Administration Of 18F-FDG Research Articles

Intramuscular [18F]F-FDG Administration for Successful PET Imaging of Golden Hamsters in a Maximum Containment Laboratory Setting.

Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After [18F]F-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time-activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection, [18F]F-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of [18F]F-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting.

Assessment of extremity exposure to technologists working manually with 99mTc-labelled radiopharmaceuticals and with an automatic injection system for 18F-FDG

The hands of nuclear medicine (NM) personnel involved in radiopharmaceutical preparation and administration can receive significant radiation doses. The dose distribution across the hand is nonuniform and the Hp(0.07) doses obtained by an individual passive ring dosimeter do not always present a real situation. The aim of this study was to assess the extremity exposure of NM workers working with 99mTc-labelled radiopharmaceuticals and with an automatic IRIDE (COMECER, Italy) 18F-FDG injection system. Hp(0.07) doses were measured using calibrated thermoluminescent dosimeters-100 (TLD-100) and were read by a RIALTO TLD (NE Technology) reader. It was found that the most exposed parts of the hand during work with 18F and 99mTc radionuclides are the fingertips of the thumb, index finger and middle finger. The maximum fingertip doses were 1.3–2.4 times higher compared with the doses from the typical monitoring position (base of the middle finger of the dominant hand). When working with 99mTc, the average hand doses were relatively high, i.e. 0.17 ± 0.04 and 0.37 ± 0.13 mSv Gbq−1 for the left and the right hand, respectively, during preparation, and 58 ± 20 and 53 ± 13 µSv GBq−1 for the left and the right hand, respectively, during administration of 99mTc labelled radiopharmaceuticals. Meanwhile, the lowest doses were found for hands during administration of 18F-FDG (average hand dose 28 ± 13 µSv GBq−1 for the left hand and 28 ± 7 µSv GBq−1 for the right hand), which shows the advantages of automated injection/infusion systems, thus implementation of automatic infusion/injection in hospitals could be an expedient way to optimize Hp(0.07) doses to NM workers.

18F-FDG Fetal Dosimetry Calculated with PET/MRI.

The fetal absorbed dose from 18F-FDG administration to the mother is an essential piece of information when considering the use of PET to stage cancers during pregnancy. However, the few existing human case reports were obtained using either PET-only or PET/CT machines, which may not accurately identify the soft tissues of the fetus for dosimetric calculations. This study presents data from 11 women injected with 18F-FDG for cancer staging during the first 2 trimesters of pregnancy and is, to our knowledge, the first to be entirely acquired with PET/MRI. Methods: Eleven pregnant women (12 scans) with cervical cancer were imaged with 18F-FDG PET/MRI, and their images were retrospectively analyzed for this study. The fraction of injected activity concentrated by the fetus was derived from manually drawing regions of interest on the MRI slices. From the activity fraction, the fetal time-integrated coefficients were derived and combined with the standard coefficients of the mothers' organs from the ICRP publication 106. The fetal absorbed doses were calculated with OLINDA/EXM 1.1 and a dynamic bladder model. Results: All fetuses after early pregnancy could be accurately delineated because of the coregistered MRI scans. 18F-FDG activity was unevenly distributed in the fetal body: the hearts and urinary bladders were generally visible, whereas the brain showed lower uptake. The estimated fetal doses were 2.21E-02 mGy/MBq for 1 woman imaged in early pregnancy, 7.38 ± 0.25 E-03 mGy/MBq for 3 women imaged at the end of the first trimester, and 4.92 ± 1.53 E-03 mGy/MBq for 8 women imaged during the second trimester. Conclusion: PET/MR images of pregnant women injected with 18F-FDG confirm that the fetal 18F-FDG dose is very low. Therefore, clinically appropriate 18F-FDG scans in women with cancer should not be withheld because of pregnancy.

Noninvasive estimation of human radiation dosimetry of 18F-FDG by whole-body small animal PET imaging in rats

PurposeSmall animal PET provides the biodistribution of administrated radiotracer in vivo and have a potential to contribute on dosimetry study. The aim of this study is to investigate the effect of region-of-interest (ROI)-delineation in whole-body rat PET image toward non-invasive estimation of human dosimetry of 18F-FDG. MethodAfter administration of 18F-FDG (averaged 11.7 MBq), 3.5-h PET and 20-min CT scans were sequentially performed for three rats by Clairvivo PET/CT system. Seven source organs, and the remainder of the body, were studied to extrapolate %ID(t) and estimate time-integrated activity coefficients [kBq-h/MBq] in human. The mean absorbed dose in each target organ and the effective dose were estimated by MIRD method. Effects of ROI-definitions on both extrapolated %ID(t) in human and estimated doses were also investigated by using (i) small ROIs of high uptake region and (ii) whole organ ROIs. ResultsAveraged effective doses of 18F-FDG in human by using high-uptake and whole-organ ROIs were 27.8 ± 6.54 and 19.3 ± 2.72 μSv/MBq, respectively. ConclusionThe use of small animal PET scanner, which allows repeatedly PET scans, have a potential to contribute on the reduction of the number of experimental animals. However, the ways of ROI drawing influences on the estimated effective dose and safe-side ROI definition may be preferred.

