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Annals of Nuclear Medicine (v.24, #3)

Normal values for nuclear cardiology: Japanese databases for myocardial perfusion, fatty acid and sympathetic imaging and left ventricular function by Kenichi Nakajima (pp. 125-135).

Myocardial normal databases for stress myocardial perfusion study have been created by the Japanese Society of Nuclear Medicine Working Group. The databases comprised gender-, camera rotation range- and radiopharmaceutical-specific data-sets from multiple institutions, and normal database files were created for installation in common nuclear cardiology software. Based on the electrocardiography-gated single-photon emission computed tomography (SPECT), left ventricular function, including ventricular volumes, systolic and diastolic functions and systolic wall thickening were also analyzed. Normal databases for fatty acid imaging using ¹²³I-beta-methyl-iodophenyl-pentadecanoic acid and sympathetic imaging using ¹²³I-meta-iodobenzylguanidine were also examined. This review provides lists and overviews of normal values for myocardial SPECT and ventricular function in a Japanese population. The population-specific approach is a key factor for proper diagnostic and prognostic evaluation.

Keywords: Normal database; Myocardial perfusion imaging; Systolic and diastolic function; ¹²³I-BMIPP database; ¹²³I-MIBG database

Normal values for nuclear cardiology: Japanese databases for myocardial perfusion, fatty acid and sympathetic imaging and left ventricular function by Kenichi Nakajima (pp. 125-135).

Keywords: Normal database; Myocardial perfusion imaging; Systolic and diastolic function; ¹²³I-BMIPP database; ¹²³I-MIBG database

Imaging pharmacodynamics in oncology: the potential significance of “flares” by Ioannis Trigonis; Alan Jackson (pp. 137-147).

The clinical use of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography in monitoring anticancer treatment is expanding. At the same time a number of radiotracers aiming to image different aspects of tumour biology such as proliferation and apoptosis are being developed. However, the factors determining changes of radiotracer uptake parameters in response to treatment are not well understood. In many cases, cellularity may be the primary determinant of changes of FDG uptake and may confound the interpretation of metabolic changes. Early imaging assessments have in some cases showed transient increases of uptake parameters, commonly termed “flares”, which are likely to be unaffected by cellularity and directly reflect pharmacodynamics at a cellular level. In this review a number of settings where molecular imaging “flares” have been described are discussed. Such changes may often be clinically informative and warrant careful study as potential predictive biomarkers.

Keywords: PET; FDG; FLT; Flare response; Oncology

An efficient and aseptic preparation of “sodium fluoride (¹⁸F) injection” in a GMP compliant facility by Chih-Hao K. Kao; Wen-Lin Hsu; Pan-Fu Kao; Wen-Chun Lan; Heng-Li Xie; Ming-Chi Lin; Hao-Yu Chao (pp. 149-155).

“Sodium fluoride (¹⁸F) injection” is an isotonic NaCl solution containing [¹⁸F]NaF to be used as bone imaging agent. Although its NDA was approved by the US FDA in 1972, it has not been commercially available since 1975 due to mostly the popularity of ^99mTc-MDP. Recently, advances in PET/CT technology and the often interrupted ^99mTc supply have led to the renewed interest in the use of [¹⁸F]NaF to detect bone metastases in cancer patients. This report introduces an efficient, low-cost and aseptic preparation of “Sodium fluoride (¹⁸F) injection” for PET scan. ¹⁸F-Fluoride in target water from cyclotron was adsorbed onto four different forms of anion-exchange resins then desorbed by isotonic NaCl solution into the product vial. One of the resins that yielded the product at the suitable pH was used for the aseptic preparation. The components for this setup, including stopcocks, extension tubes, etc., were all single-use, individually packed and sterile. The process was done in a lead-line isolator maintained in grade A (PIC/S) aseptic condition. The quality of the obtained “Sodium fluoride (¹⁸F) injection” was analyzed according to its monograph in the European Pharmacopoeia (EP).The resin in the chloride form yielded the product of pH 6.7 and was chosen for the subsequent preparation. The radiochemical yield was quantitative. The product met all criteria specified in EP, including biological, physical and chemical specifications.This method is an efficient, space-saving and extremely low-cost operation that easily performed in an aseptic environment meeting GMP standard. The quality of the “Sodium fluoride (¹⁸F) injection” so yielded meets EP specifications. This setup provides hospital with facility meeting GMP standard a cost effective and efficient method for “Sodium fluoride (¹⁸F) injection” production without the need for the expensive automatic module and extra QC instrument.

