Count Density Ratios Research Articles

Thrombosis density ratio can predict the occurrence of pulmonary embolism and post-thrombotic syndrome in lower-extremity deep vein thrombosis patients.

Deep vein thrombosis (DVT) formation of lower extremities can lead to serious complications including pulmonary embolism (PE) and chronic post-thrombotic syndrome (PTS). We aimed to explore the relationship between the ratio of thrombotic density and the occurrence of PE and PTS in patients with DVT of the lower extremities. A retrospective analysis was conducted in patients who performed computed tomography venography, dividing into DVT with PE group (54 patients) and DVT-alone group (34 patients), The clinical data were recorded. Univariate and multivariate logistic regression analysis were used to analysis variables associated with PE. The ability of thrombosis density ratio and Wells score to diagnose PE was evaluated by using the receiver operating characteristic curve (ROC) area under the curve (AUC). According to the treatment and follow-up results, subgroup analysis was performed, and the Villata score was used to determine the presence or absence of PTS and its severity. Compare with the DVT-alone group, more patients had dyspnea and chest pain in the DVT with PE group. DVT with PE group had lower the percentage of neutrophils, white blood cell count and platelet count, while had higher blood cell count, D-dimer, wells score, thrombus and thrombus density ratio. Multivariate logistic analysis showed that percentage of neutrophils (OR(95% CIs)=1.15 (1.01,1.31), P = 0.040), platelets (OR(95% CIs)=0.96 (0.93,0.99), P = 0.011), and thrombus density ratio (OR(95% CIs)=5.99 (1.96,18.35), P = 0.002) are independent predictors of PE. The Wells score and thrombosis density ratio were consistent in the diagnostic efficacy of PE. In the subgroup analysis, there was a relevance between the ratio of thrombosis density and the Villalta score. Percentage of neutrophils, platelets, and thrombus density ratio are independent predictors of PE. The thrombosis density of DVT patients may be an index to predict the risk of PE and PTS in DVT patients.

Reference LINE-1 insertion polymorphisms correlate with Parkinson’s disease progression and differential transcript expression in the PPMI cohort

Long interspersed nuclear element-1 (LINE-1/L1) retrotransposons make up 17% of the human genome. They represent one class of transposable elements with the capacity to both mobilize autonomously and in trans via the mobilization of other elements, primarily Alu and SVA elements. Reference LINE-1 elements are, by definition, found in the reference genome, however, due to the polymorphic nature of these elements, variation for presence or absence is present within the population. We used a combination of clinical and transcriptomic data from the Parkinson’s Progression Markers Initiative (PPMI) and applied matrix expression quantitative trait loci analysis and linear mixed-effects models involving 114 clinical, biochemical and imaging data from the PPMI cohort to elucidate the role of reference LINE-1 insertion polymorphism on both gene expression genome-wide and progression of Parkinson’s disease (PD). We demonstrate that most LINE-1 insertion polymorphisms are capable of regulating gene expression, preferentially in trans, including previously identified PD risk loci. In addition, we show that 70 LINE-1 elements were associated with longitudinal changes of at least one PD progression marker, including ipsilateral count density ratio and UPDRS scores which are indicators of degeneration and severity. In conclusion, this study highlights the effect of the polymorphic nature of LINE-1 retrotransposons on gene regulation and progression of PD which underlines the importance of analyzing transposable elements within complex diseases.

Antihypertensive drugs may not delay the symptom progression of Parkinson’s disease: A 2-year follow-up study

BackgroundParkinson's disease (PD) is one of the most common neurodegenerative disease, and half of PD patients have hypertension as well. The effect of antihypertensive drugs on the progression of PD has been less studied. The focus of this study was on the changes in dopamine transporter (DAT) levels to assess the effect of antihypertensive drugs on the progression of PD. MethodsData from 321 drug-naïve patients from the Parkinson's Disease Progression Marker Initiative (PPMI) were collected over a 2-year period. Patients were divided into the PD with arterial hypertension (AH) group (102 cases) with antihypertensive drugs, the PD with other cardiovascular risk factors (CVRFs) group (60 cases) with antidiabetic and/or lipid-lowering drugs, and the pure PD group (159 cases) without CVRFs. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr (H&Y) stage were used to assess progression. DAT semiquantitative values were used to evaluate damage to dopaminergic neurons in the substantia nigra, including the contralateral and ipsilateral count density ratio and asymmetry index. ResultsThere were no significant differences among the three groups in MDS-UPDRS score and H&Y stage. Changes in DAT levels among the three groups were without distinct differences in the first year and second year. In each group, DAT decreased more in the first year than in the second year. There was no decrease in DAT uptake in the PD with AH group compared with the other groups during the follow-up period. ConclusionsThere is no evidence that antihypertensive drugs can delay PD progression within 2 years.

