Annals of Nuclear Medicine (v.31, #5)

Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study by Jolanta Kunikowska; Dariusz Pawlak; Marianna I. Bąk; Beata Kos-Kudła; Renata Mikołajczak; Leszek Królicki (347-356).
The peptide receptor radionuclide therapy (PRRT) with 90Y and 177Lu is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET).The aim of the study was to evaluate clinical results and long-term side effects of tandem 90Y /177Lu-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site.59 patients with disseminated NET were included in the study prospectively. 3–5 cycles of combined 1:1 90Y/177Lu-DOTATATE (total injected activity 11.1–16.65 GBq) with mixed amino acids for kidney protection were performed.During a median follow-up of 75.8 months, the PFS was 32.2 months, and the OS was 82 months; 25 patients died. Depending on primary tumor’s site, the PFS and the OS for pancreatic NET vs. small bowel, NET vs. large bowel, NET were 30.4 vs. 29.5 vs. 40.3 and 78.9 vs. 58.1 vs. 82.5, respectively. The observed 5-year overall survival was 63%, and a 2-year risk of progression was 39.4%. The following imaging response was observed: CR in 2%, PR in 22%, SD in 65%, and PD in 6% patients. The disease control rate was 89%. The objective response rate was 24%. The PRRT was well tolerated by all patients. One patient (2%) revealed MDS, and one patient (2%) grade 3 nephrotoxicity. No other grade 3 and 4 hematological or renal toxicity was observed.These results indicated the tandem 90Y/177Lu-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.
Keywords: PRRT; 90Y/177Lu-DOTATATE; Tandem therapy; Somatostatin receptor; Neuroendocrine tumors.

Compared to 123I-MIBG SPECT/CT, 18F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma by Alexander Stephan Kroiss; Christian Uprimny; Barry Lynn Shulkin; Andreas Frech; Herbert Tilg; Rudolf Wolfgang Gasser; Georg Mathias Sprinzl; Leonhard Gruber; Claudius Thomé; Clemens Plangger; Christoph Url; Gustav Fraedrich; Irene Johanna Virgolini (357-365).
The aim of this study was to compare the accuracy of 123I-MIBG SPECT/CT with that of 18F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards.Three men and seven women (age range 26–73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with 18F-DOPA PET, and 123I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis.On a per-patient basis, 18F-DOPA PET’s detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar 123I-MIBG imaging alone was 10.0% and that of 123I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, 18F-DOPA PET showed a sensitivity of 69.2% (McNemar p < 0.001) compared with anatomical imaging. Sensitivity of planar 123I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p < 0.0001). Overall, 18F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar 123IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions. 18F-DOPA PET is more sensitive than is 123I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.
Keywords: 123I-MIBG; 18F-DOPA; PET/CT; Extra-adrenal paraganglioma

The aim of this study was to systematically review the literature to evaluate the clinical performance of integrated 18F-FDG PET/MR as compared with 18F-FDG PET/CT in oncologic imaging.The literature was searched using MEDLINE and EMBASE via OVID. Studies comparing the diagnostic accuracy of integrated 18F-FDG PET/MR and 18F-FDG PET/CT in the diagnosis, staging/restaging, assessment of treatment response, or evaluation of metastasis in patients with suspected or diagnosed cancers were deemed eligible for inclusion. Risk of bias and applicability concerns were assessed using the QUADAS-2 tool.Twenty studies met the inclusion criteria. The overall quality of the studies was rated favorably with bias or applicability concerns in a few studies. Our review suggests that 18F-FDG PET/MR performs comparably to 18F-FDG PET/CT in the detection of local lymph node and distant metastases and superiorly in determining the local extent of tumor. SUV obtained from 18F-FDG PET/MR correlated highly with those obtained from 18F-FDG PET/CT.Based on early evidence, 18F-FDG PET/MR is comparable to 18F-FDG PET/CT in the clinical scenarios examined in this review. The potential for interchangeability of 18F-FDG PET/MR with 18F-FDG PET/CT will vary by indication and the body site that is being imaged, with PET scanners integrated with MRI predicted to provide greater detail in the evaluation of local tumor extent, where 18F-FDG PET/CT can be limited.
Keywords: FDG; PET/MR; PET/CT; Multimodal imaging; Oncology

