Annals of Nuclear Medicine (v.30, #6)

The objective of the systematic review and meta-analysis was to evaluate whether the choice between two radiotracers, 11C-choline (11C-cho) and 18F-fluorocholine (18F-FCH) for PET/CT, and different acquisition protocols contributed to detect metastases for patients with biochemical recurrence of prostate cancer after radical prostatectomy or radiotherapy. We searched in January 2016 in Pubmed and Embase for articles that had used radiolabeled choline PET/CT in restaging. The meta-analysis evaluated technical and clinical aspects. Across 18 articles 1 219 of 2 213 patients (54.9 %) had a positive radiolabeled PET/CT image. Mean of the mean/median restaging PSA levels was 3.6 ± 2.7 ng/mL (range 0.5–10.7 ng/mL). Six articles with 11C-cho PET/CT had a radiation activity of 561 ± 122 MBq and it was 293 ± 47 MBq in 12 articles with 18F-FCH PET/CT. The difference was significant (P = 0.007, t test). Uptake time was 5 min in articles with 11C-cho PET/CT and it was 29 ± 24 min in articles with 18F-FCH PET/CT. The difference was significant (P = 0.02, t test). Thereby the detection rates of metastatic sites in articles with 11C-cho (30 ± 5 %) and 18F-FCH (39 ± 5 %) did not differ significantly (P = 0.26, t test). In linear regression analyses of the articles, the radiation activity of 11C-cho and 18F-FCH was not significantly associated with the detection rate of metastatic sites (P = 0.75 and P = 0.60). Restaging with radiolabeled choline PET/CT detected metastatic sites for patients with biochemical recurrence and PSA levels of 1–10 ng/mL at clinically relevant level. The choice between the two choline radiotracers and different acquisition protocols had no significant impact on detection.
Keywords: Acquisition protocol; Biochemical recurrence; 11C-Choline PET/CT; 18F-Fluorocholine PET/CT; Meta-analysis; Prostatic neoplasms; Restaging

The influence of respiratory motion on the cumulative SUV-volume histogram and fractal analyses of intratumoral heterogeneity in PET/CT imaging by Toshiki Takeshita; Keishin Morita; Yuji Tsutsui; Daisuke Kidera; Shohei Mikasa; Akira Maebatake; Go Akamatsu; Kenta Miwa; Shingo Baba; Masayuki Sasaki (393-399).
The purpose of this study was to investigate the influence of respiratory motion on the evaluation of the intratumoral heterogeneity of FDG uptake using cumulative SUV-volume histogram (CSH) and fractal analyses.We used an NEMA IEC body phantom with a homogeneous hot sphere phantom (HO) and two heterogeneous hot sphere phantoms (HE1 and HE2). The background radioactivity of 18F in the NEMA phantom was 5.3 kBq/mL. The ratio of radioactivity was 4:2:1 for the HO and the outer rims of the HE1 and HE2 phantoms, the inner cores of the HE1 and HE2 phantoms, and background, respectively. Respiratory motion was simulated using a motion table with an amplitude of 2 cm. PET/CT data were acquired using Biograph mCT in motionless and moving conditions. The PET images were analyzed by both CSH and fractal analyses. The area under the CSH (AUC-CSH) and the fractal dimension (FD) was used as quantitative metrics.In motionless conditions, the AUC-CSHs of the HO (0.80), HE1 (0.75) and HE2 (0.65) phantoms were different. They did not differ in moving conditions (HO, 0.63; HE1, 0.65; HE2, 0.60). The FD of the HO phantom (0.77) was smaller than the FDs of the HE1 (1.71) and HE2 (1.98) phantoms in motionless conditions; however, the FDs of the HO (1.99) and HE1 (2.19) phantoms were not different from each other and were smaller than that of the HE2 (3.73) phantom in moving conditions.Respiratory motion affected the results of the CSH and fractal analyses for the evaluation of the heterogeneity of the PET/CT images. The influence of respiratory motion was considered to vary depending on the object size.
Keywords: PET/CT; Cumulative SUV-volume histogram analysis; Fractal analysis; Respiratory motion