Transcatheter aortic valve replacement associated infective endocarditis case series: broadening the criteria for diagnosis is the need of the hour

BackgroundTranscatheter valve replacement (TAVR) is an important therapeutic intervention for patients with aortic valve stenosis. As TAVR has become available to a broader population, there has been an increase in the number of less common, yet potentially catastrophic, complications. TAVR related infective endocarditis (TAVR-IE) is a rare, but potentially fatal, complication.Case seriesWe present here two patients that we encountered for TAVR associated infective endocarditis. Our first patient presented 5 weeks after his TAVR. His initial presentation was consistent with signs of sepsis. The patient then developed Mobitz type I block during hospital course. His TEE was negative for features of infective endocarditis. Due to high suspicion, patient was taken for surgical exploration and was found to have multiple foci of vegetation adhered to the stent frame. Our second patient presented with new onset pulmonary edema, worsening heart failure and systemic inflammatory response. A TEE was done for persistent MSSA bacteremia which showed stable prosthetic valve function with no signs of infective endocarditis. Patient was discharged with a prolonged course of intravenous antibiotics. Patient was re-admitted for worsening sepsis and blood cultures were positive for MSSA. Patient was taken for surgical exploration of his prosthetic aortic valve which showed purulent aortic root abscess.ConclusionThrough these cases, we aim to raise awareness on TAVR-IE. Due to the atypical clinical presentation, the modified Duke criteria may not be sufficient to diagnose TAVR-IE. Transesophageal echocardiogram in TAVR-IE may be negative or indeterminate. Prosthetic valve shadow may obscure smaller vegetations and/or smaller abscesses. A negative transesophageal echocardiogram should not rule out TAVR-IE and further diagnostic imaging modalities should be considered. PET/CT after administration of 18F-FDG (fluorodeoxyglucose) is a useful diagnostic tool in the diagnosis of infective endocarditis where TEE has been negative or inconclusive. Multi-modal imaging, in addition to the modified Duke criteria, can facilitate early diagnosis and improved mortality outcomes.

18F-FDG PET in Myocardial Viability Assessment: A Practical and Time-Efficient Protocol.

We assessed image quality using a practical and time-efficient protocol for intravenous glucose loading and insulin injection before administration of 18F-FDG for PET myocardial viability evaluation in patients with ischemic cardiomyopathy (ICM), with and without type 2 diabetes mellitus. Methods: The metabolic preparation period (MPP) or optimal cardiac 18F-FDG uptake was determined from the time of intravenous infusion of 12.5 or 25 g of 50% dextrose to the time of 18F-FDG injection. Cardiac 18F-FDG image quality was evaluated according to a 5-point scoring system (from 5, excellent, to 1, nondiagnostic) by 2 independent observers. In cases of disagreement, consensus was achieved in a joint reading. Fifteen patients with ICM who underwent oral glucose loading and intravenous insulin administration served as a reference for MPP comparisons. Results: Fifty-nine consecutive patients (age, 63 ± 10 y; 48 men and 11 women) underwent rest 99mTc-tetrofosmin SPECT/CT and 18F-FDG PET/CT for the evaluation of myocardial viability. 18F-FDG image quality was scored as excellent in 42%, very good in 36%, good in 17%, fair in 3%, and nondiagnostic in 2%. When diabetic and nondiabetic patients were compared, the quality scores were excellent in 29% versus 76%, very good in 41% versus 18%, good in 24% versus 6%, fair in 4% versus 0%, and nondiagnostic in 2% versus 0%. The mean (±SD) quality score was 4.12 ± 0.95, and overall it was better in nondiabetic than in diabetic patients (4.71 ± 0.59 vs. 3.88 ± 0.96; P < 0.0001). Notably, the average MPP was significantly less with intravenous glucose loading than with oral glucose loading (51 ± 15 min vs. 132 ± 29 min; P < 0.0001), paralleled by higher insulin doses (6.3 ± 2.2 U vs. 2.0 ± 1.69 U; P < 0.001). Conclusion: Using a practical and time-efficient protocol for intravenous glucose loading and insulin administration before 18F-FDG injection reduces the MPP by 61% as compared with an oral glucose challenge and affords good-to-excellent image quality in 95% of ICM patients.

