Annals of Nuclear Medicine (v.28, #6)

Altered biodistribution of FDG in patients with type-2 diabetes mellitus by Mehmet A. Ozguven; Alper O. Karacalioglu; Semra Ince; Mustafa O. Emer (505-511).
Positron emission tomography–computed tomography (PET–CT) imaging of patients with diabetes can be problematic because elevated glucose levels may cause competitive inhibition of [F-18]-2-deoxy-2-fluoro-d-glucose (FDG) uptake in different tissues. Therefore, the aim of the study was to evaluate the biodistribution of FDG in patients with type-2 diabetes mellitus.Two hundred forty patients were retrospectively enrolled to the study. Study population was divided into three subgroups, named as the normal (group 1), the insulin (group 2) and the oral anti-diabetic (group 3). Unenhanced low-dose CT and PET emission data were acquired from the mid-thigh to the vertex of the skull. FDG uptakes in different organs were evaluated qualitatively or semi-quantitatively.In the diabetic groups, diffuse FDG uptake of the colon was increased (p > 0.001) but segmental FDG uptake was decreased (p > 0.001). Intestinal FDG uptake was detected in 20 % of the study population and only 3 % of these uptakes were in diffuse pattern. Segmental FDG uptake in the bowel was increased significantly in the groups of patients with diabetes (p = 0.002). Maximum standardized uptake values of the liver in the groups 1, 2, and 3 were 2.66 ± 0.6, 3.25 ± 0.9 and 3.16 ± 0.8, respectively, and the difference between the groups was not statistically significant (p = 0.083). Cardiac FDG uptake was decreased significantly in the groups of patients with diabetes (p < 0.001).According to our results, whole body biodistribution of FDG uptake seems to be changed in patients with type-2 diabetes who were using insulin or oral antidiabetic drugs. Although the use of oral antidiabetic drugs was known to change the biodistribution of FDG, insulin use also seems to change FDG uptake in different organs of diabetic patients.
Keywords: PET–CT; Type-2 diabetes mellitus; FDG uptake

Effect of surrounding materials on iterative reconstruction-based line-source response function, and annihilations outside the source assessed by a small animal PET scanner by Yoshiharu Miyazaki; Masato Kobayashi; Ryoko Komatsu; Akiko Hayashi; Shoko Yonezawa; Keiichi Kawai; Masamichi Matsudaira; Jun Shiozaki; Ichiro Matsunari (512-522).
The aims of this study were (1) to evaluate the effect of surrounding materials on the iterative reconstruction-based line-source response function (IR-RF) of 18F, 11C, 13N, and 15O using a preclinical PET system, and (2) to determine whether and how annihilation outside the source can be visualized experimentally.We performed all the measurements using the LabPET-8 PET/CT subsystem built-in the Triumph II platform (TriFoil Imaging, Inc., Northridge, CA, USA). IR-RF was measured for 18F, 11C, 13N, and 15O, and was expressed as full-width at half-maximum (FWHM) and full-width at tenth maximum (FWTM) using a glass capillary phantom mounted in materials of various densities, which were chosen to cover the wide range of real tissues. To determine whether and how annihilation outside the source can be visualized, we designed a concentric ring paper phantom, which consisted of a source at the center with 4 ring-like paper layers.When the radionuclides were placed in air (material density 0 g/cm3), IR-RFs were similar among the radionuclides tested. As the surrounding material density increased, IR-RFs for higher energy-emitting radionuclides (11C, 13N, and 15O) became worse, whereas those of 18F remained relatively constant over the range of surrounding material densities (0–2.17 g/cm3). Both FWHM and FWTM values were closely correlated with mean energy of radionuclides at middle to high material densities (material density 0.94–2.17 g/cm3). The FWTM/FWHM ratio of high energy-emitting radionuclides such as 15O increased as a function of material density, which was followed by subsequent decrease at high material densities (1.2–2.17 g/cm3). Using a concentric ring paper phantom, annihilations outside the source were visible and measurable. The innermost layer was visible with all radionuclides, whereas the outer layers only with high energy positron emitters.The results indicate that surrounding material affects IR-RF particularly for high energy positron emitters. Furthermore, annihilation outside the radio-active source can be visualized with some circumstances such as those seen with a concentric ring paper phantom.
Keywords: Iterative reconstruction-based spatial resolution; Positron range; Surrounding materials; PET; Annihilation

