Annals of Nuclear Medicine (v.31, #9)

IQ·SPECT technology and its clinical applications using multicenter normal databases by Kenichi Nakajima; Koichi Okuda; Mitsuru Momose; Shinro Matsuo; Chisato Kondo; Masayoshi Sarai; Takayuki Shibutani; Masahisa Onoguchi; Takeshi Shimizu; A. Hans Vija (649-659).
IQ·SPECT (Siemens Medical Solutions) is a solution for high-sensitivity and short-time acquisition imaging of the heart for a variable angle general purpose gamma camera. It consists of a multi-focal collimator, a cardio-centric orbit and advanced iterative reconstruction, modeling the image formation physics accurately. The multi-focal collimator enables distance-dependent enlargement of the center region while avoiding truncation at the edges. With the specified configuration and a cardio-centric orbit it can obtain a fourfold sensitivity increase for the heart at the center of the scan orbit. Since IQ·SPECT shows characteristic distribution patterns in the myocardium, appropriate acquisition and processing conditions are required, and normal databases are convenient for quantification of both normal and abnormal perfusion images. The use of prone imaging can be a good option when X-ray computed tomography (CT) is not available for attenuation correction. CT-based attenuation correction changes count distribution significantly in the inferior wall and around the apex, hence image interpretation training and additional use of normal databases are recommended. Recent reports regarding its technology, Japanese Society of Nuclear Medicine working group activities, and clinical studies using 201Tl and 99mTc-perfusion tracers in Japan are summarized.
Keywords: Myocardial perfusion imaging; Multifocal collimator; Attenuation correction; Prone imaging; Japanese Society of Nuclear Medicine (JSNM) normal database; Short-time acquisition

Prediction of outcome in pediatric Hodgkin lymphoma based on interpretation of 18FDG-PET/CT according to ΔSUVmax, Deauville 5-point scale and IHP criteria by Emine Göknur Isik; Serkan Kuyumcu; Rejin Kebudi; Yasemin Sanli; Zeynep Karakas; Fatma Betul Cakir; Seher Nilgün Unal (660-668).
Minimizing side effects by using response-adopted therapy strategies plays an important role in the management of pediatric Hodgkin lymphoma (HL); however, the criteria for the definition of adequate or inadequate response are controversial. The aim of this study is to compare different methods of interpretation of 18F-FDG-PET/CT (PET) in the prediction of disease outcome in order to determine the optimum method in this regard.Baseline, interim and post-treatment PET scans of 72 children were interpreted according to revised International Harmonization Project criteria (IHP) and Deauville criteria. Cut-off values for changes in interim and post-treatment FDG uptake (ΔSUVmax) in the prediction of progression-free survival (PFS) were measured using ROC analysis. Quantitative and visual data were compared with each other in the prediction of PFS.Mean interim and post-treatment ΔSUVmax of the primary lesions were 77.4 ± 19.5 and 68.8 ± 30.4% and respective cut-off values were 82 and 73%. However, only post-treatment ΔSUVmax yielded statistically significant results in the prediction of 3-year PFS (p = 0.043). Interim ΔSUVmax was further analyzed according to the values reported in the literature (66 and 77%) yet statistically significant results were not reached (p = 0.604 and 0.431). For interim evaluation, IHP criteria was correlated to Deauville criteria (p = 0.002 and p = 0.001) and ΔSUVmax (p = 0.03), whereas for post-treatment evaluation, significant correlation with ΔSUVmax (p = 0.04) but marginally significant (p = 0.055 and p = 0.058) correlation with Deauville criteria were achieved. Overall, 1, 3 and 5-year PFS were 95.7 ± 0.2, 89.6 ± 0.4 and 80.8 ± 0.7%, respectively. All methods demonstrated comparable performance in the prediction of 3-year PFS; however, interim PET using Deauville criteria and post-treatment PET using IHP criteria were statistically significant. All methods demonstrated high negative-predictive value but substantially low positive-predictive value.Deauville criteria are superior to other methods in the prediction of pediatric HL outcome using interim PET data. On the other hand, quantitative evaluation and visual evaluation by IHP can be used reliably at the end of the treatment. In this regard, we report the optimal cut-off value of SUVmax reduction as 73%.
Keywords: Deauville; Pediatric Hodgkin lymphoma; IHP criteria; FDG-PET/CT