Myocardial Glucose Metabolism Is Increased in Newly Diagnosed Lung Adenocarcinoma

Background: Cardiac metabolism alterations may be involved in abnormalities of cancer patients’ cardiovascular system. This study aimed to explore whether left ventricular myocardial glucose metabolism is altered and its related factors in newly diagnosed patients with lung adenocarcinoma (LAD) who underwent fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT). Methods: From our ¹⁸F-FDG PET/CT imaging database, 171 patients with newly diagnosed LAD and 43 nononcologic subjects with matched age and sex were retrospectively analyzed. The included patients underwent conventional ¹⁸F-FDG PET/CT imaging with a >12-h fasting before ¹⁸F-FDG administration. The standardized uptake values (SUVs) of the left ventricular (LV) myocardium, arterial wall, epicardial adipose tissue (EAT), spleen, and bone marrow were separately measured. Laboratory parameters and echocardiographic results were collected as well. LAD patients were divided into 2 groups based on the 95th percentile of LV maximal SUV (SUV_max) obtained from the 43 nononcologic subjects. Univariate analysis and multiple logistic regression analysis were used to identify significant factors. Results: Higher LV SUV_max was found (3.8 [2.4, 7.7] vs. 3.0 [2.0, 5.4], p = 0.052) in LAD than that in nononcologic patients, whereas no significant differences of ¹⁸F-FDG uptake were found in the arterial wall, EAT, spleen, or bone marrow between LAD patients and controls. The maximum diameter (D_max) of the LAD lesion, SUV_max of spleen, and SUV_max of EAT were related to LV SUV_max in LAD. Conclusions: Myocardial glucose metabolism is increased in patients with newly diagnosed LAD. D_max of LAD lesion, spleen activity, and EAT activity contribute to the increased LV activity in LAD.

The image quality, lesion detectability, and acquisition time of 18F-FDG total-body PET/CT in oncological patients.

The purpose was to investigate the effects of short acquisition time on the image quality and the lesion detectability of oncological 18F-FDG total-body PET/CT. Nineteen oncological patients (6/13 women/men, age 65.6 ± 9.4years) underwent total-body PET/CT on uEXPLORER scanner using 3D list mode. The administration of 18F-FDG was weight-based (4.4MBq/kg). The acquisition time was 900s, and PET data were reconstructed into 900-, 180-, 120-, 60-, 30-, and 18-s duration groups. The subjective PET image quality was scored using a 5-point scale (5, excellent; 1, poor) in 3 perspectives: overall quality, noise, and lesion conspicuity. The objective image quality was evaluated by SUVmax and standard deviation (SD) of the liver, SUVmax of the tumor, and tumor-to-background ratio (TBR). The lesion detectability was the percentage of identifiable lesions in the groups of 180 to 18s using the group 900s as reference. Our results showed that sufficient and acceptable subjective image quality could be achieved with 60- and 30-s groups, and good image quality scores were given to 180- and 120-s groups without significant difference. For shortened acquisition time, SD was increased, while SUVmax of tumor and TBR remained unchanged. The lesion detectability was decreased with shorter acquisition time, but the detection performance could be maintained until the 60-s group compared with the 900-s group, although the image quality degraded. The total-body PET/CT can significantly shorten the acquisition time with maintained lesion detectability and image quality.

The role of 18FDG PET/CT imaging of aortic atherosclerosis: prospective study and technique optimization

BackgroundAtherosclerosis is an inflammatory disease of the inner wall of large and medium-sized arteries. The progress of atherosclerosis based on a lot of factors, including systemic involvement of disease, the precise vascular arterial affection, and the degree of flow obstruction. We aim in this study to estimate the FDG uptake of the aortic wall in the early and delayed imaging and to correlate this with the morphologic changes detected by CT.ResultsThis is a prospective study that was performed through 1 year. The study included 50 patients [30 males (60%) and 20 females (40%)] with male to female mean ratio 1.5:1 and their mean age 58.3 ± 15.7 years. Each patient underwent dual time-point 18F-FDG PET CT imaging at ~ 60 min (Early images) and 180 min (delayed images) after the administration of 18F-FDG. For each patient, the global 18F-FDG uptake in the aorta was determined by manually drawing regions of interest (ROIs) around the outer part of the arterial wall on every slice of the attenuation-corrected transverse PET CT images. Per-patient, per-time-point, per-vessel, and per-ROI radiotracer decay-corrected and body weight-corrected SUVs were calculated, resulting in a single mean value of maximum SUV for the aorta. The aortic wall FDG uptake was measured in both early and delayed images and expressed in terms of SUVmax. Then Retention index percentage of the aorta was measured. The retention index percentage was calculated by subtracting the SUVmax in early images from the SUVmax in delayed images and dividing by SUVmax in early images.ConclusionAortic wall FDG uptake can be used as an additional parameter as well as a biomarker on evaluation of the arterial atherosclerotic activity. Delayed post 3 h FDG imaging is more accurate than the routine early post 1 h imaging in evaluating the atherosclerotic activity.