Evaluating the possible role of 68Ga-citrate PET/CT in the characterization of indeterminate lung lesions by Mariza Vorster; Alex Maes; Aldrich Jacobs; Sidney Malefahlo; Hans Pottel; Christophe Van de Wiele; Machaba Mike Sathekge (523-530).
We sought to determine whether PET/CT imaging with 68Ga-citrate could be of value in distinguishing benign from malignant lung pathology in a setting with a high prevalence of granulomatous diseases. Thirty-six consecutive patients with indeterminate lung lesions prospectively underwent dual time point (60 and 120 min) 68Ga-citrate PET/CT study prior to lung biopsy. Qualitative and semi-quantitative measures of tracer uptake in the lung lesions (SUVmax) were compared to the histopathology in order to establish an imaging pattern to distinguish benign from malignant lesions.Fourteen patients (38.9 %) were diagnosed with a malignant lesion, 12 (33.3 %) with tuberculosis (TB), and 10 participants (27.8 %) with other benign lung lesions. At 60-min post-injection, patients who were diagnosed with a malignant lesion (n = 14) demonstrated a mean SUVmax of 3.36 ± 1.14, with a median value of 3.04 (min = 1.56, max = 4.65).Those with TB (n = 12) demonstrated a SUVmax of 3.99 ± 2.28, and a median value of 3.71 (pct25 = 2.19, pct75 = 4.95). In patients with other benign lesions (n = 10), the following values were observed: a SUVmax of 2.70 ± 1.31, a median value of 2.50 (pct25 = 1.76, pct75 = 3.59). The mean values of these three types of pathology were not statistically significant (p = 0.1919), and therefore the SUVmax could not be used to accurately distinguish between these lesions using both early and delayed imaging.This study, as the first 68Ga-citrate PET/CT in humans for the in vivo imaging of lung pathology, demonstrated its potential for the detection of both malignancy and TB. However, 68Ga-citrate seemed incapable of providing a clear distinction between malignant and benign lung lesions in a setting with a high prevalence of granulomatous diseases such as TB.
Keywords: 68Ga-citrate; PET; Lung lesions

To demonstrate the safety of outpatient 7.8 GBq 177Lu-DOTA-tyr3-octreotate radiopeptide therapy of neuroendocrine tumors by measurement of radiation exposures of hospital personnel, carers and members of the public.Seventy-six patients with progressive, metastatic neuroendocrine tumors each received four cycles of prescribed activity of 7.8 GBq 177Lu-octreotate at 8-week intervals, as an outpatient procedure. Cohorts comprising four patients were treated in one room, each patient remaining in hospital until radiation exposure from them was below the release limit of 25 μSv h−1 at 1 m. On occasion, a single patient was treated in a single room. Radiation exposures of hospital staff and patient carers were monitored by personal dosimeter, and nearby areas monitored with a survey meter.Mean whole-body radiation exposures per therapy day ranged from 8 μSv (physicist) to 33 μSv (nurse), with exposures to personnel, carers and members of the public well within the limits recommended by the International Commission on Radiological Protection. Patients excreted a mean of 46 % of the total administered activity of 177Lu-octreotate within 4 h of therapy.Lutetium-177-octreotate radiopeptide therapy of neuroendocrine tumors can be safely performed as an outpatient treatment.
Keywords: Radiopeptide therapy; Radiation exposure; 177Lu-DOTA-tyr3-octreotate; Outpatient radionuclide therapy

