Whole-body PET Scans Research Articles

S1935 Anorectal Melanoma: A Rare but Potentially Fatal Cause of Rectal Bleeding

Introduction: Rectal bleeding is a common complaint with many relatively benign causes including hemorrhoids, anal fissures, and colonic diverticula. However, there are more insidious causes of rectal bleeding that can potentially prove to be fatal without early intervention, including colon cancer. Here, we present one rare but potentially deadly cause of rectal bleeding. Case description/methods: A 63-year-old female presents with 1 month history of recurrent painless hematochezia. Prior to presentation, she had 3 episodes large volume bright red blood per rectum. Screening colonoscopy completed 3 years earlier was negative. On presentation the patient was hemodynamically stable, but severely anemic with hemoglobin of 6 g/dl. Digital rectal exam revealed a large anterior anal mass. Further evaluation with colonoscopy revealed a bleeding 2 cm submucosal mass in the anal canal, extending distal to the dentate line, which bled easily with pressure and fibrovascular in appearance. The mass was too friable to biopsy at the time of colonoscopy. She underwent trans-anal resection of the anal mass. Histopathology revealed nodular mucosal malignant melanoma, epithelioid type. Immunohistochemical studies were positive for SOX-10 and Melan A, and negative for cytokeratin AE, CD45, chromogranin, synaptophysin, BRAF. Whole-body PET scan revealed 1.1 cm perirectal lymph node involvement without evidence of distant metastasis. Follow up MRI revealed six suspicious meso-rectal lymph nodes. Eventually, the patient underwent abdominoperineal resection (APR). Histopathology following APR revealed 3 tumor deposits, with negative surgical margin, 7/16 lymph nodes involvement. Patient is following oncology for adjuvant chemotherapy. Discussion: Anorectal melanoma (ARM) is rare, having fewer than 700 cases reported in the literature. Patients with anorectal melanoma typically present with rectal bleeding, anorectal pain, and change in bowel habits. The gold standard for diagnosis is immunohistochemistry. Treatment strategies include surgery with or without immunotherapy. Unfortunately, recurrence and mortality rate are high, with a 5-year survival rate of less than 20% and a median survival of less than 2 years. In summary, ARM is a rare and aggressive variant of mucosal melanoma which is often associated with diagnosis at advanced stage, high metastatic potential, and high mortality. It is imperative that a high index of suspicion be maintained to mitigate the high burden of late diagnoses and advanced disease.Figure 1.: Figure 1A. 4.3 x 3.5 cm mass anterior to a large sigmoid diverticulum with Hounsfield units of 22-36 (red arrow). Hounsfield units of lipomas range from 30 to 70. Figure 1B. 4 cm pedunculated polyp 20 cm from the anal verge. Figure 1C. Microscopy depicting submucosal mass with mature white adipose tissue (red arrow).

Biodistribution of 18F-FES in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant (G1T48), a Novel Selective ER Degrader.

16α-18F-fluoro-17β-estradiol (18F-FES) is a PET tracer characterizing the expression of the estrogen receptor (ER). Because therapy can interfere with the kinetics and biodistribution of 18F-FES, the aim of this study was to describe the biodistribution of 18F-FES in patients with metastatic ER-positive (ER+) breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader. Methods: Eight patients underwent 18F-FES PET/CT imaging at baseline, 4-6 wk during treatment with rintodestrant (interim), and after treatment. After intravenous administration of 200 MBq (±10%) of 18F-FES, a 50-min dynamic PET/CT scan of the thorax was obtained, followed by a whole-body PET/CT scan 60 min after injection. Blood samples were drawn for measuring whole blood and plasma activity concentration and the parent fraction of 18F-FES. Volumes of interest were placed in the aorta ascendens and in healthy tissues on both dynamic and whole-body PET scans. SUVs and target-to-blood ratios (TBRs) were calculated. Areas under the curve (AUCs) of input functions and time-activity curves were calculated as a measure of uptake in different regions. Results:18F-FES concentration in whole blood (and plasma) significantly (P < 0.05) increased at interim with median AUCs of 96.6, 116.6, and 110.3 at baseline, interim, and after treatment, respectively. In ER-expressing tissues, that is, the uterus and the pituitary gland, both SUV and TBR showed high 18F-FES uptake at baseline, followed by a decrease in uptake at interim (uterus: SUV -50.6% and TBR -58.5%; pituitary gland: SUV -39.0% and TBR -48.3%), which tended to return to baseline values after treatment (uterus: SUV -21.5% and TBR -37.9%; pituitary gland: SUV -14.2% and TBR -26.0%, compared with baseline). In other healthy tissues, tracer uptake remained stable over the 3 time points. Conclusion: The biodistribution of 18F-FES is altered in blood and in ER-expressing healthy tissues during therapy with rintodestrant. This indicates that rintodestrant alters the kinetics of the tracer, possibly affecting interpretation and quantification of 18F-FES uptake. Of note, 6 d or more after treatment with rintodestrant ended, the biodistribution returned to baseline values, consistent with recovery of ER availability after washout of the drug.