Development of a 68Ga-peptide tracer for PET GnRH1-imaging by Masoumeh Zoghi; Amir R. Jalilian; Ali Niazi; Fariba Johari-daha; Behrouz Alirezapour; Saeed Ramezanpour (400-408).
Total synthesis, quality control and preclinical evaluation of [68Ga]-DOTA-triptorelin ([68Ga]-DOTA-TRP) is reported as a possible PET radiotracer for GnRH receptor imaging.DOTA-TRP was totally synthesized in two steps and after characterization went through radiolabelling optimization studies followed by tracer stability. The biodistribution of the tracer in normal male rats and 4T1 tumour-bearing mice was performed in 120 min after i.v. injection.The peptide and the conjugates were synthesized with >95 % chemical purity. [68Ga]-DOTA-TRP complex was prepared in high radiochemical purity (>99 %, ITLC, HPLC) and specific activity of 1400–2100 MBq/nM at 95 °C using 40–60 μg of the peptide in 5–7 min followed by solid phase purification. The IC50 [nM] DOTA-TRP was comparable to the intact peptide, 0.11 ± 0.01 and 0.22 ± 0.05, respectively. The biodistribution of the tracer demonstrated kidney, stomach, and testes significant uptake, all in accordance with GnRH receptor ligands. Significant tumour uptake was observed in 4T1 tumour-bearing female mice 30–120 min post-injection with tumour:blood and tumour:muscle ratios of 28 and >50 in 60 min, respectively. Kidney is rapidly washed from the tracer. [68Ga]-DOTA-TRP can be proposed as a possible tracer for GnRH-R imaging studies.
Keywords: 68Ga; Triptorelin; Peptide synthesis; 4T1; GnRH

18F-FDG uptake in main arterial branches of patients with large vessel vasculitis: visual and semiquantitative analysis by Massimo Castellani; Manuela Vadrucci; Luigia Florimonte; Monica Caronni; Riccardo Benti; Paola Bonara (409-420).
Over the last decade, the contribution of 18F-FDG (FDG) PET/CT imaging to the diagnosis of large vessel vasculitis has been widely investigated. The aim of this study was to evaluate a more extensive role for PET/CT in grading vascular inflammation in patients with different clinical stages of disease.The images of 66 PET/CT studies of 34 patients, performed at diagnosis and/or during follow-up were reviewed. FDG uptake in different regions of aorta and in its major branches was visually (regional Score: rS) and semiquantitatively (regional SUVmean: rSUV) assessed. The global vascular uptake was also evaluated for each study by summing all rSs (summed Score; sS) and averaging rSUVs (averaged SUV; aSUV). FDG uptake in 15 PET/CT studies of control age-matched subjects without signs or symptoms of vasculitis was also analyzed.Higher levels of regional and global FDG uptake were found at diagnosis in comparison with follow-up studies of 12 patients with complete longitudinal observation (p value range 0.0552–0.0026). In the latter group high values were generally observed when disease relapse or incomplete response to therapy (active disease) occurred, whereas lower uptake was found in studies of remitted patients (p = <0.01), whose FDG levels were similar to those of control subjects. At ROC analysis performed on all image dataset, optimal cut-off levels of regional and global FDG vascular uptake provided a good discrimination between 25 patients at diagnosis and 15 control subjects (aSUV greater than 0.697; PPV = 92.3; NPV = 92.9). Major overlap was observed among FDG levels of 21 patients with active disease and in remission (aSUV greater than 0.653; PPV = 58.3; NPV = 94.1). Similar performances of visual and semiquantitative analyses were found when areas under curves (AUCs) were compared. 18F-FDG PET/CT has a promising role in grading inflammation in patients with large arteries vasculitis. Nevertheless, a cut-off based analysis of FDG vascular uptake is not sufficient to separate patients with active and inactive disease during follow-up.
Keywords: PET/CT; Large vessel vasculitis; Inflammation; SUV analysis

The cingulate island sign (CIS), which refers to sparing of the posterior cingulate relative to the precuneus and cuneus, has been proposed as an FDG-PET imaging feature of dementia with Lewy bodies (DLB). The sign is reportedly associated with Alzheimer’s disease (AD) type neurofibrillary tangle (NFT) pathology in autopsy cases. To confirm this relationship using neuroimaging modalities in vivo, we investigated associations between CIS and the medial temporal lobe (MTL) atrophy in DLB.Twenty-four patients each of DLB and AD underwent both 18F-FDG-PET and MRI with voxel-based morphometry. Dopamine transporter (DAT) density was also measured by DAT-SPECT in all those with DLB and in five with AD. The accumulation of FDG in the posterior cingulate ROI was divided by that in the precuneus plus cuneus ROI to derive the CIS ratio from the FDG-PET images. Values for cognitive function of Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Ray Auditory Verbal Learning Test (RAVLT) and scores for the core-feature triad of fluctuation, hallucination and parkinsonism were also statistically analyzed.The CIS ratio was higher in DLB than in AD (p < 0.001). The degree of MTL atrophy was lower in DLB than in AD (p < 0.001). The CIS ratio and the degree of MTL atrophy were inversely correlated with DLB (p < 0.001) and with AD (p < 0.05). The CIS ratio did not significantly correlate with DAT density in DLB or with MMSE, FAB, fluctuation score and parkinsonism score. However, the CIS ratio significantly correlated with RAVLT and hallucination scores (both, p < 0.05).The CIS on FDG-PET in DLB was associated with MTL atrophy but not with striatal DAT density, suggesting that the CIS is a useful neuroimaging biomarker to evaluate coexisting AD-type NFT pathology in vivo. The CIS was also associated with memory impairment and visual hallucination in DLB.
Keywords: Cingulate island sign; Medial temporal lobe; Dopamine transporter; Dementia with Lewy bodies