To determine if metal artefact reduction (MAR) combined with a priori knowledge of prosthesis material composition can be applied to obtain CT-based attenuation maps with sufficient accuracy for quantitative assessment of 18F-fluorodeoxyglucose uptake in lesions near metallic prostheses.A custom hip prosthesis phantom with a lesion-sized cavity filled with 0.2 ml 18F-FDG solution having an activity of 3.367 MBq adjacent to a prosthesis bore was imaged twice with a chrome–cobalt steel hip prosthesis and a plastic replica, respectively. Scanning was performed on a clinical hybrid PET/CT system equipped with an additional external 137Cs transmission source. PET emission images were reconstructed from both phantom configurations with CT-based attenuation correction (CTAC) and with CT-based attenuation correction using MAR (MARCTAC). To compare results with the attenuation-correction method extant prior to the advent of PET/CT, we also carried out attenuation correction with 137Cs transmission-based attenuation correction (TXAC). CTAC and MARCTAC images were scaled to attenuation coefficients at 511 keV using a trilinear function that mapped the highest CT values to the prosthesis alloy attenuation coefficient. Accuracy and spatial distribution of the lesion activity was compared between the three reconstruction schemes.Compared to the reference activity of 3.37 MBq, the estimated activity quantified from the PET image corrected by TXAC was 3.41 MBq. The activity estimated from PET images corrected by MARCTAC was similar in accuracy at 3.32 MBq. CTAC corrected PET images resulted in nearly 40 % overestimation of lesion activity at 4.70 MBq. Comparison of PET images obtained with the plastic and metal prostheses in place showed that CTAC resulted in a marked distortion of the 18F-FDG distribution within the lesion, whereas application of MARCTAC and TXAC resulted in lesion distributions similar to those observed with the plastic replica.MAR combined with a trilinear CT number mapping for PET attenuation correction resulted in estimates of lesion activity comparable in accuracy to that obtained with 137Cs transmission-based attenuation correction, and far superior to estimates made without attenuation correction or with a standard CT attenuation map. The ability to use CT images for attenuation correction is a potentially important development because it obviates the need for a 137Cs transmission source, which entails extra scan time, logistical complexity and expense.
Keywords: PET/CT; Attenuation correction; Metal artefacts; Metal artefact reduction; Phantoms

Application of a medium-energy collimator for I-131 imaging after ablation treatment of differentiated thyroid cancer by Masato Kobayashi; Hiroshi Wakabayashi; Daiki Kayano; Takahiro Konishi; Hironori Kojima; Hiroto Yoneyama; Koichi Okuda; Hiroyuki Tsushima; Masahisa Onoguchi; Keiichi Kawai; Seigo Kinuya (551-558).
High-energy (HE) collimators are usually applied for I-131 imaging after ablation treatment of differentiated thyroid cancer (DTC). However, purchase of HE collimators has been avoided in many nuclear medicine departments because the HE collimators are more expensive than other collimators. In this study, we compared the I-131 imaging using HE- and medium-energy (ME) collimators, which is more versatile than HE collimators.To simulate DTC patients with extra-thyroid beds, a phantom of acrylic containers containing I-131 was used. To simulate patients with thyroid beds, four phantoms representing extra-thyroid beds were arranged around the phantom representing normal thyroid tissues. Patients administered 1.11 or 3.70 GBq NaI-131 were also evaluated. Whole-body imaging and SPECT imaging of the phantoms and patients performed using HE-general-purpose (HEGP) and ME-low-penetration (MELP) collimators, and full-width at half maximum (FWHM) and percent coefficient of variation (%CV) were measured.In the extra-thyroid beds, FWHM and %CV with MELP were negligibly different from those with HEGP in whole-body imaging. Although FWHM with MELP was a little different from that with HEGP in SPECT imaging, %CV with MELP was significantly higher than that with HEGP. In the thyroid beds, only an extra-thyroid bed including higher radioactivity was identified in whole-body imaging with both collimators. Although SPECT images with MELP could not clarify extra-thyroid beds with low radioactivity, HEGP could identify them. In patients, although some whole-body images with MELP could not detect extra-thyroid beds, whole-body imaging with HEGP and SPECT imaging with both collimators could detect them.Although HEGP is the best collimator for I-131 imaging, MELP is applicable for not only whole-body imaging but also SPECT imaging.
Keywords: NaI-131; Ablation; Differentiated thyroid cancer; Medium-energy collimator; High-energy collimator