Survival and prognostic factors after adjuvant 131iodine-labeled lipiodol for hepatocellular carcinoma: a retrospective analysis of 106 patients over 20 years by Jonathan Olesinski; François Mithieux; Olivier Guillaud; Marie-Noëlle Hilleret; Catherine Lombard-Bohas; Luc Henry; Olivier Boillot; Thomas Walter; Christian Partensky; Pierre Paliard; Pierre-Jean Valette; Jean-Philippe Vuillez; Françoise Borson-Chazot; Jean-Yves Scoazec; Jérôme Dumortier (379-389).
Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of 131I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up.All patients treated with 131I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study.One hundred and six patients were included. The median (range) follow-up was 6 years (0.3–22). Forty-three patients (41%) had cirrhosis. Recurrence-free survival rates at 1, 2, 5, 10, and 20 years were 73, 57, 40, 30, and 14%, respectively. Cirrhosis was an independent predictive factor of recurrence [RR = 1.18, 95% CI (1.11–3.02), p = 0.019]. Overall, survival rates at 1, 2, 5, 10, and 20 years were 90, 83, 59, 37, and 23%, respectively. Prognostic factors were recurrence [RR = 2.73, 95% CI (1.35–5.54); p = 0.005], age over 60 years (RR = 1.91, 95% CI [1.02–3.61]; p = 0.044), and tumor number over 3 [RR = 3.31, 95% CI (1.25–8.77); p = 0.016].Our results suggest that the effect of 131I-lipiodol after curative treatment of HCC could be related to a beneficial impact on risk factors of early tumor recurrence. This could be evaluated in further studies using modern radioembolization methods.
Keywords: Hepatocellular carcinoma; Adjuvant therapy; Iodine-lipiodol, survival.

Correlation between clinical symptoms and striatal DAT uptake in patients with DLB by Soichiro Shimizu; Disuke Hirose; Nayuta Namioka; Hidekazu Kanetaka; Kentaro Hirao; Hirokuni Hatanaka; Naoto Takenoshita; Yoshitsugu Kaneko; Yusuke Ogawa; Takahiko Umahara; Hirofumi Sakurai; Haruo Hanyu (390-398).
It is widely known that there is low striatal 123I-FP-CIT dopamine transporter-single photon emission tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). We assessed the correlation between symptom and regional low DAT uptake in the striatum.Patients with Alzheimer’s disease (AD) (n = 95) and patients with DLB (n = 133) who underwent DAT-SPECT were enrolled. We examined the correlation between symptoms [cognitive function decline, fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder (RBD)] and regional striatal DAT uptake in the patients with DLB.When comparing the DLB patients with or without fluctuations, visual hallucinations, or RBD, there were no significant differences in DAT uptake in any regions of the striatum. DLB patients with parkinsonism had significantly lower DAT uptake in entire striatum, entire putamen, and anterior putamen compared to DLB patients without parkinsonism. Moreover, there was weak but significant correlation between severity of parkinsonism and DAT uptake in entire regions of the striatum in patients with DLB. There was no significant correlation between cognitive function and DAT uptake in any regions of the striatum in patients with DLB.In patients with DLB, only parkinsonism is associated with a reduction in striatal DAT uptake.
Keywords: Dementia with Lewy bodies; Parkinsonism; 123I-FP-CIT; DAT scan; Alzheimer’s disease