Keywords: Sodium fluoride (¹⁸F) injection; [¹⁸F]NaF; Bone scan; PET drug GMP; European pharmacopoeia

Associations between liver ¹⁸F fluoro-2-deoxy-d-glucose accumulation and various clinical parameters in a Japanese population: influence of the metabolic syndrome by Kiyohisa Kamimura; Shigeki Nagamachi; Hideyuki Wakamatsu; Ryutaro Higashi; Mikio Ogita; Shin-ichiro Ueno; Seigo Fujita; Yoshiro Umemura; Toshiro Fujimoto; Masayuki Nakajo (pp. 157-161).

Liver demonstrates a heterogeneous ¹⁸F fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake pattern and sometimes shows an abnormally increased uptake even when there is no malignant tissue. The aim of this study was to evaluate the relationships of liver ¹⁸F-FDG uptake as related to physical factors, fatty liver, blood glucose (BG), and other biochemical data. ¹⁸F-FDG positron emission tomography (PET) imaging was performed in 101 consecutive subjects for cancer screening. Multiple stepwise regression analysis was used to define the best predictors of the liver standardized uptake value (SUV) among height, weight, waist circumference, body mass index (BMI), systolic and diastolic blood pressure, BG and other biochemical data, i.e., aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, total protein, total bilirubin, and alkaline phosphatase. Furthermore, we evaluated the association between liver ¹⁸F-FDG uptake and the metabolic syndrome.The independent factors for increased liver ¹⁸F-FDG uptake (mean SUV >= 2) were BMI (P < 0.0001), triglycerides (P = 0.0007), and high-density lipoprotein cholesterol (P = 0.0013). Other factors were not significantly associated with liver ¹⁸F-FDG uptake. In addition, the liver ¹⁸F-FDG uptake of metabolic syndrome subjects was significantly higher than that of a non-metabolic syndrome subjects.BMI was the strongest determinant of liver ¹⁸F-FDG uptake, and the liver ¹⁸F-FDG uptake of metabolic syndrome subjects was significantly higher than that of non-metabolic syndrome subjects. This result suggests that a subject with a high liver ¹⁸F-FDG uptake should be screened for the metabolic syndrome.

Keywords: ¹⁸F-FDG PET; Liver; Body mass index; Metabolic syndrome

Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [¹¹C]PK11195 in rats by Fumitaka Ito; Hiroshi Toyama; Gen Kudo; Hiromi Suzuki; Kentaro Hatano; Masanori Ichise; Kazuhiro Katada; Kengo Ito; Makoto Sawada (pp. 163-169).

The transition of microglia from the normal resting state to the activated state is associated with an increased expression of peripheral benzodiazepine receptors (PBR). The extent of PBR expression is dependent on the level of microglial activation. A PBR ligand, [¹¹C]PK11195, has been used for imaging of the activation of microglia in vivo. We evaluated whether [¹¹C]PK11195 PET can indicate differences of microglial activation between no treatment and lipopolysaccharide (LPS) treatment in a rat artificial injury model of brain inflammation.On day 1, a small aliquot of absolute ethanol was injected into the rat right striatum (ST) to produce artificial brain injury. On day 3, MRI scans were performed to evaluate and select rats showing a similar degree of brain injury. Then LPS or vehicle was administered intraperitoneally. On day 4, PET scans were performed after a bolus injection of [¹¹C]PK11195. Eleven rats (7 LPS administered rats, 4 LPS non-administered rats) were evaluated. We used uptake ratios of the integral of right and left striatum from 0 to 60 min as an estimate of PBR distribution volume (V ₆₀). The number of activated microglia and mRNA expression of inflammatory cytokines (TNFα, IL-1β) were assessed by isolectin-B4 staining and RT-PCR, respectively.Right/left ST V ₆₀ ratios of LPS group were significantly higher than those of non-LPS group (P < 0.03). Although there were no significant differences in the number of activated microglia between the two groups, LPS group showed higher expression of inflammatory cytokines (TNFα, IL-1β) than the non-treated group indicating that further activation was induced by LPS treatment.The results suggest that intensity of PBR signals in [¹¹C]PK11195 PET may be related to the level of microglial activation rather than the number in activated microglia at least in an artificial brain injury model.