Using of ¹⁸F-FDG to evaluate the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway: a PET-MRI pilot study

Objective:This study evaluated the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway via the instillation of ¹⁸F-FDG at the olfactory cleft. Method:Seven healthy volunteers and 5 patients with traumatic dysosmia were enrolled in the study. Subjects were all instilled with ¹⁸F-FDG on each side of the olfactory cleft under endoscopy. After 12 hours, a PET/MR scan was performed to track the metabolism pathway of ¹⁸F-FDG. Then, we compared the diameter of the olfactory bulb and the olfactory bulb intake between normal volunteers and patients with traumatic olfactory disorders. Result:In healthy volunteers, there was a significant difference in ¹⁸F-FDG uptake between the regions of interest in which ¹⁸F-FDG was or was not in contact with the cribriform plate（P=0.012 7）; this difference also existed in patients with traumatic olfactory disorders（P=0.038 1）. Patients with traumatic olfactory disorders did not exhibit significant differences in ¹⁸F-FDG uptake in the region of interest compared with healthy volunteers（P=0.937 2）. Conclusion:The olfactory bulb is obviously atrophied in patients with traumatic olfactory dysfunction, and the uptake of ¹⁸F-FDG in the olfactory bulb region of interest is also reduced. The administration of ¹⁸F-FDG via olfactory fissure area can enter olfactory bulb and parafrontal tissues through the nasal brain pathway,¹⁸F-FDG can enter the central nervous system through the nasal-brain pathway, which is not affected by olfactory nerve transection injury.

Impact of the Association between Tgl and EZH2 Mutations (Y641N/Y641F/Y641H/Y641S) on Disease Free Survival of Patients with Diffuse Large B-Cell Lymphoma

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Although PET/CT has allowed a better diagnostic evaluation in these patients, none metabolic index has been incorporated into prognostic scores, neither molecular markers have been associated with PET/CT findings. Aim: To define the association between PET/CT findings and EZH2 mutations, and their impact on survival of patients with DLBCL. Methods: Patients: A cohort study of newly diagnosed DLBCL patients. Cohorts were defined according to the presence of EZH2 (Y641N/Y641F/Y641H/Y641S) mutations. Clinical variables were: age, comorbidities, IPI score, bulky disease, clinical stage, serum albumin, LDH and B2-microglobulin levels, and ECOG. Histopathologic variables were GC (Germinal center) versus no-GC by Hans nomogram, BCL2, BLC6, &amp; MYC expression, as well as double-hit. All patients were treated with six cycles of standard RCHOP. PET/CT assessed parameters were: Total metabolic tumor volume (TMV), Total lesion glycolysis (TLG) and SUV max. Clinical response was evaluated by PET/CT, using Deauville's criteria. All 18F-FDG PET/CT scans were performed using the Biograph 16 PET/CT scanner (Siemens AG, Munich, Germany). Patients fasted for at least 6 h prior to intravenous (IV) administration of 18F-FDG (5.5 MBq/kg body weight) to ensure a serum glucose level of &lt;10 mmol/l. Methods: DNA was extracted from paraffin-embedded tissue. PCR analysis was carried out in a 2700 Thermalcycler (Applied Biosystems) to detect mutations in Exon 16 of EZH2; the sequencing and electrophoresis of PCR products was performed using ABI3100 genetic analyser. Sequences were compared with the EZH2 reference sequence (GenBank NG_032043.1). The protocol was approved by IRB (Approval number CEI/966/15). Statistics: After descriptive analysis, mean metabolic indexes were compared by ANOVA between patients with wt and any of the EZH2 mutations . Kaplan-Meier method was used to construct Disease-free survival (DFS) curves and the Log-rank test was used for comparisons. COR curves were used to evaluate metabolic indexes as risk factors infuencing on DFS. Results: Results: 230 patients (120 male), were included. Median age was 58.3 years (SD 14.25; range: 21-91); 169 of them (73.4%) had advanced disease and 224 (97.3%) had ECOG &lt;2. Absence of B symptoms or bulky disease was documented in 154 (67%) and 136 cases (59.1%), respectively. GC-type was found in 65%. Although sixty cases (26%) were considered to be DLBCL double expressor (MYC +BLC2 overexpression), only 15% were double-hit DLBCL. Mutations at codon 641, exon 16 of EZH2 were described in 15% of cases, as follows: Tyr 641 Asn (Y641N) [6 %],Tyr 641 Phe(Y641F) [6%], Tyr 641 His (Y641H) [3%] and Tyr 641Ser (Y641S) [1%]. Any clinical parameter was different between wt and any EZH2 mutations. However, regarding metabolic indexes by PET/CT, TLG was higher in EZH2 mutated patients (mean: 8314.02g [95 %CI: 5623-11004g]), in comparsion with wt patients (mean: 5228.99g, [ 95 % CI: 4114-6316g], p=0.02). Response was classified as complete in 75% of cases, partial in 3.5%, and progressive disease in 11%. The association of these mutations on DFS is shown in table 1. In addition, mean TLG and TMV indexes were lower in patients without relapse. (Table 2) Summary/Conclusion: These preliminary results suggest that patients with any of EZH2 (Y641F) mutations have a higher TLG by PET/CT at diagnosis, and both values have a negative impact on DFS of patients with DLBCL. Our results need to be confirmed on a larger sample and a longer follow-up. Disclosures No relevant conflicts of interest to declare.

