Annals of Nuclear Medicine (v.30, #8)

18F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes by Dalton A. dos Anjos; Angelita Habr-Gama; Bruna B. Vailati; Cecilia B. Rossi; Adelina E. Coturel; Rodrigo O. Perez; Guilherme P. São Julião; João B. de Sousa; Carlos A. Buchpiguel (513-517).
PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low 18F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.
Keywords: 18F-FDG PET/CT; Rectal cancer; Mucinous adenocarcinoma

Impact of patient age on the iodine/FDG “flip-flop” phenomenon in lung metastasis from thyroid cancer by Takuro Isoda; Shingo BaBa; Yasuhiro Maruoka; Yoshiyuki Kitamura; Keiichiro Tahara; Masayuki Sasaki; Hiroshi Honda (518-524).
Radioiodine therapy is an effective treatment for lung metastasis from thyroid cancer. However, cases of lung metastasis without iodine uptake are often encountered. In such cases, FDG accumulation in lung lesions is often observed. There is a reverse relationship between iodine and FDG accumulation in thyroid cancer lesions, the so-called “flip-flop” phenomenon. The aim of this study was to assess the relationship between patient age and the occurrence of the flip-flop phenomenon.Eighty-six patients who underwent radioiodine therapy for lung metastasis were studied retrospectively (age 17–73 years; median 60 years; males:females 22:64). We compared the clinical data and imaging findings (size and FDG uptake of lung nodules) between patients with (n = 44) and without (n = 42) iodine uptake in lung metastasis.Significantly more young patients showed iodine accumulation in lung metastasis than old patients (p = 0.0025). Lung metastases with larger size or greater FDG uptake showed no iodine uptake more frequently with significant difference (p = 0.015 and <0.001, respectively). Among patients with FDG uptake in the lung metastasis, 57.1 % of young patients (<60 years) and 24.3 % of the old patients (≥60 years) showed iodine uptake (p = 0.0029).Higher patient age and lung nodules with large size or FDG accumulation are negative factors for iodine accumulation in lung metastases from thyroid cancer. In addition, our results show that young patients have a greater likelihood of iodine uptake even when FDG accumulates in lung metastasis, in contrast to old patients.
Keywords: Thyroid cancer; Radioiodine therapy; Flip-flop phenomenon; FDG-PET

The present study aimed to investigate the effect of 18F-fluorodeoxyglucose (FDG) extravasation on the time taken for tumoral uptake to reach a plateau.For the animal experiment, FDG extravasation was conducted in the tails of HCT116 tumor-bearing xenograft mice models in three groups (no extravasation, 40 % extravasation, and 80 % extravasation; n = 5, each). Dynamic positron emission tomography (PET) images were acquired over a period of 2 h following injection. Time–activity curves for FDG in the tails and tumors were calculated. For the clinical experiment, 22 patients (male:female, 14:8; age range, 70.8 ± 9.2 years) were subjected to PET/computed tomography (PET/CT) 1 h after the injection of FDG. The inclusion criteria were as follows: (1) submitted to both whole-body and subsequent regional scanning; (2) entire extravasation activity visualized in the whole-body images; (3) tumor visualized on both whole-body and additional regional images; and (4) status of tumor either confirmed by biopsy or clinically suspected for malignancy. The standardized uptake values (SUVs) of the tumors (on the whole-body and additional PET images) and extravasation sites were recorded.There were no significant differences in the time taken for tumoral uptake to reach a plateau and that to reach minimum activity at the extravasation site among the three groups of mice. However, the mean tumoral activity and activity at the extravasation site were negatively correlated at 1 h post-injection. According to the clinical PET findings, the differences in SUV between the whole-body and regional images were not significantly correlated with the interval between injection of FDG and start of whole-body scanning, interval between the start of whole-body scanning and start of regional scanning, extravasation volume, maximum SUV of the extravasation site, or total activity at the extravasation site.The time taken for tumoral uptake to reach a plateau is not affected by extravasation, even at extensive degrees. Thus, in routine practice, the imaging time of approximately 60 min post-injection need not be modified even if extravasation is identified. However, tumor SUV may be underestimated in cases of extravasation.
Keywords: Extravasation; Timing; Time–activity curve; Tumor; FDG; PET

