A Weight Index for the Standardized Uptake Value in 2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose-Positron Emission Tomography

Introduction Known errors in the standardized uptake value (SUV) caused by variations in subject weights W encountered can be corrected by lean body mass or body surface area (bsa) algorithms replacing W in calculations. However this is infrequently done. The aims of the work here are: quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (cv) for a population can be expected. Methods Selected for analyses were 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed tomography (CT) scans at the University of Tennessee as well as from the literature. A weight sensitivity index was defined as −n=slope of ln(SUV/W) vs. lnW. The portion of the SUV variability due to this trend is removed by using the defined SUV}}_{n} = {Q \times W^{n} \times W_{{{\text{avg}}}} ^{{1 - n}} } \mathord{\left/ {\vphantom {{Q \times W^{n} \times W_{{{\text{avg}}}} ^{{1 - n}} } {{\text{ID}}}}} \right. \kern-\nulldelimiterspace} {{\text{ID}}}$$" align="middle" border="0">, or a virtually equal SUV _m using SUV}}_{m} = Q \times {{\left( {wW + {\left( {1 - w} \right)}W_{{{\text{avg}}}} } \right)}} \mathord{\left/ {\vphantom {{{\left( {wW + {\left( {1 - w} \right)}W_{{{\text{avg}}}} } \right)}} {{\text{ID}}}}} \right. \kern-\nulldelimiterspace} {{\text{ID}}}$$" align="middle" border="0">, with Q and ID being tissue specific-activity and injected dose. SUV}}_{n} \,or\,{\text{of}}\,{\text{SUV}}_{m} } \right)}} \mathord{\left/ {\vphantom {{{\left( {{\text{cv}}\,{\text{of}}\,{\text{SUV}}_{n} \,or\,{\text{of}}\,{\text{SUV}}_{m} } \right)}} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{traditional}}\,{\text{SUV}}} \right)}}}} \right. \kern-\nulldelimiterspace} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{traditional}}\,{\text{SUV}}} \right)}}$$" align="middle" border="0"> measures performance. Adapting to animal studies’ tradition, SUV}}_{m}$$" align="middle" border="0"> is preferred over the conventional . Results For FDG in adults from averaging over most tissues. In children, however, . Tissues have the same index if their influx constants are independent of W. Suggested, therefore, is a very simplified SUV}}_{m} = Q \times \frac{1}{2}{{\left( {W + W_{{{\text{avg}}}} } \right)}} \mathord{\left/ {\vphantom {{{\left( {W + W_{{{\text{avg}}}} } \right)}} {{\text{ID}}}}} \right. \kern-\nulldelimiterspace} {{\text{ID}}}$$" align="middle" border="0">, which is dimensionless and keeps the same population averages as traditional SUVs. It achieves SUV}}} \right)}^{2} }}} \right. \kern-\nulldelimiterspace} {{\left( {{\text{cv}}\,{\text{of}}\,{\text{SUV}}} \right)}^{2} }} \right)}^{{1 \mathord{\left/ {\vphantom {1 2}} \right. \kern-\nulldelimiterspace} 2}}$$" align="middle" border="0">. Hence, for cv’s of SUVs below ∼1/3 improvements over tradition are possible, leading to F’s<0.95. Accounting additionally for height, as in SUV_bsa, gives very little improvement over the simplified approach here and gives essentially the same F’s as SUV _m . Conclusions Introduced here is a weight index useful in reducing variability and further understanding the SUV. Addressing weight sensitivity is appropriate where the cv of the SUVs is below about 1/3. Proposed is the very simple approach of using an average of an adult patient’s weight and ∼70 kg for FDG SUV calculations. Unlike other approaches the dimensionless population average of SUV _m s is unchanged from tradition.     

Loading 3-deazaneplanocin A into pegylated unilamellar liposomes by forming transient phenylboronic acid-drug complex and its pharmacokinetic features in Sprague-Dawley rats