Gastrointestinal nematode and lungworm infections in organic dairy calves reared with nurse cows during their first grazing season in western France

The rearing system of dairy calves with nurse cows has been developing since 2010 in organic farms in western France. This system allows cow-calf contact until a weaning age close to the natural weaning for cattle and is characterized by an early turnout for calves at around one month of age with their nurse cows and a first grazing season with mixed grazing of calves and adults at a ratio of 2–4 calves per nurse cow. The objectives of this study were to assess the gastrointestinal (GIN) and lungworm infections in such reared calves and their variability during the first grazing season. Faecal egg count (FEC), pepsinogen (PEP) concentration and Ostertagia ELISA optical density ratio (ODR) were determined in calves (n = 497) at housing in 33 groups from 24 farms in 2018, and in calves (n = 405) and nurse cows (n = 199) throughout the 2019 grazing season in 41 groups from 20 farms. For lungworm infection, information was obtained during 2019 through the recording of coughing episodes along the grazing season and the Dictyocaulus ELISA ODR determination at housing both in calves and nurses. Results indicated that the level of GIN infection was overall low for calves during the first grazing season with PEP and Ostertagia ODR group-average values ranging from 0.97 to 1.6 U Tyr and 0.23 to 0.71 ODR respectively. No anthelmintic treatment being given in any group of calves. Ostertagia ODR values increased with the duration of the grazing season (>240 d) and with the ratio calves/nurse (>2). GIN parameters for nurses remained fairly stable during the grazing season with mean FEC, PEP and Ostertagia ODR group-average values of 13 epg, 2.28 U Tyr and 0.81 ODR, respectively. Antibodies against lungworms were detected in 3–62 % of calves depending on the duration of grazing, but only 6% of calves showed a coughing episode. The dilution effect due to the mixed grazing of resistant (nurse cows) and susceptible (calves) animals associated with predominant milk diet of calves during the first months of grazing in combination with protective grazing management allow calves to be turned out at an early age without using anthelmintic treatments. Further studies are needed to assess the GIN infection dynamics during the second grazing season in weaned heifers.

Chelation-Tamoxifen Conjugates for Imaging of Estrogen Receptors.

Background: The differential diagnosis of estrogen receptor-positive (ER+) pathway-activated systems by using a labeled antiestrogen helps to select the patients for optimal response to endocrine therapy and to discontinue the treatment when resistance occurs. The authors' purpose was to synthesize chelator-tamoxifen conjugates for imaging ER (+) diseases. Materials and Methods: A hydroxypropyl linker was incorporated between either cyclam or cyclam diacetic acid and tamoxifen analog to produce SC-05-L-1 (Z-1-(1,4,8,11-tetraazacyclotetradecan-1-yl)-3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)propan-2-ol) and SC-05-N-1 (Z-2,2'-(4-(3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)-2-hydroxy-propyl)-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)diacetic acid), respectively. In vitro cell uptake and cell/media ratios of 99mTc-SC-05-L-1 and 99mTc- SC-05-N-1 in ER (+) ovarian cancer cells (TOV-112D and OVCAR3) were performed. To ascertain the specificity of cell uptake, the cell uptake was blocked with estrone. In vivo 99mTc-SC-05-L-1 or 99mTc-SC-05-N-1 single-photon emission computed tomography/computed tomography was conducted in tumor-bearing rodents and compared to 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/magnetic resonance imaging (a reference technology). Results: The radiochemical purities of 99mTc-SC-05-L-1 and 99mTc-SC-05-N-1 were greater than 99% (n = 10). 99mTc-SC-05-L-1 had higher cell/media ratios than 99mTc-SC-05-N-1 in OVCAR-3 ER (+) cells. The cell uptake of 99mTc-SC-05-L-1 was blocked 80% by estrone indicating an ER-mediated process occurred. 99mTc-SC-05-N-1 was further selected for in vivo imaging studies due to higher maximum tolerated dose and superior water solubility than 99mTc-SC-05-L-1. 99mTc-SC-05-N-1 showed higher tumor uptake and tumor/muscle count density ratios than 18F-FDG in tumor-bearing rodents. Conclusion: 99mTc-SC-05-N-1 showed better differential diagnosis of ovarian tumors than 18F-FDG, indicating great promising in chelator-tamoxifen conjugate for ER pathway-directed systems imaging.

