Esther Mena

11C-Acetate PET/CT in Localized Prostate Cancer: A Study with MRI and Histopathologic Correlation

This work characterizes the uptake of 11C-acetate in prostate cancer (PCa), benign prostate hyperplasia, and normal prostate tissue in comparison with multiparametric MRI, whole-mount histopathology, and clinical markers to evaluate the potential utility of 11C-acetate for delineating intraprostatic tumors in a population of patients with localized PCa. Methods: Thirty-nine men with presumed localized PCa underwent dynamic–static abdominal–pelvic 11C-acetate PET/CT for 30 min and 3-T multiparametric MRI before prostatectomy. PET/CT images were registered to MR images using pelvic bones for initial rotation–translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient-specific mold resulting in improved registration between the MRI, PET, and pathology. 11C-acetate PET standardized uptake values were compared with multiparametric MRI and pathology. Results: 11C-acetate uptake was rapid but reversible, peaking at 3–5 min after injection and reaching a relative plateau at approximately 10 min. The average maximum standardized uptake value (10–12 min) of tumors was significantly higher than that of normal prostate tissue (4.4 ± 2.05 [range, 1.8–9.2] vs. 2.1 ± 0.94 [range, 0.7–3.4], respectively; P < 0.001); however, it was not significantly different from that of benign prostatic hyperplasia (4.8 ± 2.01 [range, 1.8–8.8]). A sector-based comparison with histopathology, including all tumors greater than 0.5 cm, revealed a sensitivity and specificity of 61.6% and 80.0%, respectively, for 11C-acetate PET/CT and 82.3% and 95.1%, respectively, for MRI. The 11C-acetate accuracy was comparable to that of MRI when only tumors greater than 0.9 cm were considered. In a small cohort (n = 9), 11C-acetate uptake was independent of fatty acid synthase expression using immunohistochemistry. Conclusion: 11C-acetate PET/CT demonstrates higher uptake in tumor foci than in normal prostate tissue; however, 11C-acetate uptake in tumors is similar to that in benign prostate hyperplasia nodules. Although 11C-acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy when tissue damage after therapy may limit anatomic imaging methods.

Review of functional/anatomical imaging in oncology.

Patient management in oncology increasingly relies on imaging for diagnosis, response assessment, and follow-up. The clinical availability of combined functional/anatomical imaging modalities, which integrate the benefits of visualizing tumor biology with those of high-resolution structural imaging, revolutionized clinical management of oncologic patients. Conventional high-resolution anatomical imaging modalities such as computed tomography (CT) and MRI excel at providing details on lesion location, size, morphology, and structural changes to adjacent tissues; however, these modalities provide little insight into tumor physiology. With the increasing focus on molecularly targeted therapies, imaging radiolabeled compounds with PET and single-photon emission tomography (SPECT) is often carried out to provide insight into a tumor’s biological functions and its surrounding microenvironment. Despite their high sensitivity and specificity, PET and SPECT alone are substantially limited by low spatial resolution and inability to provide anatomical detail. Integrating SPECT or PET with a modality capable of providing these (i.e. CT or MR) maximizes their separate strengths and provides anatomical localization of physiological processes with detailed visualization of a tumor’s structure. The availability of multimodality (hybrid) imaging with PET/CT, SPECT/CT, and PET/MR improves our ability to characterize lesions and affect treatment decisions and patient management. We have just begun to exploit the truly synergistic capabilities of multimodality imaging. Continued advances in the development of instrumentation and imaging agents will improve our ability to noninvasively characterize disease processes. This review will discuss the evolution of hybrid imaging technology and provide examples of its current and potential future clinical uses.

Comparison of endorectal coil and nonendorectal coil T2W and diffusion-weighted MRI at 3 Tesla for localizing prostate cancer: correlation with whole-mount histopathology.

To compare utility of T2‐weighted (T2W) MRI and diffusion‐weighted MRI (DWI‐MRI) obtained with and without an endorectal coil at 3 Tesla (T) for localizing prostate cancer.

Localized Prostate Cancer Detection with 18F FACBC PET/CT: Comparison with MR Imaging and Histopathologic Analysis

