) had extranodal involvement at the time of their baseline studies, most commonly involving small bowel (8), bone (6), lung (6), spleen (5) and liver (4). The SUVmax for extra-nodal disease ranged 1.8-42 (mean 11.4), while the SUVmax ranged 2.2 - 44.8 (mean 12.1) for nodal sites of involvement. In addition, in 13 of the 21 patients (62%), FDG PET/CT either detected occult lesions not seen on other imaging modalities or suggested malignancy in previously presumed stable lesions. CONCLUSION FDG PET/CT is useful in staging and evaluating both nodal and extranodal sites of involvement in patients with PTLD. This retrospective study demonstrates intense FDG uptake at both nodal and extra-nodal sites of disease. FDG PET/CT appears useful in detecting occult lesions not visualized on other corresponding imaging modalities, particularly for extra-nodal sites of involvement. CLINICAL RELEVANCE/APPLICATION This study provides further evidence that FDG PET/CT could be beneficial for the staging of patients diagnosed with PTLD.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: PURPOSE FDG PET/CT is well established in clinical practice for the initial cancer staging and the subsequent monitoring of response to therapy. Sodium fluorine-18 (NaF) can be used as a skeletal tracer in current PET/CT scanners. The combined administration of NaF and FDG in a single PET/CT scan may improve patient convenience, while reducing healthcare costs. However, this novel imaging method has not been compared to CT alone for the detection of skeletal metastases. METHOD AND MATERIALS This is a retrospective review of 43 patients (32 men and 11 women, 19-84 year-old) with proven malignancy, who had separate NaF PET/CT, FDG PET/CT and combined NaF/FDG PET/CT scans (total of 3 scans per patient). The 3 PET/CT scans were sequentially performed within a 2 weeks interval for each patient. A direct comparison for each detected skeletal metastasis was performed among the 3 scans and CT alone. RESULTS 21 exams identified osseous metastases on at least 1 of the 4 (NaF PET, FDG PET, NaF/FDG PET and CT) imaging modalities (49% of total exams). The combined NaF/FDG PET compared favorably with individual NaF PET and FDG PET, as all 17 exams positive for osseous metastasis on either NaF or FDG PET were also positive on the combined NaF/FDG scan. In contrast, when CT was interpreted in the absence of PET correlation, 6 exams (35%) were incorrectly considered negative, with 4 of these 6 false negatives detected only on NaF PET and combined NaF/FDG PET. Of these 6 ‘PET-positive/CT-negative’ exams, CT abnormalities were in fact noted by the reviewers in 5 cases, but were interpreted as either benign or likely benign. Finally, 7 of 11 exams in which CT detected lesions not seen on FDG PET were subsequently scored positive for metastatic disease by NaF PET and combined NaF/FDG PET. CONCLUSION The combined NaF/FDG PET/CT detects more osseous metastases than CT alone, without loss of sensitivity in comparison to separate FDG PET or NaF PET. The simultaneous use of NaF and FDG PET contributed greatly to the degree of concordance between scintigraphy and radiography. These findings provide a clinically relevant rationale for the use of combined NaF/FDG PET/CT in the management of oncologic patients and should be further evaluated in larger cohorts. CLINICAL RELEVANCE/APPLICATION The simultaneous use of NaF and FDG PET contributes greatly to the degree of concordance between scintigraphy and radiography.
    Radiological Society of North America 2011 Scientific Assembly and Annual Meeting; 11/2011
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    ABSTRACT: Typically, (18)F-FDG PET/CT and (18)F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined (18)F-FDG/(18)F-NaF PET/CT scan with that of a separate (18)F-FDG-only PET/CT scan. There were 62 patients enrolled in this prospective trial. All had both an (18)F-FDG-alone PET/CT scan and a combined (18)F-FDG/(18)F-NaF PET/CT scan. Of the 62 patients, 53 (85%) received simultaneous tracer injections, while 9 (15%) received (18)F-NaF subsequent to the initial (18)F-FDG dose (average delay 2.2 h). Images were independently reviewed for PET findings by two Board-Certified nuclear medicine physicians, with discrepancies resolved by a third reader. Interpreters were instructed to only report findings that were concerning for malignancy. Reading the (18)F-FDG-only scan first for half of the patients controlled for order bias. In 15 of the 62 patients (24%) neither the (18)F-FDG-only PET/CT scan nor the combined (18)F-FDG/(18)F-NaF PET/CT scan identified malignancy. In the remaining 47 patients who had PET findings of malignancy, a greater number of lesions were detected in 16 of 47 patients (34%) using the combined (18)F-FDG/(18)F-NaF PET/CT scan compared to the (18)F-FDG-only PET/CT scan. In 2 of these 47 patients (4%), the (18)F-FDG-only scan demonstrated soft tissue lesions that were not prospectively identified on the combined study. In 29 of these 47 patients (62%), the combined scan detected an equal number of lesions compared to the (18)F-FDG-only scan. Overall, 60 of all the 62 patients (97%) showed an equal or greater number of lesions on the combined scan than on the (18)F-FDG-only scan. The current study demonstrated that (18)F-FDG and (18)F-NaF can be combined in a single PET/CT scan by administering the two radiopharmaceuticals simultaneously or in sequence on the same day. In addition to patient convenience and reduced radiation exposure from the CT component, the combined (18)F-FDG/(18)F-NaF PET/CT scan appeared to increase the sensitivity for detection of osseous lesions compared to the (18)F-FDG-only PET/CT scan in the studied population.
    European Journal of Nuclear Medicine 11/2011; 39(2):262-70. · 4.53 Impact Factor
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    ABSTRACT: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets α(v)β(3) integrin, in the first volunteers imaged with this tracer. The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/mmol ± 714 [44.4 GBq/mmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests. The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of (18)F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096). (18)F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.
    Radiology 07/2011; 260(1):182-91. · 6.21 Impact Factor

Publication Stats

607 Citations
168.62 Total Impact Points

Institutions

  • 2008–2014
    • Stanford Medicine
      • • Stanford Emergency Department (Hospitals and Clinics)
      • • Department of Radiology
      Stanford, California, United States
  • 2013
    • Lucile Packard Children’s Hospital at Stanford
      Palo Alto, California, United States
  • 2007–2012
    • Stanford University
      • Department of Radiology
      Stanford, CA, United States
    • VA Palo Alto Health Care System
      Palo Alto, California, United States
  • 2002–2006
    • Stony Brook University
      • Department of Biomedical Engineering
      Stony Brook, NY, United States
    • State University of New York
      New York City, New York, United States