3-Deazaneplanocin A (DZNep) is an attractive epigenetic anticancer agent through the inhibition of the cellular enhancer of zeste homolog 2 (EZH2) protein. The purpose of this study was to improve the pharmacokinetic characteristics of DZNep in vivo through developing a unilamellar pegylated liposomal formulation encapsulating DZNep (L-DZNep). A remote-loading method in the presence of phenylboronic acid (R-w-PBA) was developed to stably encapsulating DZNep inside liposomes (encapsulation efficiency = 50.7% at molar ratio of 1:10 of drug to lipids) through forming a transient PBA-DZNep complex. The pharmacokinetics of L-DZNep was investigated in Sprague-Dawley rats. In comparison with free drug, encapsulation of the DZNep in pegylated liposomes resulted in 99.3% reduction of the plasma clearance, whereas it increased the elimination half-life from 1.1 h to 8.0 h and the area under the plasma concentration curve by 138-fold. These findings demonstrate a novel approach (R-w-PBA method) through the development of L-DZNep, which may be extensively applied for the encapsulation of hydrophilic nucleoside analogs containing vicinal hydroxyl groups and protonable amino in the pegylated liposomes. Additionally, the pegylated liposomes could effectively prolong the retention of DZNep in the systemic circulation and therefore is highly likely to increase the DZNep’s tumor localization.     

Correlation of PET standard uptake value and CT window-level thresholds for target delineation in CT-based radiation treatment planning

PURPOSE: To develop standardized correlates of [18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) standard uptake value (SUV) to computed tomography (CT)-based window and levels. METHODS AND MATERIALS: Nineteen patients with non-small-cell lung cancer who underwent imaging with positron emission tomography (PET) and CT were selected. A method of standardizing SUV within CT planning software was developed. A scale factor, determined by a sensitivity calibration of the PET scanner, converts voxel counts to activity per gram in tissue, allowing SUVs to be correlated to CT window and levels. A method of limiting interobserver variations was devised to enhance "edges" of regions of interest based on SUV thresholds. The difference in gross tumor volumes (GTVs) based on CT, PET SUV >or= 2.5, and regions of 40% maximum SUV were analyzed. RESULTS: The mean SUV was 9.3. Mean GTV volumes were 253 cc for CT, 221 cc for SUV >or= 2.5, and 97 cc for SUV40%Max. Average volume difference was -259% between >or=2.5 SUV and CT and -162% between SUV40%Max and CT. Percent difference between GTV >or= 2.5 SUV and SUV40%Max remained constant beyond SUV > 7. For SUVs 4-6, best correlation among SUV thresholds occurred at volumes near 90 cc. Mean percent change from GTVs contoured according to CT (GTV CT) was -260% for GTV2.5 and -162% for GTV40%Max. Using the SUV40%Max threshold resulted in a significant alteration of volume in 98% of patients, while the SUV2.5 threshold resulted in an alteration of volume in 58% of patients. CONCLUSIONS: Our method of correlating SUV to W/L thresholds permits accurate displaying of SUV in coregistered PET/CT studies. The optimal SUV thresholds to contour GTV depend on maximum tumor SUV and volume. Best correlation occurs with SUVs >6 and small volumes <100 cc. At SUVs >7, differences between the SUV threshold filters remain constant. Because of variability in volumes obtained by using SUV40%Max, we recommend using SUV >or= 2.5 for radiotherapy planning in non-small-cell lung cancer.     

Gastric GIST malignancy evaluated by 18FDG-PET as compared with EUS-FNA and endoscopic biopsy

Objective. The usefulness of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸FDG-PET), whose high rate of FDG accumulation indicates high metabolism and malignant potential, has already been reported. The aims of this study were to evaluate the malignancy of primary gastrointestinal stromal tumour (GIST) in the stomach by ¹⁸FDG-PET and to correlate the FDG uptake values with known risk factors as determined by histology after EUS-guided fine needle aspiration (EUS-FNA) or endoscopic biopsy. Material and Methods. Of 29 patients with histologically proven GI-mesenchymal tumours, 21 with gastric GISTs underwent ¹⁸FDG-PET. Tumour size, mitotic index, Ki-67 labelling index (LI) and cellularity of the tumour tissue were compared with the standardized uptake value (SUV) of FDG. Results. Strong correlations were found between the SUV of FDG and EUS size, and mitotic index of EUS-FNA specimens (tumour size versus SUV, p=0.004, r=0.542; number of mitotic cells versus SUV, p=0.0078; n=21). Moreover, we examined the association between SUV and risk categories based on EUS-FNA findings using ROC curves. The cut-off values of FDG SUV were 2.2, 4.2 and 6.5 for the very low-, low-, intermediate- and high-risk groups, respectively. Conclusions. ¹⁸FDG-PET may be used to assess malignancy of GISTs. This image modality helps us determine the management strategy for these patients and complements the information on the biological behaviour and cellular proliferation of the tumours.