PURPOSE To characterize uptake of 1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid ((18)F FACBC) in patients with localized prostate cancer, benign prostatic hyperplasia (BPH), and normal prostate tissue and to evaluate its potential utility in delineation of intraprostatic cancers in histopathologically confirmed localized prostate cancer in comparison with magnetic resonance (MR) imaging. MATERIALS AND METHODS Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study. Twenty-one men underwent dynamic and static abdominopelvic (18)F FACBC combined positron emission tomography (PET) and computed tomography (CT) and multiparametric (MP) 3-T endorectal MR imaging before robotic-assisted prostatectomy. PET/CT and MR images were coregistered by using pelvic bones as fiducial markers; this was followed by manual adjustments. Whole-mount histopathologic specimens were sliced with an MR-based patient-specific mold. (18)F FACBC PET standardized uptake values (SUVs) were compared with those at MR imaging and histopathologic analysis for lesion- and sector-based (20 sectors per patient) analysis. Positive and negative predictive values for each modality were estimated by using generalized estimating equations with logit link function and working independence correlation structure. RESULTS (18)F FACBC tumor uptake was rapid but reversible. It peaked 3.6 minutes after injection and reached a relative plateau at 15-20 minutes (SUVmax[15-20min]). Mean prostate tumor SUVmax(15-20min) was significantly higher than that of the normal prostate (4.5 ± 0.5 vs 2.7 ± 0.5) (P < .001); however, it was not significantly different from that of BPH (4.3 ± 0.6) (P = .27). Sector-based comparison with histopathologic analysis, including all tumors, revealed sensitivity and specificity of 67% and 66%, respectively, for (18)F FACBC PET/CT and 73% and 79%, respectively, for T2-weighted MR imaging. (18)F FACBC PET/CT and MP MR imaging were used to localize dominant tumors (sensitivity of 90% for both). Combined (18)F FACBC and MR imaging yielded positive predictive value of 82% for tumor localization, which was higher than that with either modality alone (P < .001). CONCLUSION (18)F FACBC PET/CT shows higher uptake in intraprostatic tumor foci than in normal prostate tissue; however, (18)F FACBC uptake in tumors is similar to that in BPH nodules. Thus, it is not specific for prostate cancer. Nevertheless, combined (18)F FACBC PET/CT and T2-weighted MR imaging enable more accurate localization of prostate cancer lesions than either modality alone.

DMSA study performed during febrile urinary tract infection: a predictor of patient outcome?

Technetium-99m dimercaptosuccinic acid (DMSA) study has been advocated as a method for the assessment of renal sequelae after acute febrile urinary tract infection (UTI). However, it is not known whether DMSA scintigraphy performed during acute UTI has any prognostic value for outcome assessment. The objective of this study was to evaluate the usefulness of DMSA scintigraphy performed during UTI as a predictor of patient outcome, to identify children at risk of events [vesico-ureteral reflux (VUR) or recurrent UTI] that may lead to the development of progressive renal damage. One hundred and fifty-two children (including 78 girls) with a mean age of 20 months (range 1 month to 12 years) with first febrile UTI were evaluated by DMSA scintigraphy during acute UTI. After acute UTI, children were explored by voiding cysto-urethrography. Children who presented an abnormal DMSA study, or a normal DMSA study but VUR or recurrent UTI, underwent a DMSA control study 6 months after UTI. Children with VUR were followed up by direct radionuclide cystography. DMSA scintigraphy performed during acute UTI was normal in 112 children (74%). In 95 of these children, follow-up DMSA scintigraphy was not performed owing to a good clinical outcome. In the remaining 17 children, follow-up scintigraphy was normal. Forty children (26%) presented abnormal DMSA study during acute UTI. Twenty-five of them presented a normal follow-up DMSA, and 15 presented cortical lesions. Children with abnormal DMSA had a higher frequency of VUR than children with normal DMSA (48% vs 12%). It is concluded that children with normal DMSA during acute UTI have a low risk of renal damage. Children with normal follow-up DMSA and low-grade VUR have more frequent spontaneous resolution of VUR.

Striatal D2 receptor binding as a marker of prognosis and outcome in untreated first-episode psychosis

In a preliminary 123I-IBZM SPECT study in first-episode psychosis, a relationship between striatal dopaminergic D2 receptor (D2R) binding and premorbid adjustment was suggested. These results were replicated in the present study (n = 18), and D2R binding at diagnosis predicted a high probability for schizophrenia outcome by 2-year follow-up. The present findings contribute to the evidence of abnormal D2R binding in schizophrenia and suggest that SPECT might be useful for outcome prediction in first-episode psychosis.

18F-Fluorodeoxyglucose Positron Emission Tomography in the Management of Patients with Thymic Epithelial Tumors

Purpose: There are limited data regarding the role of 18F-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET) imaging in management of patients with thymic epithelial tumors (TET). The primary objective of this study was to assess the usefulness of early [18F]-FDG PET to monitor treatment efficacy and its correlation with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with TETs. Experimental Design: [18F]-FDG PET/computed tomographic (CT) scans were conducted at baseline and after 6 weeks of treatment in patients enrolled in two phase II and one phase I/II clinical trials. On the basis of data from other solid tumors, metabolic response was defined as a reduction of [18F]-FDG uptake by more than 30% as assessed by average standardized uptake values (SUV) of up to five most metabolically active lesions. Results: Fifty-six patients with unresectable Masaoka stage III or IV TETs were included. There was a close correlation between early metabolic response and subsequent best response using RECIST (P < 0.0001–0.0003): sensitivity and specificity for prediction of best response were 95% and 100%, respectively. Metabolic responders had significantly longer progression-free survival (median, 11.5 vs. 4.6 months; P = 0.044) and a trend toward longer overall survival (median, 31.8 vs. 18.4 months; P = 0.14) than nonresponders. [18F]-FDG uptake was significantly higher in thymic carcinoma than in thymoma (P = 0.0004–0.0010). Conclusion: In patients with advanced TETs, early metabolic response closely correlates with outcome of therapy. [18F]-FDG PET may be used to monitor treatment efficacy and assess histologic differences in patients with advanced TETs. Clin Cancer Res; 19(6); 1487–93. ©2013 AACR.