DIRECT COMPARISON BETWEEN DIFFUSION-WEIGHTED MRI AND PET/CT WITH [11С]METHIONINE IN PATIENTS WITH CEREBRAL GLIOMAS

The aim of the study was to assess the diagnostic value of MR diffusion imaging (DWI) and hybrid positron emission and computed tomography (PET/CT) with [11C]methionine for glioma grading and to compare the spatial distribution of diffusion restriction and [11C]methionine uptake abnormalities within a tumor.Material and methods: MRI with diffusion sequences and PET/CT with [11C]methionine were performed for 46 patients with untreated histologically proven brain gliomas. Quantitative evaluation included the minimal apparent diffusion coefficient value (ADCmin) in the tumor and maximum [11C]methionine uptake ratio, measured as ratio of highest tumor count density to that of the brain cortex(tumor-to-cortex-T/Cmax). Mean measurements of ADC (ADCmean) and T/C (T/Cmean) were obtained for each tumor. The ADC and T/Cratio values for glioma grading were assessed and correlations were evaluated. In addition PET and ADC images were coregistered to each other.Results: The T/Cmax and ADCmin values were significantly negatively correlated (r=–0,82). The T/Cmean and ADCmean measurements also demonstrated the significant negative correlation (r=0,56). The T/Cmax showed best accuracy in glioma grading. Sites of maximal radiotracer uptake and minimal ADC did not match in 34% of cases and in 66% of tumors the match was partial.Conclusion: Diagnostic accuracy of PET/CT using [11C]methionine in glioma grading exceeds DWI-MRI, and for both methods it is preferable to analyze a small tumor volume. The T/C ratios and ADC measurements demonstrate the significant inverse correlations. High rate of mismatch between spatial distribution of increased [11C]methionine uptake and low ADC areas within a tumor could be a result of different biological features registered by PET and DWI.

Effect of resolution recovery using graph plots on regional cerebral blood flow in healthy volunteers.

We evaluated the effect of resolution recovery (RR) using graph plots on regional cerebral blood flow (rCBF) in brain perfusion single-photon emission computed tomography (SPECT) images derived from healthy volunteers and patients diagnosed with probable Alzheimer's disease. We acquired brain perfusion SPECT images with scatter correction (SC), computed tomography-based attenuation correction (CTAC), and RR from a three-dimensional brain phantom and from healthy volunteers. We then compared contrast-to-noise ratio, count density ratios, increase maps, and rCBF using statistical parametric mapping 8. Regional brain counts were significantly increased from 20-24% with SC, CTAC, and RR compared with SC and CTAC. Mean CBF in healthy volunteers was 42.5±5.4mL/100g/min. Average rCBF determined using SC, CTAC and RR increased 7.5, 2.0, and 3.7% at the thalamus, posterior cingulate, and whole brain, respectively, compared with SC and CTAC. Resolution recovery caused variations in normal rCBF because counts increased in cerebral regions.

Initial Experience with Renal Denervation for the Treatment of Resistant Hypertension - The Utility of Novel Anesthetics and Metaiodobenzylguanidine Scintigraphy (MIBG).