Incidental spade-shaped FDG uptake in the left ventricular apex suggests apical hypertrophic cardiomyopathy by Mari Katagiri; Tadaki Nakahara; Mitsushige Murata; Yuji Ogata; Yohji Matsusaka; Yu Iwabuchi; Yoshitake Yamada; Keiichi Fukuda; Masahiro Jinzaki (399-406).
Apical wall thickening with an “ace-of-spades” configuration is a unique sign of apical hypertrophic cardiomyopathy (AHCM). We investigated spade-shaped FDG uptake around the left ventricular apex (SSUA) incidentally found in routine oncological FDG PET.Cases showing SSUA were selected based on retrospective review. The pattern or intensity of SSUA was compared with the results of electrocardiogram (ECG), echocardiography, and stress myocardial perfusion SPECT. The diagnosis of ACHM was based on the presence of giant negative T wave in ECG, thickness of spade-shaped hypertrophy in the apex in echocardiography, and increased tracer uptake in the apex in rest SPECT.Among the 34 patients in 36 PET scans showing SSUA, SSUA was weak in 17 and intense in 17. There were isolated SSUA (n = 29) and SSUA with diffuse or other focal left ventricular uptake (n = 5). Three patients with the latter uptake pattern turned out to have coexistence of AHCM and asymmetric septal hypertrophy. Of the 16 SSUA-positive patients who underwent echocardiography, 13 (81%) were diagnosed as AHCM and the remaining 3 were regarded as borderline AHCM (apical wall thickness, 14–15 mm). There were 16 patients with SSUA who also underwent PET scans after the study period among which 11 (69%) had persistent SSUA in the follow-up PET. In the remaining 5, follow-up PET scans showed diffuse left ventricular uptake and SSUA was barely visible. The intensity of SSUA was significantly or marginally associated with giant negative T wave (p < 0.01), apical asynergy (p = 0.08), and impaired coronary flow reserve (p < 0.05). There were no other factors correlated with the pattern or intensity of SSUA.SSUA incidentally found in oncological FDG PET appeared to be associated with AHCM, especially in ischemic conditions. The moderate repeatability of SSUA was probably due to obscurity by physiological uptake.
Keywords: Hypertrophic cardiomyopathy; Apical hypertrophy; FDG PET; Electrocardiogram; Echocardiography; Perfusion SPECT

Age-related effects and gender differences in Japanese healthy controls for [123I] FP-CIT SPECT by Hideo Yamamoto; Shinichi Arimura; Atsushi Nakanishi; Yasushi Shimo; Yumiko Motoi; Koichi Ishiguro; Koji Murakami; Nobutaka Hattori; Shigeki Aoki (407-412).
Dopamine transporter (DAT) imaging with [123I]FP-CIT (DaTSCAN) is a widely used diagnostic tool for Parkinsonism and dementia. Since it was approved by the Japanese Ministry of Health, Labor, and Welfare in 2013, there have been no articles focusing on a Japanese normal population. The aim of this study was to examine the effect of aging and gender on DAT availability in Japanese people.SPECT imaging of 30 healthy Japanese controls (17 males, 13 females; range 50–86 years, mean 70 years) was performed. SPECT images were reconstructed using a three-dimensional order subset expectation maximization (OSEM) algorithm with correction of the point spread function and scatter correction, without attenuation correction. The specific binding ratio (SBR) was calculated by DATview software. Statistical analyses were performed using linear regression analysis, analysis of variance, and multiple comparison analysis.A strong correlation between the SBR and age was observed. The correlation coefficient in males and females were −0.566 and −0.502, respectively. The analysis of variance revealed that aging led to a decline of the SBR, and a significant difference (p = 0.005) was observed among generations. Gender also affected the SBR, and there was a significant difference between males and females (p = 0.036). The SBR in females was higher than in males. Consequently, the multiple comparison revealed a significant difference between 50s and 70s (p = 0.015) and 50s and 80s (p = 0.006).This is the first [123I]FP-CIT SPECT study on subjects with normal dopamine function in Asian countries. This study provides a database of [123I]FP-CIT SPECT in Japanese healthy controls. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 8.9% was found in both genders. The data collected in this study would be helpful for Japanese physicians to make a differential diagnosis in Parkinsonian syndrome.The registration identification number for this study is UMIN000018045.
Keywords: [123I]FP-CIT SPECT; Japan; Normal database; Dopamine transporter

Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models: evaluation of insulin and β3-adrenergic receptor agonist effects by 18F-FDG by Seigo Ishino; Taku Sugita; Yusuke Kondo; Mika Okai; Kazue Tsuchimori; Masanori Watanabe; Ikuo Mori; Masaki Hosoya; Takashi Horiguchi; Hidenori Kamiguchi (413-423).
One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals.A radiotracer for glucose, 18F-2-deoxy-2-fluoro-d-glucose (18F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316,243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. 18F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography.In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin, while the responses were inhibited in the adipose tissues of Wistar fatty rats.A system to monitor tissue glucose uptake with 18F-FDG enabled us to detect clear differences in basal glucose uptake between disease-model animals and their corresponding controls. The responses in the tissues to insulin or β3 agonist could be identified. Taken as a whole, the biodistribution method with 18F-FDG was confirmed to be useful for pharmacological evaluation of anti-diabetic or anti-obesity drugs using disease-model animals.
Keywords: 18F-FDG; Wistar fatty rat; DIO mouse; Insulin; β3 agonist