Hybrid PET- and MR-driven attenuation correction for enhanced 18F-NaF and 18F-FDG quantification in cardiovascular PET/MR imaging

BackgroundThe standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging. MethodsWe introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD). ResultsIn rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication. ConclusionsKi-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.

Intratumoral 18F-FLT infusion in metabolic targeted radiotherapy

BackgroundThe goal of targeted radiotherapy (TRT) is to administer radionuclides to tumor cells, while limiting radiation exposure to normal tissues. 3′-Deoxy-3′-[18F]-fluorothymidine (18F-FLT) is able to target tumor cells and emits a positron with energy appropriate for local (~ 1 mm range) radiotherapy. In the present work, we investigated the potential of TRT with a local administration of 18F-FLT alone or in combination with 5-fluorouracil (5FU), which acts as a chemotherapeutic agent and radiosensitizer. Treatment efficiency of 18F-FLT combined or not with 5FU was evaluated by intratumoral (i.t.) infusion into subcutaneous HCT116 colorectal tumors implanted in nu/nu mice. The tumor uptake and kinetics of 18F-FLT were determined and compared to 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) by dynamic positron emission tomography (PET) imaging following i.t. injection. The therapeutic responses of 18F-FLT alone and with 5FU were evaluated and compared with 18F-FDG and external beam radiotherapy (EBRT). The level of prostaglandin E2 (PGE2) biosynthesis was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in order to determine the level of inflammation to healthy tissues surrounding the tumor, after i.t. injection of 18F-FLT, and compared to EBRT.ResultsWe found that i.t. administration of 18F-FLT offers (1) the highest tumor-to-muscle uptake ratio not only in the injected tumor, but also in distant tumors, suggesting potential for concurrent metastases treatment and (2) a sixfold gain in radiotherapeutic efficacy in the primary tumor relative to EBRT, which can be further enhanced with concurrent i.t. administration of the radiosensitizer 5FU. While EBRT stimulated PGE2 production in peritumoral tissues, no significant increase of PGE2 was measured in this area following i.t. administration of 18F-FLT.ConclusionConsidering the biochemical stability of 18F-FLT and the physical properties of localized 18F, this study shows that TRT via intratumoral infusion of 18F-FLT and 5FU could provide a new effective treatment option for solid tumors. Using this approach in a colorectal tumor model, the tumor and its metastases could be efficiently irradiated locally with much lower doses absorbed by healthy tissues than with i.t. administration of 18F-FDG or conventional EBRT.

Quantification of DNA damage in patients undergoing non-contrast and contrast enhanced whole body PET/CT investigations using comet assay and micronucleus assay

Objective: To quantify DNA damage in patients undergoing non-contrast and contrast-enhanced 18F-FDG PET/CT whole body positron emission tomography/computed tomography (WB PET/CT) investigations using comet assay technique and micronucleus assay, and to study the effect of other baseline parameters of patients on DNA damage.Methodology: Eighty-four patients referred for 18F-FDG PET/CT investigation were included in the study of which 44 patients underwent contrast-enhanced WB PET/CT and 40 patients underwent non-contrast WB PET/CT investigations. The investigations were performed on Discovery 690 PET/CT. For contrast-enhanced investigation, Omnipaque300 was injected intravenously based on the patient body weight. Absorbed dose resulting from the intravenous administration of 18F-FDG was estimated using the ICRP 106 dose coefficients. Radiation dose from the acquisition of CT scans was estimated using CT dose index and dose-length product. Blood samples were collected from the patients for DNA damage analysis. Comet assay and MN assay was used to assess the DNA damage. The Differences in the comet TM (Tail Moment) and MNBC % in both groups were calculated.Result: The radiation dose received by the study population during 18F-FDG WB PET/CT examination was 27.03 ± 2.33 mSv. Comet TM and percentage frequency of MNBC % was 65.22 ± 35.42 and 18.55 ± 10.14, respectively in the patients injected with contrast and 42.49 ± 28.52 and 13.76 ± 7.52 for non-contrast group. Significant increase in DNA damage was observed in the contrast group as compared to non-contrast group. Significant association was observed between patient weight, contrast volume and TM and MNBC%. Baseline parameters of the patients did not show significant correlation with TM and MNBC%.Conclusion: The patients undergoing contrast-enhanced WB PET/CT investigations have demonstrated higher DNA damage. The DNA damage was also observed to be more in heavier patients. The other baseline parameters of patients like age, sex, CBG, serum creatinine did not show any correlation with DNA damage.