Assessing the Functional Redundancy between P-gp and BCRP in Controlling the Brain Distribution and Biliary Excretion of Dual Substrates with PET Imaging in Mice.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are co-localized at the blood–brain barrier, where they display functional redundancy to restrict the brain distribution of dual P-gp/BCRP substrate drugs. We used positron emission tomography (PET) with the metabolically stable P-gp/BCRP substrates [11C]tariquidar, [11C]erlotinib, and [11C]elacridar to assess whether a similar functional redundancy as at the BBB exists in the liver, where both transporters mediate the biliary excretion of drugs. Wild-type, Abcb1a/b(−/−), Abcg2(−/−), and Abcb1a/b(−/−)Abcg2(−/−) mice underwent dynamic whole-body PET scans after i.v. injection of either [11C]tariquidar, [11C]erlotinib, or [11C]elacridar. Brain uptake of all three radiotracers was markedly higher in Abcb1a/b(−/−)Abcg2(−/−) mice than in wild-type mice, while only moderately changed in Abcb1a/b(−/−) and Abcg2(−/−) mice. The transfer of radioactivity from liver to excreted bile was significantly lower in Abcb1a/b(−/−)Abcg2(−/−) mice and almost unchanged in Abcb1a/b(−/−) and Abcg2(−/−) mice (with the exception of [11C]erlotinib, for which biliary excretion was also significantly reduced in Abcg2(−/−) mice). Our data provide evidence for redundancy between P-gp and BCRP in controlling both the brain distribution and biliary excretion of dual P-gp/BCRP substrates and highlight the utility of PET as an upcoming tool to assess the effect of transporters on drug disposition at a whole-body level.

First clinical assessment of [18F]MC225, a novel fluorine-18 labelled PET tracer for measuring functional P-glycoprotein at the blood-brain barrier.

5-(1-(2-[18F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen ([18F]MC225) is a selective substrate for P-glycoprotein (P-gp), possessing suitable properties for measuring overexpression of P-gp in the brain. This is the first-in-human study to examine safety, radiation dosimetry and P-gp function at the blood-brain barrier (BBB) of [18F]MC225 in healthy subjects. [18F]MC225 biodistribution and dosimetry were determined in 3 healthy male subjects, using serial 2h and intermittent 4 and 6h whole-body PET scans acquired after [18F]MC225 injection. Dynamic [18F]MC225 brain PET (90min) was obtained in 5 healthy male subjects. Arterial blood was sampled at various time intervals during scanning and the fraction of unchanged [18F]MC225 in plasma was determined. T1-weighted MRI was performed for anatomical coregistration. Total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1-TCM and 2-TCM, respectively). VT was also estimated using the Logan graphical method (Logan plot) (t* = 20min). Surrogate parameters without blood sampling (area-under the curve [AUC] of regional time-activity curves [TACs] and negative slope of calculated TACs) were compared with the VT values. No serious adverse events occurred throughout the study period. Although biodistribution implied hepatobiliary excretion, secretion of radioactivity from liver to small intestine through the gallbladder was very slow. Total renal excreted radioactivity recovered during 6h after injection was < 2%ID. Absorbed dose was the highest in the pancreas (mean ± SD, 203 ± 45μGy/MBq) followed by the liver (83 ± 11μGy/MBq). Mean effective dose with and without urination was 17 ± 1 μSv/MBq. [18F]MC225 readily entered the brain, distributing homogeneously in grey matter regions. 2-TCM provided lower Akaike information criterion scores than did 1-TCM. VT estimated by Logan plot was well correlated with that of 2-TCM (r2 > 0.9). AUCs of TACs were positively correlated with VT (2-TCM) values (r2: AUC0-60min = 0.61, AUC0-30min = 0.62, AUC30-60min = 0.59, p < 0.0001). Negative slope of SUV TACs was negatively correlated with VT (2-TCM) values (r2 = 0.53, p < 0.0001). This initial evaluation indicated that [18F]MC225 is a suitable and safe PET tracer for measuring P-gp function at the BBB.