Applying near-infrared photoimmunotherapy to B-cell lymphoma: comparative evaluation with radioimmunotherapy in tumor xenografts by Yusri-Dwi Heryanto; Hirofumi Hanaoka; Takahito Nakajima; Aiko Yamaguchi; Yoshito Tsushima (669-677).
Radioimmunotherapy (RIT) has proven effective for patients with relapsed and refractory lymphoma. However, new types of therapy are strongly desired as B-cell lymphoma remains incurable for many patients. Photoimmunotherapy (PIT) is an emerging targeted cancer therapy that uses photosensitizer (IR700)-conjugated monoclonal antibodies (mAbs) to specifically kill cancer cells. To evaluate the usefulness and potential role of PIT for treating B-cell lymphoma in a comparison with RIT, we performed in vivo PIT and RIT studies with an IR700 or 90Y-conjugated anti-CD20 mAb, NuB2.IR700 or 90Y were conjugated to NuB2. Since cell aggressiveness greatly affects the therapeutic effect, we selected both an indolent (RPMI 1788) and an aggressive (Ramos) type of B-cell lymphoma cell line. The in vitro therapeutic effect of PIT and the biodistribution profiles of IR700–NuB2 were evaluated. In vivo PIT and RIT studies were performed with 100 or 500 μg of IR700–NuB2 and 150 μCi/20 μg of 90Y-NuB2, respectively, in two types of B-cell lymphoma-bearing mice.The in vitro studies revealed that Ramos was more sensitive than RPMI 1788 to PIT. The therapeutic effect of PIT with 500 µg IR700–NuB2 was superior to any other therapies against aggressive Ramos tumors, whereas RIT showed the highest therapeutic effect in indolent RPMI 1788 tumors. Since the uptake levels and intratumoral distribution of IR700–NuB2 were comparable in both tumors, a possible cause of this difference is the tumor growth rate. The PIT with 500 µg (IR700–NuB2) group showed a significantly greater therapeutic effect than the PIT with 100 µg group due to the higher and more homogeneous tumor distribution of IR700–NuB2.PIT was effective for both indolent and aggressive B-cell lymphoma, and the higher dose provided a better therapeutic effect. In aggressive tumors, PIT was more effective than RIT. Thus, PIT would be a promising strategy for the locoregional treatment or control of B-cell lymphoma. Since PIT and RIT have distinctive advantages over each other, they could play complementary rather than competitive roles in B-cell lymphoma treatment.
Keywords: B-cell lymphoma; Anti-CD20 antibody; Radioimmunotherapy; Photoimmunotherapy

18F-FDG PET radiomics approaches: comparing and clustering features in cervical cancer by Tetsuya Tsujikawa; Tasmiah Rahman; Makoto Yamamoto; Shizuka Yamada; Hideaki Tsuyoshi; Yasushi Kiyono; Hirohiko Kimura; Yoshio Yoshida; Hidehiko Okazawa (678-685).
The aims of our study were to find the textural features on 18F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between 18F-FDG PET textural features in cervical cancer.Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment 18F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively. These features were compared between SCC and NSCC using a Bonferroni adjusted P value threshold of 0.0028 (0.05/18). To assess the association between PET features, a heat map analysis with hierarchical clustering, one of the radiomics approaches, was performed.Among 18 PET features, correlation, a second-order textural feature derived from NGLCM, was a stable parameter and it was the only feature which showed a robust trend toward significant difference between SCC and NSCC. Cervical SCC showed a higher correlation (0.70 ± 0.07) than NSCC (0.64 ± 0.07, P = 0.0030). The other PET features did not show any significant differences between SCC and NSCC. A higher correlation in SCC might reflect higher structural integrity and stronger spatial/linear relationship of cancer cells compared with NSCC. A heat map with a PET feature dendrogram clearly showed 5 distinct clusters, where correlation belonged to a cluster including MTV and TLG. However, the association between correlation and MTV/TLG was not strong. Correlation was a relatively independent PET feature in cervical cancer. 18F-FDG PET textural features might reflect the differences in histological architecture between cervical cancer subtypes. PET radiomics approaches reveal the association between PET features and will be useful for finding a single feature or a combination of features leading to precise diagnoses, potential prognostic models, and effective therapeutic strategies.
Keywords: PET; Textural feature; Cervical cancer; Radiomics