Finger Radiation Doses Received By Different Nuclear Medicine Working Professions in Three PET/ CT Centers.

In the present study, we have investigated the finger radiation doses received by nuclear medicine staff involved in dispensing, administration of 18F-FDG and interacting with radioactive patients during imaging procedures in PET/ CT facility within three different diagnostic centers. Materials and methods: Using finger ring dosimeters delivered to physicists, technicians, and nurses, the readings were collected after one month of working. Each with his own assigned job task that varies according to the center’s policy. Results: Finger doses were found to be within the permissible limits. The mean prospective annual finger dose measurements, across the three centers show that the physicist group has the highest received prospective annual dose 440.01 mSv/year. The mean technician's prospective annual finger dosemeasurements, across the three centers, appeared to be the lowest scoring 94.83 mSv/year and nurses measured 115.8 mSv/year. Finally, there was no recorded significance for the studied categories across the three centers between their prospective annual finger dose measurements. The highest finger dose was recorded for the physicists who are likely exposed from the handling of the 18F-FDG multi-dose syringe, transferring the dose to the injection room and measuring the post-injection residual dose in the syringe. The nurse performed shorter part with ready-made individual radiopharmaceutical syringe and pre- intravenous time before and during administration. Also, the technicians spent the maximal time per study; however, they have the lowest finger dose because they are not exposed directly to handle the radioactive material.Conclusions: Finger doses are important indicator for the personal exposure especially for those workers who use their hands in dealing with radioactivematerials. The study revealed that the physicists are exposed higher than nurses and technologists in PET-CT facilities.

18f-Fludeoxyglucose and 11c-Methionine PET/CT Scans in Patients with Multiple Myeloma Following Autologous Stem-Cell Transplantation (auto-HSCT)

Introduction: Over the past years, possible use of PET/CT scan for diagnosis of multiple myeloma has been intensively studied; there is evidence that the use of 11C-methionine instead of 18F-fludeoxyglucose (18F-FDG) in multiple myeloma patients promotes the decrease in false negative PET/CT scan results. Comparative evaluation of the efficacy of detection of residual tumor lesions in MM patients following auto-HSCT using different radiopharmaceuticals for PET/CT scans is an important task.Goal of the study: To compare the results of tumor imaging using 18F-FDG and 11C-methionine PET/CT scan in MM patients following auto-HSCT.Materials and methods: Over the period from December 2016 to March 2018, 27 MM patients (8 males and 19 females) aged 32 to 64 years (median=57) were enrolled into a prospective study designed to evaluate efficacy of detection of tumor lesions using PET/CT scan technique. The disease stage according to the International Staging System (ISS) was I, II and III in 10, 7 and 10 patients, respectively. The onset of myeloma cast nephropathy was diagnosed in 4 (18%) patients, intraosseous plasmacytomas were found in 18 (67%) patients, extramedullary brain lesions was observed in 1 case. All patients received induction therapy with bortezomib; immunomodulatory drugs were used in 6 cases. Mobilization of CD34+ blood cells was carried out according to the regimen Cyclophosphamide 4 g/m2 + G-CSF. While using high-dose melphalan (200 mg/m2), a single (n=21) or tandem (n=6) auto-HSCT was conducted. On Day 100 after the initiation of auto-HSCT, PET/CT scan with two radiopharmaceuticals - 18F-FDG and 11C-methionine was performed. The obtained images were evaluated by visual inspection and semi-quantitative analysis. There were foci of increased accumulation of each agent (areas of hypermetabolism) not related to its physiological distribution. For each of the radiopharmaceuticals, the standardized uptake value (SUVmax) in the lesions was estimated automatically. The results of PET/CT and anti-tumor response achieved following auto-HSCT were compared according to the criteria developed by the International Myeloma Working Group. Statistical analysis was performed using Statistica 10 software. The quantitative values were expressed as the mean value ± standard deviation or the median value. Comparison of the respective measurements was carried out using the Student's t-test. To compare frequencies of data between independent groups, the Fisher's exact test or chi-square test were used.Results: Following auto-HSCT, 60% of patients demonstrated complete remission (CR). When using 18F-FDG, abnormal accumulation was observed in 37% (n=10) cases, PET-negative results were obtained in 63% (n=17) patients. Following administration of 11C-methionine, hypermetabolic foci were revealed in 67% (n=18) cases, lack of accumulation was observed in 33% (n=9) patients (Fig. 1). When using 11C-methionine, MM patients were found 1.8 times more likely to demonstrate abnormal accumulation of the radiopharmaceutical (p<0.02).Following administration of 18F-FDG, PET/CT scans of MM patients demonstrated 1 to 6 (mean value = 1±1.5) foci of abnormal fixation, while the use of 11C-methionine allowed revealing 1 to 12 (mean value=2.5±3.1) lesions. When using 11C-methionine, the number of lesions demonstrating abnormal accumulation of the radiopharmaceutical was 2.5 times that of 18F-FDG (p<0.05).Mean value of SUVmax for 18F-FDG was 1.02±1.6, while the mean value of SUVmax for 11C-methionine was 2.29±2.04. When using 11C-methionine, the values of SUVmax significantly exceeded the respective parameter associated with the use of 18F-FDG (p=0.02).Discussion: The results of our study have demonstrated a significant role of 11C-methionine for detection of tumor lesions in MM patients following auto-HSCT. The use of 11C-methionine PET/CT scan allows improving the accuracy of diagnosis of tumor lesions in MM patients following auto-HSCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Role of 18F-FDG PET/CT in evaluating molecular subtypes and clinicopathological features of primary breast cancer.