Performance comparison of a dedicated total breast PET system with a clinical whole-body PET system: a simulation study

This paper presents a novel PET geometry for breast cancer imaging. The scanner consists of a ‘stadium’ (a rectangle with two semi-circles on opposite sides) shaped ring, along with anterior and posterior panels to provide high sensitivity and high spatial resolution for an imaging field-of-view (FOV) that include both breasts, mediastinum and axilla. We simulated this total-breast PET system using GATE and reconstructed the coincidence events using a GPU-based list-mode image reconstruction implementing maximum likelihood expectation-maximization (ML-EM) algorithm. The rear-panel is made up of a single layer of LSO crystals (3.2 × 3.2 × 20 mm3 each), while the ‘stadium’-shaped elongated ring and the anterior panel are made with dual-layered LSO crystals (1.6 × 1.6 × 6 mm3 each). The energy resolution and coincidence resolving time of all detectors are assumed to be 12% and 250 ps full-width-at-half-maximum, respectively. Various sized simulated lesions (4, 5, 6 mm) having 4:1, 5:1, and 6:1 lesion-to-background radioactivity concentration ratios, mimicking different biological uptakes, were strategically located throughout a volumetric torso phantom. We compared system sensitivity and lesion detectability of the dedicated total-breast PET system to a state-of-the-art clinical whole-body PET scanner. The mean sensitivity of the total-breast PET system is 3.21 times greater than that of a whole-body PET scanner in the breast regions. The total-breast PET system also provides better contrast-recovery coefficients for lesions of all sizes and lesion-to-background ratios in the breast when compared to a reference clinical whole-body PET scanner. Receiver operating characteristics (ROC) study shows the area under the ROC curve is 0.948 and 0.924 for the total-breast system and the whole-body PET scanner, respectively, in the detection of 4 mm diameter lesions with 4:1 lesion-to-background ratio. This study demonstrates our novel geometry can provide an imaging FOV larger than conventional PEM systems to simultaneously image both breasts, chest wall and axillae with significantly improved lesion detectability in the breasts when compared to a whole-body PET scanner.

Prediction of pathological complete response after neoadjuvant chemotherapy in breast cancer: comparison of diagnostic performances of dedicated breast PET, whole-body PET, and dynamic contrast-enhanced MRI.

To compare the diagnostic performance of ring-type dedicated breast PET (dbPET), whole-body PET (WBPET), and DCE-MRI for predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). This prospective study included 29 women with histologically proven breast cancer on needle biopsy between July 2016 and July 2019 (age: mean 55years; range 35-78). Patients underwent WBPET followed by ring-type dbPET and DCE-MRI pre- and post-NAC for preoperative evaluation. pCR was defined as an invasive tumor that disappeared in the breast. Standardized uptake values corrected for lean body mass (SULpeak) were calculated for dbPET and WBPET scans. Maximum tumor length was measured in DCE-MRI images. Reduction rates were calculated for quantitative evaluation. Two radiologists independently evaluated the qualitative findings. Reduction rates and qualitative findings were compared between the pCR (n = 7) and non-pCR (n = 22) groups for each modality. Differences in quantitative and qualitative data between the two groups were analyzed statistically. Significant differences were observed in the reduction rates of dbPET and DCE-MRI (P = 0.01 and 0.03, respectively) between the two groups. Univariate and multiple logistic regression analyses revealed that SULpeak reduction rates in WBPET and dbPET (P = 0.02 and P = 0.01, respectively) and in dbPET (odds ratio, 16.00; 95% CI 1.57-162.10; P = 0.01) were significant indicators associated with pCR, respectively. No between-group differences were observed in qualitative findings in the three modalities. SULpeak reduction rate of dbPET > 82% was an independent indicator associated with pCR after NAC in breast cancer.