18F-fluoride PET/CT for detection of axial involvement in ankylosing spondylitis: correlation with disease activity by Luca Idolazzi; Matteo Salgarello; Davide Gatti; Ombretta Viapiana; Elisabetta Vantaggiato; Angelo Fassio; Silvano Adami; Maurizio Rossini (430-434).
Aim of the current study was to evaluate the relationships between the findings of 18F-fluoride PET/CT (F-PET/CT) reflecting osteo-proliferative processes and the clinical indexes related to the disease activity. The clinical indexes are Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS).We studied 29 AS patients aged 26–69 years with a wide range of disease activity using F-PET/CT. The number of regions of high bone turnover or osteoarthritis features at the spine and at sacroiliac joints was counted.The number of F-PET/CT positive sites was significantly higher in patients with severe functional impairment and higher disease activity and it was positively related to both BASDAI (r = 0.336; P = 0.036) and ASDAS (r = 0.408; P = 0.014) while the number of degenerative features (osteoarthritis) was related neither with functional impact nor with disease activity.With a single examination, F-PET/CT accurately identifies the functional impairment and the clinical involvement of AS. The good correlation we found between the number of F-PET/CT positive sites and disease activity candidates this technique also for follow-up of AS.
Keywords: 18F-fluoride PET; ASDAS; BASDAI; BASFI; Spondyloarthritis; Ankylosing spondylitis

Report of a nationwide survey on actual administered radioactivities of radiopharmaceuticals for diagnostic reference levels in Japan by Hiroshi Watanabe; Kazunari Ishii; Makoto Hosono; Etsuko Imabayashi; Koichiro Abe; Masayuki Inubushi; Kazuko Ohno; Yasuhiro Magata; Kinya Ono; Kei Kikuchi; Kei Wagatsuma; Tadashi Takase; Kyoko Saito; Yasuyuki Takahashi (435-444).
The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine.A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form.Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of 99mTc-MDP and 99mTc-HMDP: bone scintigraphy, 99mTc-HM-PAO, 99mTc-ECD and 123I-IMP: cerebral blood flow scintigraphy, 99mTc-Tetrofosmin, 99mTc-MIBI and 201Tl-Cl; myocardial perfusion scintigraphy and 18F-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq (99mTc-MDP and 99mTc-HMDP: bone scintigraphy), 740 MBq (99mTc-ECD and 99mTc-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq (99mTc-Tetrofosmin and 99mTc-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy (99mTc-MDP and 99mTc-HMDP), cerebral blood flow scintigraphy (99mTc-HM-PAO) and myocardial perfusion scintigraphy (99mTc-Tetrofosmin and 99mTc-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity.This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.
Keywords: Survey; Diagnostic reference level; Radiopharmaceutical; Radioactivity; Optimization of dose

Optimal HMPAO α value for Lassen’s correction algorithm obscured by statistical noise by Masashi Kameyama; Koji Murakami; Masahiro Jinzaki (445-449).
[99mTc] d,l-hexamethyl-propyeneamine oxime (99mTc-HMPAO), a brain perfusion tracer, suffers significant underestimation of regional cerebral blood flow (rCBF). Lassen et al. developed their linearization algorithm to correct the influence of back-diffusion of the tracer, and proposed their parameter α as 1.5. Based on mathematical modeling and literature review, recently, a new α value of 0.5 has been proposed for Lassen’s correction algorithm for 99mTc-HMPAO, although correction using the old α value of 1.5 was confirmed to be sufficient. Inugami et al. reported that linearization correction gives a stable correlation coefficient over a wide range of α. Our hypotheses are that statistical noise is the source of the stable correlation coefficient presented by them and that the robustness of the correlation coefficient is the reason why many studies confirmed the value of α as 1.5.Statistical noise was added in silico to the count, whose relationship with flow was α = 0.5. Then, the count was corrected by Lassen’s linearization algorithm with a variety of α.This study confirmed the hypothesis that smaller α values (strong correction) increase the noise at high flow values, leading to nominal increases in correlation coefficient as α decreases.Despite this, adoption of the new, smaller α value of 0.5 would be more useful clinically in regaining the contrast between low-flow and high-flow areas of the brain.
Keywords: Lassen’s linearization correction algorithm; 99mTc-HMPAO; Single photon emission computed tomography; Image contrast; Renkin–Crone’s equation

PEM or MBI? by Paweł Zdanowski; Leszek Królicki (450-451).

Reply to ‘PEM or MBI?’ by Yayoi Yamamoto (452-452).