In this study, primary tumors' fluorine-18-fluorodeoxyglucose (F-FDG) uptake in luminal A, luminal B, triple-negative, and human epidermal growth factor receptor type-2 subtypes of breast cancer was evaluated. In addition, the relationship between the primary tumor maximum standardized uptake value (SUVmax) value and the presence of distant metastasis and axillary involvement was evaluated. Whole-body F-FDG PET/computed tomography (CT) imaging of 493 patients (mean age; 54.6±13.2 years) diagnosed with primary breast cancer were analyzed retrospectively. PET/CT imaging was obtained 60 min after the intravenous administration of F-FDG. F-FDG uptake of the lesions was assessed by calculating the SUVmax. Histopathological analyses were carried out on the basis of biopsy samples before PET/CT. For histopathological staging, the Scarff Bloom Richardson classification system was utilized, and patients were classified into luminal A, luminal B, triple-negative, and human epidermal growth factor receptor type-2 molecular subtypes. 82.9% of the patients had invasive ductal carcinoma, 5.8% had invasive lobular carcinoma, 4.2% had apocrine carcinoma, 3.8% had mucinous carcinoma, and 3.4% has mixed carcinoma. Although the highest mean SUVmax was calculated in apocrine tumors (12.4±7.2), the lowest mean SUVmax was calculated in lobular carcinoma (6.8±4.6), and a statistically significant difference was found between the histological groups (P<0.001). F-FDG uptake was reported to be significantly higher in the triple-negative subtype than the luminal types, and in the luminal B subtype than the luminal A subtype. A statistically significant relation was found between primary tumor SUVmax and distant nodal, organ metastasis (P=0.003 and <0.001, respectively). Increased primary tumor F-FDG uptake was associated with aggressive molecular subtypes in this study. The relationship of distant nodal and organ metastasis with primary tumor SUVmax showed that increased F-FDG uptake is important in terms of management of therapy and prognosis.

Dual-time point 18F-FDG PET/CT for the staging of oesophageal cancer: the best diagnostic performance by retention index for N-staging in non-calcified lymph nodes