Evaluation of Large-Area Silicon Photomultiplier Arrays for Positron Emission Tomography Systems

An individual readout of silicon photomultipliers (SiPMs) would enhance the performance of modern positron emission tomography (PET) systems. However, as it difficult to achieve in practice, a multiplexing readout of SiPM arrays could be performed instead. In this study, we characterized the performance of three PET detector modules utilizing three different SiPM models with active areas of 3 × 3, 4 × 4, and 6 × 6 mm2. Each SiPM array was coupled with a 4 × 4 LYSO crystal block. For SiPM multiplexing, we used a discretized positioning circuit to obtain position and energy information, and applied a first-order capacitive high-pass filter to enhance the time-of-flight measurement capability of the PET detector. The energy performance was similar among the three different SiPM arrays, with an energy resolution of 10%–11%. The best timing performance was achieved with the SiPM array with an active area of 6 × 6 mm2, which yielded a coincidence timing resolution (CTR) value of 401 ps FWHM when an analog high-pass filter was applied. We expect that, in combination with high-performance SiPM multiplexing techniques, the SiPM array with an active area of 6 × 6 mm2 can provide a cost-effective solution for developing a whole-body PET scanner.

Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide

PurposeTo assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier.ProceduresTen healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module.ResultsThe majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively.Conclusions[11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.

Biodistribution and radiation dosimetry of D-isomer of 4-borono-2-[18F]fluoro-phenylalanine: A comparative PET/CT study with L-isomer in healthy human volunteers

IntroductionL-isomer of 4-borono-2-18F-fluoro-phenylalanine (L-[18F]FBPA) was generally applied in clinic for boron neutron capture therapy (BNCT). With radiotracer validation, D-isomer of [18F]FBPA (D-[18F]FBPA) was found a higher tumor to normal brain tissue ratio (TBR) than its L-isomer on positron emission tomography (PET) in rat brain glioma. The present study was conducted as a first-in-human study to explore the biodistribution and radiation dosimetry of D-[18F]FBPA in healthy human volunteers, compared with L-[18F]FBPA. MethodsD-[18F]FBPA or L-[18F]FBPA was injected intravenously. Five whole-body PET scans were performed for each subject in the next 2 h. Organ time-activity curves were drawn by measuring SUVmean in volumes of interest. Absorbed dose coefficient of target organs and effective dose (ED) were estimated on OLINDA/EXM. ResultsTwo healthy volunteers (both males) and three healthy volunteers (2 males, 1 female) were intravenously injected with D-[18F]FBPA (5.5–7.2 MBq/kg) and L-[18F]FBPA (3.9–6.8 MBq/kg) respectively. Only limited accumulation of D-[18F]FBPA was observed in healthy human brain, pancreas, liver, spleen and skeleton. The ED was calculated to be 0.026 mSv/MBq. Urinary bladder wall received the highest dose of 0.28 mGy/MBq, followed by kidneys (0.06 mGy/MBq), and all the other organs received less than 0.03 mGy/MBq. For L-[18F]FBPA, higher uptake in brain, pancreas, liver, spleen and skeleton could be visualized, compared with D-[18F]FBPA. The ED of L-[18F]FBPA was 0.020 ± 0.001 mSv/MBq. Urinary bladder wall and kidneys still received the highest dose among organs but with lower values than those of D-[18F]FBPA. ConclusionsD-[18F]FBPA had lower activity in normal brain, liver, spleen, pancreas and skeleton, compared with its L-isomer. D-[18F]FBPA is safe from a radiological standpoint. Advances in knowledge and implications for patient careD-[18F]FBPA was safe from a radiological standpoint, and had lower activity in normal brain, liver, spleen, pancreas and skeleton than its L-isomer. This study ensures the safety and validity of D-[18F]FBPA for further clinical trials in patients with cancer.