Keywords: Peripheral benzodiazepine receptor; Animal PET; Activated microglia; Toxic conversion; Lipopolysaccharide

The reproducibility of deep-inspiration breath-hold ¹⁸F-FDG PET/CT technique in diagnosing various cancers affected by respiratory motion by Shigeki Nagamachi; Hideyuki Wakamatsu; Shogo Kiyohara; Seigo Fujita; Shigemi Futami; Hideo Arita; Shozo Tamura; Keiichi Kawai (pp. 171-178).

The deep-inspiration breath-hold PET/CT (DIBH PET/CT) technique improves the limitations of diagnosing a lesion located in an area influenced by respiratory motion that results in spatial misregistrations caused by respiration between PET and CT. However, its reproducibility with regard to calculating the maximal standardized uptake value (SUV_max) and metabolic volume (MV) in DIBH PET/CT has not been elucidated.The purpose of this study was to investigate the reproducibility of the DIBH PET/CT technique including calculating the SUV_max and the MV.Sixty patients with various cancers were enrolled. The subjects had 47 abdominal lesions and 28 chest lesions. All patients demonstrated a misregistered image in the early whole-body image taken 50 min after FDG intravenous infusions. We added the delayed spot images 40 min after the first image. On the delayed image, we performed both conventional techniques with non-breath-hold (NBH) and the DIBH technique. In the four times DIBH technique, we obtained the coefficient of variance (CV) in calculating these indices for evaluating reproducibility.The SUV_max value with DIBH showed an increase of 16.1–60.1% compared with that measured by NBH. The mean value of CV was 5.5 in thoracic lesions and 6.3 in abdominal lesions. The values of MV with DIBH showed a decrease of 14.0–20.1% compared with those measured by NBH. Regarding reproducibility, mean value of CV was 7.1 in thoracic lesions and 11.9 in abdominal lesions.The DIBH technique improves the inaccurate quantification of both SUV_max and MV. Although the CV value of SUV_max with DIBH technique is better in thoracic lesions compared with that in abdominal lesions, the reproducibility was acceptable.

Keywords: ¹⁸F-FDG PET/CT; Deep-inspiration breath-hold; Reproducibility

Multi-bed-position acquisition technique for deep inspiration breath-hold PET/CT: a preliminary result for pulmonary lesions by Hiromitsu Daisaki; Hiroyuki Shinohara; Takashi Terauchi; Takeshi Murano; Naoki Shimada; Noriyuki Moriyama; Ukihide Tateishi (pp. 179-188).