The purpose of this study is to investigate the role of dual time point (DTP) 18F-FDG PET/CT in the staging of oesophageal cancer, especially in lymph node metastasis. A total of 35 patients with oesophageal squamous cell carcinoma who underwent surgical treatment without neoadjuvant chemotherapy were enrolled as a test set and another 19 patients were enrolled as a validation set. The DTP PET/CT scans were obtained in dual time points at 60 and 120min each, following the administration of 18F-FDG. Visual analysis was performed and semiquantitative analysis was performed using several PET parameters such as maximal standardized uptake values (SUVmax), peak SUV (SUVpeak) and retention indexes using SUVmax (RImax) and SUVpeak (RIpeak). Primary oesophageal lesions exhibited a significant difference for SUVmax at each time point scan (ANOVA, p < 0.001). For nodal staging, a total of 276 non-calcified nodal stations of the test set were evaluated. Sensitivity, specificity and accuracy of visual analysis were 32.0% (8 of 25), 96.8% (243 of 251) and 90.9% (251 of 276) in the test set. Using ROC analysis, RImax had the largest area under the curve (AUC) to detect metastatic lymphadenopathy at the optimal cut-off value of 6% (AUC 0.853, P < 0.001) in the test set (sensitivity, specificity and accuracy; 80.0% (20 of 25), 94.8% (238 of 251) and 93.5% (258 of 276)). In the validation set (179 non-calcified nodal stations), sensitivity, specificity and accuracy of RImax at the optimal cut-off of 6% were 71.4% (5 of 7), 99.4% (171 of 172) and 98.4% (176 of 179), whereas those of visual analysis were 14.3% (1 of 7), 98.8% (170 of 172) and 95.5% (171 of 179). The best diagnostic performance of nodal staging in patients with oesophageal cancer was achieved by application of RImax with a cut-off of more than 6% on DTP 18F-FDG PET/CT with the exclusion of calcified lymph nodes. Optimal clinical management in surgically-candidate oesophageal cancer patients could be achieved using the diagnostic flow on DTP 18F-FDG PET/CT.

Concurrent Respiratory Motion Correction of Abdominal PET and Dynamic Contrast-Enhanced-MRI Using a Compressed Sensing Approach.

We present an approach for concurrent reconstruction of respiratory motion-compensated abdominal dynamic contrast-enhanced (DCE)-MRI and PET data in an integrated PET/MR scanner. The MR and PET reconstructions share the same motion vector fields derived from radial MR data; the approach is robust to changes in respiratory pattern and does not increase the total acquisition time. Methods: PET and DCE-MRI data of 12 oncologic patients were simultaneously acquired for 6 min on an integrated PET/MR system after administration of 18F-FDG and gadoterate meglumine. Golden-angle radial MR data were continuously acquired simultaneously with PET data and sorted into multiple motion phases on the basis of a respiratory signal derived directly from the radial MR data. The resulting multidimensional dataset was reconstructed using a compressed sensing approach that exploits sparsity among respiratory phases. Motion vector fields obtained using the full 6-min (MC6-min) and only the last 1 min (MC1-min) of data were incorporated into the PET reconstruction to obtain motion-corrected PET images and in an MR iterative reconstruction algorithm to produce a series of motion-corrected DCE-MR images (moco_GRASP). The motion-correction methods (MC6-min and MC1-min) were evaluated by qualitative analysis of the MR images and quantitative analysis of SUVmax and SUVmean, contrast, signal-to-noise ratio (SNR), and lesion volume in the PET images. Results: Motion-corrected MC6-min PET images demonstrated 30%, 23%, 34%, and 18% increases in average SUVmax, SUVmean, contrast, and SNR and an average 40% reduction in lesion volume with respect to the non-motion-corrected PET images. The changes in these figures of merit were smaller but still substantial for the MC1-min protocol: 19%, 10%, 15%, and 9% increases in average SUVmax, SUVmean, contrast, and SNR; and a 28% reduction in lesion volume. Moco_GRASP images were deemed of acceptable or better diagnostic image quality with respect to conventional breath-hold Cartesian volumetric interpolated breath-hold examination acquisitions. Conclusion: We presented a method that allows the simultaneous acquisition of respiratory motion-corrected diagnostic quality DCE-MRI and quantitatively accurate PET data in an integrated PET/MR scanner with negligible prolongation in acquisition time compared with routine PET/DCE-MRI protocols.

Experimental study on the therapeutic effect and underlining mechanisms of positron in pancreatic cancer cells.

The purpose of this study was to assess the potential therapeutic effect of positrons emitted by 18F-2-Deoxy-2-Fluoro-D-Glucose (18F-FDG) on pancreatic cancer cells and elucidate its underlying mechanisms. Pancreatic cancer cells were incubated with different radioactive concentrations of 18F-FDG and evaluated for anti-cancer properties and underlining mechanisms. In addition, three groups of tumor-bearing mice were treated with different doses of 18F-FDG weekly, the tumor growth rate was calculated, and the mice were imaged by positron emission tomography (PET) with 18F-FDG before and after treatment. The presence of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stain and immunohistochemistry analysis. All treated groups exhibited positron-inhibited proliferation and positron-induced apoptosis compared with the control group in vitro. Further, we noted that higher treatment dose correlated with a better treatment response. In vivo, the high dose administration of 18F-FDG reduced tumor growth and prolonged the survival of treated mice compared with the control group with no change in the behavior or normal tissues of the mice. Immunohistochemical analysis and TUNEL stain showed more apoptotic cells than that in control group. The results demonstrated that positron radiation inhibited the proliferation and induced apoptosis of pancreatic cancer cells in vitro and in vivo, via an endogenous mitochondria-mediated signaling pathway.