Practical joint reconstruction of activity and attenuation with autonomous scaling for time-of-flight PET

Recent research has showed that attenuation images can be determined from emission data, jointly with activity images, up to a scaling constant when utilizing the time-of-flight (TOF) information. We aim to develop practical CT-less joint reconstruction for clinical TOF PET scanners to obtain quantitatively accurate activity and attenuation images. In this work, we present a joint reconstruction of activity and attenuation based on MLAA (maximum likelihood reconstruction of attenuation and activity) with autonomous scaling determination and joint TOF scatter estimation from TOF PET data. Our idea for scaling is to use a selected volume of interest (VOI) in a reconstructed attenuation image with known attenuation, e.g. a liver in patient imaging. First, we construct a unit attenuation medium which has a similar, though not necessarily the same, support to the imaged emission object. All detectable LORs intersecting the unit medium have an attenuation factor of e −1≈ 0.3679, i.e. the line integral of linear attenuation coefficients is one. The scaling factor can then be determined from the difference between the reconstructed attenuation image and the known attenuation within the selected VOI normalized by the unit attenuation medium. A four-step iterative joint reconstruction algorithm is developed. In each iteration, (1) first the activity is updated using TOF OSEM from TOF list-mode data; (2) then the attenuation image is updated using XMLTR—a extended MLTR from non-TOF LOR sinograms; (3) a scaling factor is determined based on the selected VOI and both activity and attenuation images are updated using the estimated scaling; and (4) scatter is estimated using TOF single scatter simulation with the jointly reconstructed activity and attenuation images. The performance of joint reconstruction is studied using simulated data from a generic whole-body clinical TOF PET scanner and a long axial FOV research PET scanner as well as 3D experimental data from the PennPET Explorer scanner. We show that the proposed joint reconstruction with proper autonomous scaling provides low bias results comparable to the reference reconstruction with known attenuation.

A validated Geant4 model of a whole-body PET scanner with four-layer DOI detectors

The purpose of this work is to develop a validated Geant4 simulation model of a whole-body prototype PET scanner constructed from the four-layer depth-of-interaction detectors developed at the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Japan. The simulation model emulates the behaviour of the unique depth of interaction sensing capability of the scanner without needing to directly simulate optical photon transport in the scintillator and photodetector modules. The model was validated by evaluating and comparing performance metrics from the NEMA NU 2-2012 protocol on both the simulated and physical scanner, including spatial resolution, sensitivity, scatter fraction, noise equivalent count rates and image quality. The results show that the average sensitivities of the scanner in the field-of-view were 5.9 cps kBq−1 and 6.0 cps kBq−1 for experiment and simulation, respectively. The average spatial resolutions measured for point sources placed at several radial offsets were 5.2± 0.7 mm and 5.0± 0.8 mm FWHM for experiment and simulation, respectively. The peak NECR was 22.9 kcps at 7.4 kBq ml−1 for the experiment, while the NECR obtained via simulation was 23.3 kcps at the same activity. The scatter fractions were 44% and 41.3% for the experiment and simulation, respectively. Contrast recovery estimates performed in different regions of a simulated image quality phantom matched the experimental results with an average error of -8.7% and +3.4% for hot and cold lesions, respectively. The results demonstrate that the developed Geant4 model reliably reproduces the key NEMA NU 2-2012 performance metrics evaluated on the prototype PET scanner. A simplified version of the model is included as an advanced example in Geant4 version 10.5.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.