Background:The Symplicity-HTN 3 trial failed to show significant difference in blood pressure (BP) lowering between patients undergoing catheter-based renal denervation (RDN) and the sham-procedure arm of the study. However, there is still optimism about the role of RDN in the treatment of resistant hypertension, because identification of patients with increased sympathetic activity thus being good RDN responders, improvements in the RDN procedure and new technology RDN catheters are all expected to lead to better RDN results. We present our initial experience with RDN for the treatment of resistant hypertension, and the utility of novel anesthetics and cardiac 123I-metaiodobenzylguanidine scintigraphy (123I-MIBG).Methods and Results:Seven patients with resistant hypertension underwent RDN and were followed up for 6 months. MIBG was performed before RDN, in order to estimate sympathetic activity and predict the response to RDN. All patients were sedated with dexmedetomidine and remifentanil during RDN. All patients tolerated the procedure well, were hemodynamically stable and their peri-procedural pain was effectively controlled. A median of 7.6 ± 2.1 and 6 ± 1.4 ablations were delivered in the right and left renal artery respectively, making an average of 6.8 burns per artery. No peri-procedural or late complications - adverse events (local or systematic) occurred. At 6 months, mean reduction in office BP was -26.0/-16.3 mmHg (p=0.004/p=0.02), while mean reduction in ambulatory BP was -12.3/-9.2 mmHg (p=0.118/p=0.045). One patient (14.3%) was a non-responder. None of the cardiac 123I-MIBG imaging indexes(early and late heart-to-mediastinum (H/M) count density ratio, washout rate (WR) of the tracer from the myocardium) were different between responders and non-responders.Conclusion:Patients with resistant hypertension who underwent RDN in our department had a significant reduction in BP 6 months after the intervention. 123I-MIBG was not useful in predicting RDN response. Dexmedetomidine and remifentanil provided sufficient patient comfort during the procedure, allowing an adequate number of ablations per renal artery to be performed, and this could probably lead to improved RDN results.

Ductal carcinoma in situ and ductal carcinoma in situ with microinvasion: correlation of FDG uptake with histological and biological prognostic factors.

Several studies investigated the correlation between the intensity of fluorodeoxyglucose (FDG) uptake and some histological and biological characteristics in breast cancer. Ductal carcinoma in situ (DCIS) is generally thought to be a precursor lesion of invasive breast cancer. The aim of this study was to assess the correlation between FDG uptake values on positron emission tomography/computed tomography (PET/CT) with histological and biological prognostic factors in DCIS and ductal carcinoma in situ with microinvasion (DCIS-Mi). PET/CT images for initial staging of confirmed DCIS and DCIS-Mi patients, taken between July 2004 and December 2009, were reviewed retrospectively. Maximum standardized uptake values (SUVmax) and tumor background count density ratio on PET/CT were compared with tumor characteristics. Histological and biological prognostic factors included tumor size, nuclear grade, Van Nuys Prognostic Index, estrogen receptor, progesterone receptor, HER2, and Ki-67 index. In total, 87 lesions from 83 patients (all females; mean age 51±9years) were studied. The Van Nuys Prognostic Index group was 1 in 25 lesions, 2 in 36, and 3 in 26. On statistical analysis, significant differences in SUVmax and tumor background count density ratio were seen between the Van Nuys Prognostic Index groups and according to tumor size and HER2. The correlation between SUVmax and Ki-67 was significant. However, the correlation between tumor background count density ratio and Ki-67 was not statistically significant. In DCIS and DCIS-Mi cases, significant correlations were found between increased FDG uptake and several histological and biological factors for poor prognosis (tumor size, Van Nuys Prognostic Index, and HER2).

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing.

The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Correlation of 11C-methionine PET and diffusion-weighted MRI

11C-Methionine (MET) PET and diffusion-weighted (DW) MRI are commonly used for evaluation of gliomas. We assessed the correlation between MET uptake and diffusion restriction measured on DW MRI in glioma. Thirty-one patients with gliomas, who were initially examined with MET PET and DW MRI, were enrolled retrospectively. MET PET and apparent diffusion coefficient (ADC) images were coregistered to each other, using rigid-body transformation. Tumor-to-normal count density ratio of the cortex (TNR) and normalized apparent diffusion coefficient (nADC) value were measured for each voxel on the MET PET and ADC map. The maximum TNR (TNRmax) and minimum nADC (nADCmin) were obtained for each tumor. Correlations between those parameters were evaluated. The TNRmax and nADCmin values of a glioma were significantly correlated (r=-0.42). TNRmax and nADCmin were significantly correlated with glioma grades. Furthermore, TNRmax and nADCmin showed a trend for correlation with the Ki-67 index. We analyzed the correlation between voxel-based TNR and ADC within a tumor and observed no correlation between them. Regions with high MET uptake did not correspond with regions with low nADC. We found a negative correlation between TNRmax and nADCmin for each glioma; however, MET uptake and ADC within a tumor were independent of each other and were heterogeneous. The two parameters represent different biological features; thus, as a comprehensive approach, MET PET and DW MRI might have a complementary role in the characterization of gliomas.

Noninvasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: A prognostic tool for metastatic castration-resistant prostate cancer (CRPC).