This study aimed to compare the qualities of whole-body positron emission tomography (PET) images acquired by the step-and-shoot (SS) and continuous bed motion (CBM) techniques with approximately the same acquisition duration, through phantom and clinical studies.A body phantom with 10–37 mm spheres was filled with 18F-fluorodeoxyglucose (FDG) solution at a sphere-to-background radioactivity ratio of 4:1 and acquired by both techniques. Reconstructed images were evaluated by visual assessment, percentages of contrast (%Q H) and background variability (%N) in accordance with the Japanese guideline for oncology FDG-PET/computed tomography (CT). To evaluate the variability of the standardized uptake value (SUV), the coefficient of variation (CV) for both maximum SUV and peak SUV was examined. Both the SUV values were additionally compared with those of standard images acquired for 30 min, and their accuracy was evaluated by the %difference (%Diff). In the clinical study, whole-body 18F-FDG PET/CT images of 60 patients acquired by both techniques were compared for liver signal-to-noise ratio (SNRliver), CV at end planes, and both SUV values.In the phantom study, the visual assessment and %Q H values of the two techniques did not differ from each other. However, the %N values of the CBM technique were significantly higher than those of the SS technique. Additionally, the CV and %Diff for both SUV values in the CBM images tended to be slightly higher than those in SS images. In the clinical study, the SNRliver values of CBM images were significantly lower than those of SS images, although the CV at the end planes in CBM images was significantly lower than those in SS images. In the Bland–Altman analysis for both SUV values, the mean differences were close to 0, and most lesions exhibited SUVs within the limits of agreement.The CBM technique exhibited slightly lesser uniformity in the center plane than the SS technique. Additionally, in the phantom study, the CV and %Diff of SUV values in CBM images tended to be slightly higher than those of SS images. However, since these differences were subtle, they might be negligible in clinical settings.
Keywords: Positron emission tomography (PET); Step-and-shoot (SS); Continuous bed motion (CBM); Whole body; Acquisition duration

Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted 18F-DCFPyL in peripheral ganglia by Rudolf A. Werner; Sara Sheikhbahaei; Krystyna M. Jones; Mehrbod S. Javadi; Lilja B. Solnes; Ashley E. Ross; Mohamad E. Allaf; Kenneth J. Pienta; Constantin Lapa; Andreas K. Buck; Takahiro Higuchi; Martin G. Pomper; Michael A. Gorin; Steven P. Rowe (696-702).
Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent 18F-DCFPyL.A total of 98 patients who underwent 18F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUVmax), and maximum standardized uptake value corrected to lean body mass (SULmax) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUVmax and SULmax values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean).Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated 18F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts.As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of 18F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.
Keywords: 18F-DCFPyL; Imaging pitfalls; Prostate cancer; PSMA; Ganglia

Myocardial perfusion single photon emission computed tomography (SPECT) is often performed even in patients with chronic kidney disease (CKD). We assessed the effects of CKD on myocardial washout rate (WR) of thallium (Tl)-201 in patients with normal myocardial perfusion on SPECT.Two hundred and fifty-six patients with normal myocardial perfusion were enrolled in this study. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Patients with eGFR ≥ 60 ml/min/1.73 m2 were assigned to a control group. The mean myocardial WR of Tl-201 was calculated from the stress and the redistribution Bull’s eye maps.With progressive CKD stages, systolic blood pressure and incindence of hypertension were increased. All patients in CKD stage 5 group were being treated with hemodialysis. Myocardial WR of Tl-201 was significantly higher in all of the CKD groups than control group. With progressive CKD stages, myocardial WR of Tl-201 was increased (stage 3, 52.2 ± 9.2%; stage 4, 55.5 ± 8.1%; and stage 5, 58.9 ± 5.6%). Multivariate analysis showed that hemoglobin (β = −0.24, p < 0.001) and eGFR (β = −0.24, p = 0.002) were the major determinants of myocardial WR of Tl-201, but hemodialysis was not.Our data suggest that CKD is associated with increased myocardial WR of Tl-201 in patients with normal perfusion on SPECT.
Keywords: Thallium; Perfusion; Myocardium; Renal function

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer by Yasemin Sanli; Serkan Kuyumcu; Oner Sanli; Fikret Buyukkaya; Ayça İribaş; Goksel Alcin; Emin Darendeliler; Yasemin Ozluk; Sevda Ozel Yildiz; Cüneyt Turkmen (709-717).
To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga68-PSMA PET/CT in patients with recurrent PCa.A total of 109 consecutive patients (median age 71 years; range 48–89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented.In 91(83.4%) patients at least one lesion characteristic for PCa was detected by68Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2–640) ng/ml.There was a significant difference between 68Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911–0.993). 68Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68Ga-PSMA PET/CT results.
Keywords: 68Ga-PSMA; Recurrent prostate cancer; PSA value; Gleason score