245 ps-TOF brain-dedicated PET prototype with a hemispherical detector arrangement

Brain PET, which has led research in molecular imaging and diagnosis of brain cancer, epilepsy and neurodegenerative disorders, is being spotlighted again to promote earlier diagnosis of dementia with the advent of amyloid and tau tracers. To meet this demand, in this paper, we developed a brain-dedicated PET imaging device with a hemispherical detector arrangement, which provides comparable sensitivity with fewer detectors than conventional cylindrical geometries. The introduction of the time-of-flight (TOF) measurement capability was a key point for the development to get a gain in the image signal-to-noise ratio. Currently, whole-body PET scanners with around 200–400 ps coincidence resolving time (CRT) are commercially available. In order to obtain the same TOF gain which can be obtained with 400 ps CRT for a 30 cm diameter object, 267 ps CRT will be required for a 20 cm diameter object such as the human head. In this work, therefore, we aimed at developing a TOF brain-dedicated PET prototype with the hemisphere detector arrangement and the CRT faster than 267 ps. The detector was composed of a 12 × 12 lutetium fine silicate (LFS) array coupled with a 12 × 12 multi-pixel photon counter (MPPC) array. Each LFS crystal with a size of 4.14 × 4.14 × 10 mm3 was individually coupled to a separate MPPC. Singles list-mode data from each detector were stored, and coincidences were identified using a coincidence-detection software algorithm. The CRT of 245 ps was finally achieved as the system average after a fine timing correction. For image reconstruction, we implemented the list-mode TOF-OSEM. For a small rod phantom, rods of 3 mm diameter were clearly separated. Also, images of the 3D Hoffman brain phantom, which demonstrated clear contrast between gray and white matter, supported the effect of TOF information.

Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J

The ability to quantify synaptic density in vivo in human adults and adolescents is of vital importance to understanding neuropsychiatric disorders. Here, we performed whole-body scans to determine organ radiation dosimetry of 11C-UCB-J in humans.MethodsDynamic whole-body PET scans were performed in four healthy adults after injection of 11C-UCB-J. Regions of interest (ROIs) were drawn manually for the brain, heart, stomach, kidneys, liver, pancreas, spleen, gallbladder, lungs, urinary bladder, and intestines. ROIs were applied to dynamic images to generate time-activity curves (TACs). Decay correction was removed from TACs, and the area under the curve (AUC) for each ROI was calculated. AUCs were then normalized by injected activity and organ volumes to produce radioligand residence times for each organ. These times were then used as input into the OLINDA/EXM 1.0 software to determine the total radiation dose in each organ and the effective dose for these OLINDA models: 55-kg female, 70-kg male, and 15-year-old adolescent.ResultsVisual evaluation detected high uptake in the liver, brain, gallbladder, gastrointestinal tract, and urinary bladder. The dose-limiting organ was the urinary bladder for adult males (0.0224 mSv/MBq) and liver for adult females (0.0248 mSv/MBq) with single-study dose limits of 2239 MBq and 2017 MBq 11C-UCB-J, respectively. For adolescents, the large intestine was the dose-limiting organ (0.0266 mSv/MBq) with a single-study dose limit of 188 MBq.Conclusions11C-UCB-J dosimetry in adults is consistent with those for many carbon-11-labeled ligands. Overall, 11C-UCB-J can be used safely in adolescents, as in adults, to measure synaptic density in various neuropsychiatric and other relevant disorders.

18F]AlF-NOTA-octreotide PET imaging: biodistribution, dosimetry and first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour patients.