11081 Background: PSMA is nearly universally expressed by PC, upregulated with increased grade and castration-resistance. Evidence points towards PSMA expression as a downstream cellular biomarker of androgen receptor (AR) activity and non-invasive measurement of PSMA expression has recently been demonstrated to be a novel biomarker of AR activity. Methods: Planar gamma camera images following radiolabeled J591 (111In-J591 or 177Lu-J591) were semi-quantitatively scored using 2 methods by 2 independent radiologists blinded to outcome.A 5-point visual score (VS) of 0 - 4+ was assigned. Tissue Targeting Index (TTI), a novel metric designed to semi-quantitatively score images was calculated using the ratio of lesion count density (corrected for background) to whole body count density, with maximum (TTImax) and mean (TTIave) scores recorded. Follow up tabulating subsequent therapies and overall survival (OS) was recorded and imaging scores were associated with OS using Cox regression analysis. Results: 130 men with metastatic CRPC underwent radiolabeled J591 imaging. 86.2% had bone metastases, 51.5% lymph node, 16.9% lung, 9.2% liver. 87.7% had accurate targeting of known sites of disease by planar imaging. CALGB (Halabi) nomogram scores were prognostic for the population. As continuous variables, TTImax (p=0.013) and TTIave (p=0.002) were associated with worse survival. VS demonstrated a trend for worse survival (p=0.09). In multivariate analysis, TTI maintained independent prognostic value when controlling for Halabi score: TTImax HR 1.05 [95% CI 1.01, 1.10; p=0.02], TTIaveHR 1.09 [1.03, 1.16; p=0.004]. Conclusions: Level of PSMA expression measured by planar gamma-camera imaging following radiolabeled J591 is associated with OS in men with metastatic CRPC. High PSMA expression may indicate more aggressive tumor biology with increased AR pathway dysfunction. Improvements in quantitative molecular imaging techniques such as PSMA PET/CT with 89Zr-J591 may prove to be a valuable prognostic and predictive biomarker, particularly in the setting of AR- and PSMA-targeted therapy. Clinical trial information: NCT00195039, NCT00538668.

Abstract 4696: Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy.

Abstract Background: PSMA is nearly universally expressed by prostate cancer and is upregulated with castration-resistance. Recently, non-invasive measurement of PSMA expression has been demonstrated to be a novel biomarker of androgen receptor activity in animal models. J591 is a monoclonal antibody which selectively and efficiently binds the external domain of PSMA with no direct effect on PSA expression or secretion. Four therapeutic phase I and II trials of radiolabeled (RL)-J591 using (177Lu-J591 and 90Y-J591) have been performed in men with metastatic castration-resistant prostate cancer (CRPC). In addition to therapeutic infusion with RL-J591, planar gamma camera imaging was performed. Methods: Following IRB approval, a combined analysis of 4 prospective studies of RL-J591 for metastatic CRPC was performed. RL-J591 images were semi-quantitatively scored using 2 methods by 2 independent radiologists blinded to outcome. A 5-point visual score (VS) of 0 - 4+ was assigned. In addition, a semi-quantitative Tissue Targeting Index (TTI) was calculated for the most prominent lesions in each subject using the ratio of lesion count density (corrected for background) to whole body count density, with maximum and mean scores recorded. PSMA expression as measured by imaging was correlated with efficacy measures in long-term follow up of all studies. Results: 130 patients (pts) with metastatic CRPC received RL- J591 with semi-quantitative imaging. 86.2% had bone metastases, 51.5% lymph node, 16.9% lung, 9.2% liver. 87.7% had accurate targeting of known sites of disease by planar imaging. Only 8.0% of pts with no evidence of PSMA expression via J591 imaging (VS=0) experienced treatment response versus 40.6% of those with the highest strongest expression as measured by VS (p=0.01). In addition to PSA declines, for the subset of 17 pts with baseline and follow up circulating tumor cell (CTC) counts, those with higher VS tended to have more CTC decreases (p=0.12). Those with the lowest level of PSMA expression as measured by TTI tended to have fewer PSA declines (p=0.12). PSA response was associated with superior overall survival compared to those without >30% PSA decline (p=0.02). Conclusions: Non-invasive measurement of PSMA expression may be semi-quantitatively measured with planar gamma-camera imaging following infusion with RL-J591. Level of PSMA expression is associated with response to radiolabeled anti-PSMA radioimmunotherapy. Improvements in quantitative molecular imaging techniques such as PSMA PET/CT with 89Zr-J591 may prove to be a valuable predictive biomarker for PSMA-based therapeutics. Citation Format: Naveed H. Akhtar, Joseph Osborne, David M. Nanus, Shankar Vallabhajosula, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa. Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4696. doi:10.1158/1538-7445.AM2013-4696