Imaging Locally Advanced, Recurrent, and Metastatic Prostate Cancer: A Review

Importance Prostate cancer is the second leading cause of cancer deaths in US men. The course of prostate cancer is highly variable, and timely and accurate detection of clinically significant cancer is critical in positively affecting outcomes. Observations Molecular imaging methods and magnetic resonance imaging (MRI) are the most promising new developments for prostate tumor visualization. While the benefits of MRI are many, positron emission tomography (PET) radiotracers are still available only as research tools. Conclusions and Relevance The current research-based evidence on PET imaging has demonstrated encouraging potential in the initial diagnosis and detection of recurrence and metastases of prostate cancer.

Individual renal function based on 99mTc dimercaptosuccinic acid uptake corrected for renal size.

BackgroundDecreased relative 99mTc dimercaptosuccinic acid (99mTc-DMSA) uptake can be a consequence of abnormal kidney size, associated with normal or impaired function. When there is a small kidney, relative 99mTc-DMSA uptake is decreased, and it is sometimes difficult to distinguish a small, normal kidney from a hypofunctioning kidney. Here, relative renal function was studied by quantifying the relative 99mTc-DMSA uptake corrected for renal size (RCU). MethodsFive hundred and fifty-five consecutive patients (184 adults) aged 1 month to 82 years (mean, 14.8 years) underwent a 99mTc-DMSA study for various renal diseases. Results were compared with the relative 99mTc-DMSA uptake without size correction (RUU). Visual evaluation of images was also performed. ResultsIn 288 patients (52%) the relative 99mTc-DMSA uptake was normal, either uncorrected or corrected, for renal size; in 184 (33%) it was abnormal by both quantification methods; and in 83 (15%) it was abnormal only by one method. Two hundred and fifty-seven patients (46%) presented with decreased RUU in one kidney, associated with a small kidney in 73 patients (13%). RCU was normal in all of these 73 patients (100%, P<0.0001). The sensitivity and specificity of RCU for evaluating renal function in relation to small renal size and with respect to RUU were 72% and 97%, with positive and negative predictive values of 95% and 80%, and an accuracy of 85%. Visual analysis of the 73 studies with decreased RUU and normal RCU showed a small, normal kidney on 55 occasions (75%), cortical scars in eight (11%), and impaired bilateral function in 10 (14%). Visual analysis of 10 studies with normal RUU and decreased RCU showed dilated pyelocalyceal system in seven occasions (70%) and normal kidneys in three (P<0.0001). ConclusionIt is concluded that relative 99mTc-DMSA uptake corrected for renal size is a more accurate method for assessing individual renal function. When there is a small kidney, relative 99mTc-DMSA uptake corrected for renal size can distinguish between a normal and a hypofunctioning kidney.

A pilot study of the value of 18F-fluoro-deoxy-thymidine PET/CT in predicting viable lymphoma in residual 18F-FDG avid masses after completion of therapy.

Background Despite its success in diagnosing and staging lymphoma, 18F-FDG PET/CT can be falsely positive in areas of posttreatment inflammation. 3′-18F-fluoro-3′-deoxy-l-thymidine (18F-FLT) is a structural analog of the DNA constituent thymidine; its uptake correlates with cellular proliferation. This pilot study evaluates the ability of 18F-FLT PET/CT to distinguish viable lymphoma from posttreatment inflammatory changes in 18F-FDG avid residual masses. Methods Twenty-one patients with lymphoma with at least 1 18F-FDG avid residual mass after therapy underwent 18F-FLT PET/CT imaging. 18F-FDG and 18F-FLT uptake values were compared, including quantitative pharmacokinetic parameters extracted from the 18F-FLT time activity curves generated from dynamic data using graphical and nonlinear compartmental modeling. Results The true nature of the residual mass was confirmed by biopsy in 12 patients (8 positive and 4 negative for viable lymphoma and by follow-up CT and/or repeat 18F-FDG PET/CT imaging over 1 year); among the remaining 9 patients, 7 lesions resolved or decreased and 2 showed growth indicative of lymphoma. 18F-FLT PET SUVest.max was significantly higher in tumors than in benign lesions (5.5 [2.2] vs 1.7 [0.6]; P < 0.0001), whereas the difference in 18F-FDG SUVs was not significant (malignant, 7.8 [3.8] vs benign, 5.4 [2.4]; P = 0.11). All of the benign lesions had an 18F-FLT SUVest.max of less than 3.0. Conclusions 18F-FLT shows improved specificity over 18F-FDG in distinguishing residual lymphoma from posttreatment inflammation and may be useful in the evaluation of patients with residual 18F-FDG–positive masses after completing therapy.