The widespread use of gallium-68-labelled somatostatin analogue (SSA) PET, the current standard for somatostatin receptor (SSTR) imaging, is limited by practical and economic challenges that could be overcome by a fluorine-18-labelled alternative, such as the recently introduced [18F]AlF-NOTA-octreotide ([18F]AlF-OC). This prospective trial aimed to evaluate safety, dosimetry, biodistribution, pharmacokinetics and lesion targeting of [18F]AlF-OC and perform the first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour (NET) patients. Six healthy volunteers and six NET patients with a previous clinical [68Ga]Ga-DOTATATE PET were injected with an IV bolus of 4MBq/kg [18F]AlF-OC. Healthy volunteers underwent serial whole-body PET scans from time of tracer injection up to 90min post-injection, with an additional PET/CT at 150 and 300min post-injection. In patients, a 45-min dynamic PET was acquired and three whole-body PET scans at 60, 90 and 180min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake (SUVmean) and tumour lesion uptake (SUVmax and tumour-to-background ratio (TBR)) were measured. A lesion-by-lesion analysis was performed and the detection ratio (DR), defined as the fraction of detected lesions was determined for each tracer. [18F]AlF-OC administration was safe and well tolerated. The highest dose was received by the spleen (0.159 ± 0.062mGy/MBq), followed by the urinary bladder wall (0.135 ± 0.046mGy/mBq) and the kidneys (0.070 ± 0.018mGy/MBq), in accordance with the expected SSTR-specific uptake in the spleen and renal excretion of the tracer. The effective dose was 22.4 ± 4.4μSv/MBq. The physiologic uptake pattern of [18F]AlF-OC was comparable to [68Ga]Ga-DOTATATE. Mean tumour SUVmax was lower for [18F]AlF-OC (12.3 ± 6.5 at 2h post-injection vs. 18.3 ± 9.5; p = 0.03). However, no significant differences were found in TBR (9.8 ± 6.7 at 2h post-injection vs. 13.6 ± 11.8; p = 0.35). DR was high and comparable for both tracers (86.0% for [68Ga]Ga-DOTATATE vs. 90.1% for [18F]AlF-OC at 2h post-injection; p = 0.68). [18F]AlF-OC shows favourable kinetic and imaging characteristics in patients that warrant further head-to-head comparison to validate [18F]AlF-OC as a fluorine-18-labelled alternative for gallium-68-labelled SSA clinical PET. Clinicaltrials.gov : NCT03883776, EudraCT: 2018-002827-40.

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance

BackgroundProstate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostate-specific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4–5 mm).ResultsThe main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET.ConclusionsWe have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organ-dedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.

124I-MIBG PET/CT to Monitor Metastatic Disease in Children with Relapsed Neuroblastoma.

The metaiodobenzylguanidine (MIBG) scan is one of the most sensitive noninvasive lesion detection modalities for neuroblastoma. Unlike 123I-MIBG, 124I-MIBG allows high-resolution PET. We evaluated 124I-MIBG PET/CT for its diagnostic performance as directly compared with paired 123I-MIBG scans. Methods: Before 131I-MIBG therapy, standard 123I-MIBG imaging (5.2 MBq/kg) was performed on 7 patients, including whole-body (anterior-posterior) planar imaging, focused-field-of-view SPECT/CT, and whole-body 124I-MIBG PET/CT (1.05 MBq/kg). After therapy, 2 of 7 patients also completed 124I-MIBG PET/CT as well as paired 123I-MIBG planar imaging and SPECT/CT. One patient underwent 124I-MIBG PET/CT only after therapy. We evaluated all 8 patients who showed at least 1 123I-MIBG-positive lesion with a total of 10 scans. In 8 pairs, 123I-MIBG and 124I-MIBG were performed within 1 mo of each other. The locations of identified lesions, the number of total lesions, and the curie scores were recorded for the 123I-MIBG and 124I-MIBG scans. Finally, for 5 patients who completed at least 3 PET/CT scans after administration of 124I-MIBG, we estimated the effective dose of 124I-MIBG. Results:123I-MIBG whole-body planar scans, focused-field-of-view SPECT/CT scans, and whole-body 124I-MIBG PET scans found 25, 32, and 87 total lesions, respectively. There was a statistically significant difference in lesion detection for 124I-MIBG PET/CT versus 123I-MIBG planar imaging (P < 0.0001) and 123I-MIBG SPECT/CT (P < 0.0001). The curie scores were also higher for 124I-MIBG PET/CT than for 123I-MIBG planar imaging and SPECT/CT in 6 of 10 patients. 124I-MIBG PET/CT demonstrated better detection of lesions throughout the body, including the chest, spine, head and neck, and extremities. The effective dose estimated for patient-specific 124I-MIBG was approximately 10 times that of 123I-MIBG; however, given that we administered a very low activity of 124I-MIBG (1.05 MBq/kg), the effective dose was only approximately twice that of 123I-MIBG despite the large difference in half-lives (100 vs. 13.2 h). Conclusion: The first-in-humans use of low-dose 124I-MIBG PET for monitoring disease burden demonstrated tumor detection capability superior to that of 123I-MIBG planar imaging and SPECT/CT.

Experimental investigation of the characteristics of radioactive beams for heavy ion therapy.