Derivation of attenuation map for attenuation correction of PET data in the presence of nanoparticulate contrast agents using spectral CT imaging by Hossein Ghadiri; Mohammad Bagher Shiran; Hamid Soltanian-Zadeh; Arman Rahmim; Habib Zaidi; Mohammad Reza Ay (559-570).
Uptake value in quantitative PET imaging is biased due to the presence of CT contrast agents when using CT-based attenuation correction. Our aim was to examine spectral CT imaging to suppress inaccuracy of 511 keV attenuation map in the presence of multiple nanoparticulate contrast agents.Using a simulation study we examined an image-based K-edge ratio method, in which two images acquired from energy windows located above and below the K-edge energy are divided by one another, to identify the exact location of all contrast agents. Multiple computerized phantom studies were conducted using a variety of NP contrast agents with different concentrations. The performance of the proposed methodology was compared to conventional single-kVp and dual-kVp methods using wide range of contrast agents with varying concentrations.The results demonstrate that both single-kVp and dual-kVp energy mapping approaches produce inaccurate attenuation maps at 511 keV in the presence of multiple simultaneous contrast agents. In contrast, the proposed method is capable of handling multiple simultaneous contrast agents, thus allowing suppression of 511 keV attenuation map inaccuracy.Attenuation map produced by spectral CT clearly outperforms conventional single-kVp and dual-kVp approaches in the generation of accurate attenuation maps in the presence of multiple contrast agents.
Keywords: PET/CT; Nanoparticulate contrast agents; K-edge imaging; Multi-energy spectral CT

Higher reliability of 18F-FDG target background ratio compared to standardized uptake value in vulnerable carotid plaque detection: a pilot study by Artor Niccoli Asabella; Marco M. Ciccone; Francesca Cortese; Pietro Scicchitano; Michele Gesualdo; Annapaola Zito; Alessandra Di Palo; Domenico Angiletta; Guido Regina; Andrea Marzullo; Giuseppe Rubini (571-579).
To evaluate the role of [18F]-fluorodeoxyglucose positron emission tomography/computer tomography [18F-FDG PET/CT] comparing target background ratio (TBR) and standardized uptake value (SUV) with the histopathological inflammatory status of the carotid plaques.Vulnerable carotid plaques are the primary cause of acute cerebrovascular events. 18F-FDG PET/CT represents a morpho-functional technique able to identify the highly inflamed and most vulnerable carotid plaques. Several literature studies experimented this new method to identify vascular inflammation, but few have effectively compared PET/CT results with plaque histological data and no studies had directly compared TBR to SUV.Thirty-two consecutive patients (20 men and 12 women, mean age 74 ± 8 years) undergoing carotid endarterectomy were enrolled and studied with carotid 18F-FDG PET/CT. Maximum and mean SUV and TBR were used to quantify 18F-FDG uptake while surgical specimens were analyzed by optical microscopy to identify inflamed carotid plaques, with evaluation of macrophages infiltration by mean of immunohistochemistry. On the basis of the presence of inflammation at the histological analysis, we divided population in two groups: group A (n = 12) patients with inflamed carotid plaques and group B (n = 20) patients with non-inflamed ones, then crossed and evaluated the histological data with 18F-FDG PET/CT findings.SUV max and SUV mean values resulted higher in group A (respectively, 2.14 ± 0.77 and 1.99 ± 0.68) than in group B (respectively, 1.79 ± 0.37 and 1.64 ± 0.34) without reaching a statistical significance (p = ns). TBR max and TBR mean values resulted higher in group A (respectively, 1.42 ± 0.32 and 1.34 ± 0.26) than in group B (respectively, 1.16 ± 0.19 and 1.03 ± 0.20) with a statistically significant differences between the two groups and carotid inflammation (respectively, p < 0.01 and p < 0.001).TBR (max and mean values) is a more reliable parameter than SUV in identifying inflamed plaques. Although limited by the small population analyzed, our results suggest the important role of 18F-FDG PET/CT, using TBR, in identification of high-risk carotid atherosclerotic plaques.
Keywords: PET/CT; Vulnerable carotid plaques; Histology