The deep inspiration breath-hold (DIBH) technique for positron emission tomography/computed tomography (PET/CT) is under investigation for its contribution to the accurate diagnosis of pulmonary lesions. “Step and shoot” or multi-bed-position image acquisition is necessary to improve the accuracy of whole-lung evaluation. The purpose of this study was to describe the method and preliminary results of evaluating pulmonary lesions using multi-bed-position deep inspiration breath-hold (MDIBH) PET/CT.Thirteen patients with a total of 32 metastatic pulmonary lesions underwent both whole-body free-breath (FB) and whole-lung MDIBH-PET/CT sessions with suitable axial slice overlap. The self-breath holding technique was used for reproducibility of the DIBH condition. The standard FB-PET/CT was performed under the FB condition, which was followed by the MDIBH-PET/CT performed under the DIBH condition. Accuracy of alignment between CT and PET images and CT image quality were evaluated independently on dependent density, motion artifact, and heterogeneity attenuation. Mean standardized uptake value (SUV) in normal lung [Background (BG)-SUV_mean], maximum SUV (SUV_max) of lesion (lesion-SUV_max), tumor background ratios (TBRs), and uptake volumes (UVs) were evaluated quantitatively.Improvements in artifacts were statistically significant using MDIBH-PET/CT. Improvements in alignment were statistically significant with the MDIBH-PET/CT for the diaphragm, heart and lung apices. CT image quality was statistically significantly higher with the MDIBH-PET/CT than with the FB-PET/CT in all indices. The decreases in BG-SUV_mean were statistically significant (in all patients) with an average of −37%. Lesion-SUV_max was increased in 7 of 32 (22%) lesions although average lesion-SUV_max showed no statistical difference between the FB- and the MDIBH-PET/CT images. The increase in TBRs was statistically significant in 31 of 32 lesions (97%) in the MDIBH-PET/CT with an average of 57%. UVs were lower in 23 of 32 lesions (72%) in the MDIBH-PET/CT by −12% on average, although no statistical difference was confirmed between the techniques.The MDIBH-PET/CT can provide better-aligned fused images, featuring superior image quality, in both PET and CT images. The PET images showed low BG, non-blurring and high TBRs, and the CT images provided diagnostic capability of detecting small pulmonary lesions with negligible radiation exposure.

Keywords: FDG; PET/CT; Breath-hold; Pulmonary; Cancer

^99mTc-DTPA dynamic SPECT and CT volumetry for measuring split renal function in live kidney donors by Chihoko Miyazaki; Hiroshi Harada; Noriyuki Shuke; Atsutaka Okizaki; Masayoshi Miura; Tetsuo Hirano (pp. 189-195).

Split renal function (SRF) estimated from the posterior view of ^99mTc-diethylenetriaminepentaacetic acid planar scintigraphy (DTPA/P) is not sufficiently accurate even after correction for kidney depth by computed tomography (CT). To obtain more accurate SRF using ^99mTc-DTPA, dynamic SPECT method was carried out for the initial 5 min after bolus injection of ^99mTc-DTPA (DTPA/SPECT). Also SRF was evaluated from the renal volume measured by CT. We compared the results with ^99mTc-dimercaptosuccinic acid SPECT (DMSA/SPECT).In 60 consecutive live kidney donors, 30 DTPA/P, 30 DTPA/SPECT, 60 ^99mTc-DMSA/SPECT, and 60 CT studies were performed. In the DTPA/P studies, SRF was calculated from the posterior image recorded during 2–3-min postinjection with attenuation correction for kidney depth measured by CT. In the DTPA/SPECT studies, SPECT images were acquired continuously for 5 min with a dual-headed gamma camera. In ^99mTc-DMSA scintigraphy, DMSA/SPECT images were acquired 3-h postinjection. The SRF on both SPECT studies was calculated from the total counts of each kidney. In the DTPA/SPECT study, SRF was evaluated on the three images summed for 1 min: 1–2 min (DTPA/SPECT1–2), 2–3 min (DTPA/SPECT2–3), and 1–3 min (DTPA/SPECT1–3). In the CT examination, to assess the global renal volume, the axial images in the excretory phase were chosen. Renal contours were identified on each image, and the areas (cm²) of these regions were summed and multiplied by the slice thickness (10 mm) to yield global renal volume (ml). Right renal function from DTPA/P, DTPA/SPECT, and CT were compared with that from DMSA/SPECT as a reference.Correlation coefficients of the right renal function between DMSA/SPECT and DTPA/P, DTPA/SPECT2–3, and CT were 0.663, 0.849 and 0.907, respectively (P < 0.0001). The differences between DMSA/SPECT and DTPA/P, DTPA/SPECT2–3 and CT were 2.42 ± 3.878, 0.867 ± 1.672, and −0.421 ± 1.077% (mean ± SD), respectively.SRF derived from DTPA/SPECT showed a better correlation with DMSA/SPECT and significantly fewer errors (P < 0.05) than DTPA/P. A significant strong correlation was observed between SRF from DMSA/SPECT and CT, indicating the utility of CT renal volumetry for evaluating SRF.