This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired postirradiation using an in-beam whole-body positron emission tomography scanner for range verification quality assurance. The energy deposited by monoenergetic beams of C at 350MeV/u, O at 250MeV/u, C at 350MeV/u, and O at 430MeV/u was measured using a cruciform transmission ionization chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose-mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon-on-insulator mushroom microdosimeter. Using the modified microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the postirradiation distributions of positron annihilations resulting from the decay of positron-emitting nuclei were measured for each beam in a gelatin phantom using the in-beam whole-body positron emission tomography scanner at HIMAC. The depth of maximum positron-annihilation density was compared with the depth of maximum dose deposition and the signal-to-background ratios were calculated and compared for images acquired over 5 and 20min postirradiation of the phantom. In the entrance region, the was 1.2±0.1 for both C and C beams, while for O and O it was 1.4±0.1 and 1.3±0.1, respectively. At the Bragg peak, the was 2.7±0.4 for C and 2.9±0.4 for C, while for O and O it was 2.7±0.4 and 2.8±0.4, respectively. In the tail region, could only be evaluated for carbon; the was 1.6±0.2 and 1.5±0.1 for C and C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal-to-background ratios compared to those obtained from targets irradiated by nonradioactive ion beams, with 5-fold and 11-fold increases in the ratios calculated for the O and C images compared with the values obtained for O and C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4±0.8mm for C, compared to -5.6±0.8mm for C and 0.9±0.8mm for O vs -6.6±0.8mm for O. The values for C and O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, C and O beams produce much better quality images for range verification compared with C and O, in particular with regard to estimating the location of the Bragg peak.

Simulation of novel scintillator crystals for brain PET

In the last decade, different positron emission tomography (PET) crystals have been proposed for brain PET detectors. Brain PET cameras with restricted field of view to a smaller size to cover the brain can both exhibit significantly higher performance and lower the cost when compared to conventional whole-body PET scanners. The existing designs based on scintillation crystals employ the most commonly known materials such as lutetium oxyorthosilicate and bismuth germanate. This is due to their relatively good parameters such as high light yield and density. The main drawback of using scintillation crystals is that they have a modest energy resolution. In this study, a brain PET scanner was designed and simulated using a Geant4 Application for Tomographic Emission (GATE) toolkit. The performances of five crystals, namely strontium hafnate, gadolinium aluminium gallium garnet, gadolinium yttrium gallium aluminium garnet, gadolinium lutetium gallium aluminium garnet, and lutetium oxyorthosilicate for comparison, were evaluated in terms of sensitivity, spatial resolution, and count rate. The performance evaluation results showed that among the suggested scintillators, strontium hafnate can be considered as a promising alternative detector for high performance brain PET systems.

Physiological fluorodeoxyglucose uptake of spinal cord in adults

Physiological fluorodeoxyglucose (FDG) uptake of spinal cord needs to be correctly recognized during evaluation of whole-body PET scans, especially for oncological cases. Our aim was to analyze physiological cord FDG uptake and its relation to gender, age, body weight, environmental temperature and time to imaging. PET scans of 254 patients in a single year, one patient for every working day were retrospectively selected. Temperature data were obtained from meteorology recordings. Maximum standard uptake value (SUVmax) of spinal cord at cervical and lower thoracic levels were noted. Spinal canal at L5 level, cerebellum and liver were used for normalization. Correlations with age, body weight, time to imaging and environmental temperature were analyzed. Cervical SUV was higher than thoracic SUV (2.5-2.3). Cervical and lower thoracic SUV's were strongly correlated, highest when corrected with L5 level vertebral canal and liver (corr coeff 0.84 and 0.75) and lowest with cerebellum (corr coeff 0.4). Cervical spinal cord FDG uptake was higher for females than males (2.6 to 2.4). Temperature and age did not change spinal cord uptake. There were weak positive correlations with body weight (corr coeff 0.16 and 0.28, cervical and thoracic). There was weak negative correlation of cervical uptake with time to imaging (corr coeff -0.17). Spinal cord FDG uptake at cervical and lower thoracic levels are strongly correlated. Females have slightly higher cervical SUV. Age and temperature does not change spinal cord FDG uptake in adults. Cord SUV's slightly increased with body weight.