Cardiac motion is a challenging cause of image artefacts in myocardial perfusion SPECT. A wide range of motion correction methods have been developed over the years, and so far automatic algorithms based on the reconstruction—reprojection principle have proved to be the most effective. However, these methods have not been fully optimised in terms of their free parameters and implementational details.Two slightly different implementations of reconstruction—reprojection-based motion correction techniques were optimised for effective, good-quality motion correction and then compared with each other. The first of these methods (Method 1) was the traditional reconstruction-reprojection motion correction algorithm, where the motion correction is done in projection space, whereas the second algorithm (Method 2) performed motion correction in reconstruction space. The parameters that were optimised include the type of cost function (squared difference, normalised cross-correlation and mutual information) that was used to compare measured and reprojected projections, and the number of iterations needed. The methods were tested with motion-corrupt projection datasets, which were generated by adding three different types of motion (lateral shift, vertical shift and vertical creep) to motion-free cardiac perfusion SPECT studies.Method 2 performed slightly better overall than Method 1, but the difference between the two implementations was small. The execution time for Method 2 was much longer than for Method 1, which limits its clinical usefulness. The mutual information cost function gave clearly the best results for all three motion sets for both correction methods. Three iterations were sufficient for a good quality correction using Method 1.The traditional reconstruction—reprojection-based method with three update iterations and mutual information cost function is a good option for motion correction in clinical myocardial perfusion SPECT.
Keywords: Reconstruction—reprojection; Motion correction; Cardiac SPECT

We developed a bubble point test kit and investigated the bubble point test of a 0.22-μm membrane filter used for the sterilizing filtration of [18F]FDG, [11C]MET and [11C]PIB. The bubble point test of the Millex-GS vented filter was often difficult due to air leakage from the vented portion of this filter. Therefore, to close the vented portion of this filter simply and reliably, we investigated the use of various materials.The bubble point test of the Millex-GS vented filter was performed by closing the vented portion of this filter with various materials, such as vinyl tape, plastic paraffin film (parafilm), urethane elastomer adhesive mat and polyethylene foam cushion tape. Gradually, the plunger inside a syringe filled with air was pushed down to increase the pressure on the pressure gauge and the bubble point test kit. Simultaneously, the pressure when a continuous stream of air bubbles that appeared out of the 0.22-μm membrane filter was measured as the product-wetted bubble point value. Then, the plunger inside a syringe filled with 10 mL of water was pushed down to wash the 0.22-μm membrane filter. As in the case in the above-mentioned method of measuring the product-wetted bubble point, the water-wetted bubble point value was measured.The use of the polyethylene foam cushion tape and a double clip could easily and reliably prevent air leakage from the vented portion of the Millex-GS vented filter. In the bubble point test of [18F]FDG, [11C]MET and [11C]PIB, the product-wetted bubble point values were 382.7 ± 6.9 kPa, 385.4 ± 6.2 kPa and 351.6 ± 7.6 kPa, respectively. The bubble point ratio was used to determine the minimum product-wetted bubble point value. All results of the product-wetted bubble point test were beyond the minimum product-wetted bubble point value (334.4 kPa ([18F]FDG), 334.4 kPa ([11C]MET) and 310.3 kPa ([11C]PIB)). Then, the water-wetted bubble point values were 396.5 ± 8.3 kPa, 395.8 ± 8.3 kPa and 390.3 ± 7.6 kPa, respectively. All results of the water-wetted bubble point test were beyond the filter manufacturer’s minimum bubble point specification (344.8 kPa).The bubble point test technique using the bubble point test kit was practical for routine quality control tests of PET radiopharmaceuticals.
Keywords: Sterilizing filtration; Integrity test; Bubble point test; PET radiopharmaceutical

Is it time to validate the prognostic role of F-18-FDG PET/CT scan in thymic epithelial tumors? by Filippo Lococo; Alfredo Cesario; Giorgio Treglia (593-594).

Clinical practice guideline for dedicated breast PET by Makoto Hosono; Tsuneo Saga; Kengo Ito; Shinichiro Kumita; Masayuki Sasaki; Michio Senda; Jun Hatazawa; Hiroshi Watanabe; Hiroshi Ito; Shinichi Kanaya; Yuichi Kimura; Hideo Saji; Seishi Jinnouchi; Hiroyoshi Fukukita; Koji Murakami; Seigo Kinuya; Junichi Yamazaki; Mayuki Uchiyama; Koichi Uno; Katsuhiko Kato; Tsuyoshi Kawano; Kazuo Kubota; Takashi Togawa; Norinari Honda; Hirotaka Maruno; Mana Yoshimura; Masami Kawamoto; Yukihiko Ozawa (597-602).