99mTc-N4amG: Synthesis biodistribution and imaging in breast tumor-bearing rodents

99mTc-N4-guanine (99mTc-N4amG) was synthesized and evaluated in this study. Cellular uptake and cellular fraction studies were performed to evaluate the cell penetrating ability. Biodistribution and planar imaging were conducted in breast tumor-bearing rats. Up to 17%ID uptake was observed in cellular uptake study with 40% of 99mTc-N4amG was accumulated in the nucleus. Biodistribution and scintigraphic imaging studies showed increased tumor/muscle count density ratios as a function of time. Our results demonstrate the feasibility of using 99mTc-N4amG in tumor specific imaging.

Very low-activity stress/high-activity rest, single-day myocardial perfusion SPECT with a conventional sodium iodide camera and wide beam reconstruction processing

BackgroundA stress (S)/rest (R) 1-day Tc-99m sestamibi protocol is logistically advantageous and facilitates stress-only imaging. However, with conventional 370 MBq (10 mCi) S activity and subsequent 1,110-1,295 MBq (30-35 mCi) R activity there is a risk of S-to-R “shine-through” and underestimation of defect reversibility. New software methods cope with lower counting statistics and should allow for both a reduced S activity and also less likelihood of S-to-R “shine-through.” Methods102 prospective patients [49 men, 53 women; mean weight 178 ± 41 lbs (range 98-265 lbs); chest 41.5″ ± 4.0″ (range 32″-52″)] received 192.4 + 18.5 MBq (5.2 ± 0.5 mCi) Tc-99m sestamibi S (25 exercise, 77 regadenoson) activity followed in 30-40 minutes by “full-time” (12 minutes) two-headed NaI camera S SPECT. Immediately thereafter, a 16-minute S SPECT acquisition was also performed in 37/102 patients. Then at 60-80 minute post-S all patients received 1328.3 + 129.5 MBq (35.9 ± 3.5 mCi) Tc-99m sestamibi, and “half-time” (7.5 minutes) R SPECT was acquired. All tomograms were processed with wide beam reconstruction (WBR, UltraSPECT Ltd.) software. A time-adjusted R/S myocardial count density ratio (MCDR) was calculated using automated software. S SPECT quality was visually graded (poor, fair, good, excellent) based upon myocardial definition, cavity contrast, RV visualization, and noise. For comparison, the S/R MCDR was calculated in 581 consecutive patients undergoing a conventional 370 MBq R/1110 MBq S (10 mCi R/30 mCi S) protocol. ResultsS SPECT was normal in 44 patients (43%). Image quality was good-excellent in 93 (91%) patients with 12-minute S SPECT. Also in 37 (98%) patients with 16-minute S SPECT, quality was good-excellent. In patients with >42″ chests 12-minute S SPECT quality worsened with increasing chest circumference, manifested by myocardial “blurring.” Image quality improved by ≥1 grade in the 12/37 patients (32%) also undergoing 16-minute S SPECT. The time- and decay-corrected 12-minute mean R/S MCDR was 5.78, a ratio adequate to minimize S-to-R shine-through, as verified in phantom experiments, and significantly better than a 3.79 S/R ratio achieved in the 581 patients undergoing a conventional R/S protocol. ConclusionsAn approximately 185 MBq (5 mCi S) Tc-99m SPECT processed with WBR provides adequate image quality. For larger patients prolonging image acquisition to 16 minutes is beneficial. For patients with normal S SPECT, a S-only protocol is feasible, affording them a very low (approximately 1.4 mSv) radiation dose. If subsequent R SPECT is necessary, it can be performed with approximately 1,332 MBq (36 mCi) with minimal S-R “shine-through.”