Keywords: Split renal function; Live kidney donor; ^99mTc-DTPA; SPECT; CT

Estimation of local statistical noise in PET images induced by attenuation inside the body by Hideaki Kitamura; Kazumasa Inoue; Tatsuya Sasaki; Keisuke Tsuda; Hirotaka Fujimori; Takashi Tanaka; Masahiro Fukushi; Noriyuki Moriyama; Hirofumi Fujii (pp. 197-205).

In positron emission tomography/computed tomography (PET/CT) examinations, the standardized uptake value (SUV) is a commonly used index to evaluate the activity of cancer. The precision of SUV is directly affected by the local statistical noise in PET images because SUV is calculated based on the counts on PET image data. The purpose of this study was to estimate the local statistical noise in the PET image caused by attenuation of annihilation photons inside the body.To estimate the local statistical noise, we defined the number proportional to the standard deviation of a voxel caused by attenuation using CT image data. The conversion table between the number obtained from the CT image data and the actually measured standard deviation of a voxel was made by performing experiments with different forms or sizes of phantoms and scattering bodies. We compared the standard deviation of a voxel estimated by the method we proposed with actually measured ones.The standard deviation of a voxel in the PET image varied according to the size of the phantom. The effect of attenuation on the standard deviation of a voxel was more significant in the 3D mode than in the 2D mode. The correlation coefficients between the estimated standard deviation and actually measured standard deviation were 0.98 and 0.99 in the 2D mode and 3D mode, respectively.Our algorithm favorably estimated the local statistical noise in PET image data using CT image data, regardless of object size, although the consideration was limited for phantoms with homogeneous interiors.

Keywords: Positron emission tomography; Noise; Attenuation

¹⁸F-FDG PET-CT respiratory gating in characterization of pulmonary lesions: approximation towards clinical indications by A. M. García Vicente; A. M. Soriano Castrejón; M. P. Talavera Rubio; A. A. León Martín; A. M. Palomar Muñoz; J. P. Pilkington Woll; V. M. Poblete García (pp. 207-214).

To evaluate the effect of the 18F-FDG PET-CT respiratory gating (4D) study in the correct documentation of pulmonary lesions with faint uptake in standard PET-CT.Forty-two pulmonary lesions with a low or no detectable uptake of FDG (SUV_max < 2.5) in 3D PET-CT were prospectively evaluated in 28 patients (19 males and 9 females), mean age 66.5 years (41–81). 22 patients had neoplastic background. A conventional PET-CT (3D) total body scan was performed approximately 60 min after iv injection of a mean dose of 370 MBq. Furthermore, a 4D PET-CT (synchronized with respiratory movement) thorax study was acquired. SUV_max was determined for each lesion in both studies. For the 4D studies, we selected the SUV_max in respiratory period with the highest uptake (“best bin”). We calculated the SUV_max percentage difference between 3D and 4D PET-CT (% difference = SUV_max 4D − SUV_max 3D/SUV_max 3D × 100) and the relation of this value with the size and locations of the lesions. In 4D study, any lesion with SUV_max ≥ 2.5 was classified as malignant. We assessed the changes of lesion classification (from benign to malignant) applying the 4D technique. The final diagnosis was obtained by histological assessment or clinical and radiological follow-up longer than 12 months.Forty out of 42 lesions showed an increase of SUV_max in the 4D study with respect to 3D. The mean SUV_max in the 3D and 4D PET-CT studies were 1.33 (±0.59) and 2.26 (±0.87), respectively. The SUV_max percentage difference mean between both techniques was 83.3% (±80.81).The smaller the lesion the greater was the SUV_max percentage difference (P < 0.05). No differences were observed depending on the location of the lesion. In 40% of cases, there was a change in the final classification of lesions from benign to malignant. In the final diagnosis, 24 lesions were malignant. 4D PET-CT diagnosed correctly the 52% of them.The 4D PET-CT study permitted a better characterization of malignant lung lesions compared with the standard PET-CT, because of its higher sensitivity. 4D PET-CT is a recommendable technique in the early diagnosis of malignant lesions.

Keywords: PET-CT; Respiratory gating; Pulmonary lesions

Clinical significance of ischemic electrocardiographic changes during stress myocardial perfusion imaging: sub-analysis of the J-ACCESS study by Kazuya Takehana; Shigeyuki Nishimura; Hirofumi Maeba; Takanao Ueyama; Toshiji Iwasaka; Tsunehiko Nishimura (pp. 215-224).

The cardiac event rate among the countries varies according to ethnicity. Some reports have identified that ischemic heart disease often occurs at a low incidence and is often milder in Japan compared to other countries. Therefore, the present study was designed to determine the clinical significance and prediction for cardiac events in patients who showed ischemic ECG changes during stress myocardial perfusion SPECT.Among 4,670 registered patients for Japanese-assessment of cardiac event and survival (J-ACCESS) study, patients with conduction abnormality on baseline were excluded and revascularization within 60 days of SPECT study were censored from the prognostic portion of analysis. Stress and rest myocardial perfusion SPECT imaging with ^99mTc-tetrofosmin were performed and occurrence and nature of cardiac events were investigated at 1, 2 and 3 years after registration. Both PCI and CABG, as well as recurrent angina and non-severe heart failure were classified as soft events. Cardiac death, non-fatal MI and heart failure requiring hospitalization were classified as major cardiac events, and hard events comprised cardiac death and non-fatal MI.A total of 3,125 patients performed exercise (n = 2,383) or vasodilator (n = 742) stress MPI and significant ischemic ECG changes were obtained in 538 during exercise and 35 during vasodilator stress. Kaplan–Meier analysis revealed that the patients with both ischemic ECG changes and reversible perfusion defect on MPI had significantly higher incidence for major cardiac events, such as cardiac death, non-fatal MI and severe heart failure (P = 0.0038), and for cardiac hard events, such as cardiac death and non-fatal MI (P = 0.0028), in exercise stress. Interestingly, patients without reversible perfusion defect showed significantly fewer events despite presence of ischemic ECG changes.Ischemic ECG changes during exercise stress are well associated with higher incidence of cardiac events in patients demonstrated reversible perfusion defect on MPI.

Keywords: Stress myocardial perfusion SPECT; Ischemic ECG changes; Prognosis

¹⁸F-Fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of idiopathic retroperitoneal fibrosis associated with mediastinal fibrosis by Satoshi Washino; Masaru Hirai; Atsushi Matsuzaki; Yutaka Kobayashi (pp. 225-229).

A 68-year-old man was admitted to our hospital with left intermittent claudication. Computed tomography showed soft tissue masses surrounding the left iliac artery and in the bilateral pulmonary hilum, and the first FDG PET showed increased FDG uptake by the lesions. Retroperitoneal fibrosis associated with mediastinal fibrosis was most suspected. An open biopsy of the left peri-iliac masses revealed retroperitoneal fibrosis. Corticosteroid treatment was initiated. The second FDG PET under corticosteroid treatment showed no pathological FDG uptake. The third FDG PET after cessation of corticosteroid treatment showed increased FDG uptake in the mediastinum, and so Sairei-to treatment was initiated. The fourth FDG PET under Sairei-to treatment showed no improvement of the pathological FDG uptake, and so low-dose corticosteroid was re-started in combination with Sairei-to treatment. The fifth FDG PET under Sairei-to and corticosteroid treatment showed no pathological FDG uptake. These FDG PET findings suggest the usefulness of FDG PET for the diagnosis and monitoring of retroperitoneal fibrosis associated with mediastinal fibrosis.

Keywords: Retroperitoneal fibrosis; Mediastinal fibrosis; FDG PET

Erratum to: Fluoro-deoxy-glucose positron emission tomography for evaluation of indeterminate lung nodules: assigning a probability of malignancy may be preferable to binary readings by Suk Chul Kim; Josef Machac; Borys R. Krynyckyi; Karin Knesaurek; Daniel Krellenstein; Barbara Schultz; Allen Gribetz; Louis DePalo; Alvin Teirstein; Chun K. Kim (pp. 231-231).

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Annals of Nuclear Medicine (v.24, #3)