Diagnostic Value of 11C-Methionine (MET) and 18F-Fluorothymidine (FLT) Positron Emission Tomography in Recurrent High-Grade Gliomas; Differentiation from Treatment-Induced Tissue Necrosis

We retrospectively evaluated the usefulness of combined measurement of L-methyl-[11C]methionine (MET) and 3'-deoxy-3'-[18F]fluorothymidine (FLT) positron emission tomography (PET) in the differential diagnosis between recurrent gliomas and necrotic lesions. Twenty-one patients with high-grade glioma, previously treated with surgery and radiotherapy with chemotherapy and first radiological suspicion of recurrence were enrolled. The uptake was assessed by the maximum standardized uptake value (SUVmax) and lesion-to-normal tissue count density ratio (L/N ratio). Of the 21 lesions, 15 were diagnosed recurrent gliomas and six were necrotic lesions. The average SUVmax was not significantly different between recurrent gliomas and necrotic lesions on either MET-PET or FLT-PET. The average L/N ratio of recurrent gliomas (3.36 ± 1.06) was significantly higher than that of necrotic lesions (2.18 ± 0.66) on MET-PET (p < 0.01) and the average L/N ratio of recurrent gliomas (7.01 ± 2.26) was also significantly higher than that of necrotic lesions (4.60 ± 1.23) on FLT-PET (p < 0.01). ROC curve analysis showed that the areas under the curves were high but not different between MET- and FLT-PET. PET studies using MET and FLT are useful in the differentiation of recurrent glioma from treatment-induced necrotic lesion. However, there is no complementary information in the differentiation with simultaneous measurements of MET- and FLT-PET.

Development of -N4-NIM for Molecular Imaging of Tumor Hypoxia

The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4,8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for 99mTc. The present study was aimed to develop 99mTc-cyclam-2-nitroimidazole (99mTc-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of 99mTc-N4-NIM and 99mTc-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of 99mTc-N4-NIM was evaluated in breast-tumor-bearing rats at 0.5–4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of 99mTc-N4-NIM was >96% by HPLC. Cell uptake of 99mTc-N4-NIM was higher than 99mTc-N4 in both cell lines. Biodistribution of 99mTc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6–10 mmHg compared to 40–50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with 99mTc-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. 99mTc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.

GATE based Monte Carlo simulation of planar scintigraphy to estimate the nodular dose in radioiodine therapy for autonomous thyroid adenoma

The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400 Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE. The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms “Adult Female” (AF, 16 ml thyroid) and “Adult Male” (AM, 19 ml thyroid) were used as source regions. Nodules of 1 ml and 3 ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias. The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1 ml nodule) to 15.3 (AM, 3 ml nodule). Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1 ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM). For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r 2 > 0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM. The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post-therapeutic scintigraphy.

Development of 68Ga‐Glycopeptide as an Imaging Probe for Tumor Angiogenesis

Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP) in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel) of the tumor and muscle (at the symmetric site) was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV) for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis.

FOCAL SKELETAL MUSCLE UPTAKE OF 99mTECHNETIUM-HYDROXYMETHYLENE Diphosphonate FOLLOWING PERONEAL NERVE BLOCKS IN HORSES

We have observed focal skeletal muscle uptake of 99mTechnetium-hydroxymethylene diphosphonate (Tc-HDP), which could mimic a tibial lesion, in horses following peroneal nerve blocks. To characterize this observation further, 45 bone phase scintigrams were performed in 12 horses undergoing peroneal nerve blocks. Scans were performed before, and 1, 3, 7, and 14 days postblock. The superficial and deep branches of the peroneal nerve were blocked by injecting 10 ml of 2% mepivacaine in one limb and 20 ml in the other. Images were evaluated for uptake at the block site and uptake likely to mimic a tibial lesion. Regions of interest were placed over the block site and distal tibia. Count density ratios were used to estimate change in uptake intensity over time. The overall proportion affected was 0.52 (95% confidence interval [CI], 0.36-0.68; P < 0.001) 1 day postblock and 0.24 (95% CI, 0.13-0.40; P = 0.005) 3 days postblock. The overall proportion likely to mimic a tibial lesion was 0.19 (95% CI, 0.09-0.33; P < 0.001) 1 day postblock and 0.21 (95% CI, 0.09-0.40; P = 0.005) 3 days postblock. Focal skeletal muscle uptake was seen in only one horse 7 days postblock. Increased uptake intensity was associated with higher local anesthetic dose (P = 0.042). Peroneal nerve blocks cause focal skeletal muscle uptake of 99mTc-HDP on bone phase scintigraphy. This occurs in approximately 50% of blocked limbs and can mimic a tibial lesion on the lateral view in approximately 20% of blocked limbs.