Preclinical and first-in-man studies of [11C]CB184 for imaging the 18-kDa translocator protein by positron emission tomography by Jun Toyohara; Muneyuki Sakata; Kentaro Hatano; Shuichi Yanai; Shogo Endo; Kenji Ishibashi; Kei Wagatsuma; Kenji Ishii; Kiichi Ishiwata (534-543).
We performed preclinical and first-in-man clinical positron emission tomography (PET) studies in human brain using N,N-di-n-propyl-2-[2-(4-[11C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([11C]CB184) to image the 18-kDa translocator protein (TSPO), which is overexpressed in activated microglia in neuroinflammatory conditions.In vitro selectivity of CB184 was characterized. The radiation absorbed dose by [11C]CB184 in humans was calculated from murine distribution data. Acute toxicity of CB184 hydrochloride in rats at a dose of 5.81 mg/kg body weight, which is >10,000-fold higher than the clinical equivalent dose of [11C]CB184, was evaluated. Acute toxicity of [11C]CB184 injection of a 400-fold dose to administer a postulated dose of 740 MBq [11C]CB184 was also evaluated after the decay-out of 11C. The mutagenicity of CB184 was studied with a reverse mutation test (Ames test). The pharmacological effect of CB184 injection in mice was studied with an open field test. The first PET imaging of TSPO with [11C]CB184 in a normal human volunteer was performed.A suitable preparation method for [11C]CB184 injection was established. CB184 showed low activity in a 28-standard receptor binding profile. The radiation absorbed dose by [11C]CB184 in humans was sufficiently low for clinical use, and no acute toxicity of CB184 or [11C]CB184 injection was found. No mutagenicity or apparent effect on locomotor activity or anxiety status was observed for CB184. We safely performed brain imaging with PET following administration of [11C]CB184 in a normal human volunteer. A 90-min dynamic scan showed rapid initial uptake of radioactivity in the brain followed by prompt clearance. [11C]CB184 was homogeneously distributed in the gray matter. The total distribution volume of [11C]CB184 was highest in the thalamus followed by the cerebellar cortex and elsewhere. Although regional differences were small, the observed [11C]CB184 binding pattern was consistent with the TSPO distribution in normal human brain. Peripherally, [11C]CB184 was metabolized in humans: 30 % of the radioactivity in plasma was detected as the unchanged form after 60 min.[11C]CB184 is suitable for imaging TSPO in human brain and provides an acceptable radiation dose. Pharmacological safety was noted at the dose required for PET imaging.
Keywords: TSPO; [11C]CB184; Central nervous system; Positron emission tomography

The utility of PET/CT with 68Ga-DOTATOC in sarcoidosis: comparison with 67Ga-scintigraphy by Tomomi Nobashi; Yuji Nakamoto; Takeshi Kubo; Takayoshi Ishimori; Tomohiro Handa; Kiminobu Tanizawa; Kohei Sano; Michiaki Mishima; Kaori Togashi (544-552).
This study was designed to compare the clinical efficacy of 68Ga-DOTA-Tyr-octreotide (DOTATOC)-positron emission tomography (PET)/computed tomography (CT) with that of conventional 67Ga-scintigraphy (GS), and to correlate quantitative parameters on DOTATOC-PET/CT with clinical data, in patients with sarcoidosis.Twenty patients who were histologically and/or clinically diagnosed with sarcoidosis and underwent both DOTATOC-PET/CT and GS were analyzed in this study. The numbers of patients with positive findings for each organ were determined. The total numbers of involved nodal areas in the chest, as determined by DOTATOC-PET and gallium single-photon emission tomography (Ga-SPECT), were compared. The correlations between quantitative parameters on PET and clinical laboratory data were evaluated.DOTATOC-PET/CT was positive in 19 patients, being negative in only one patient with chronic inactive sarcoidosis, whereas GS was positive in 17 patients. DOTATOC-PET/CT visualized more lesions in lymph nodes, uvea, and muscles than did Ga-scintigraphy and identified more involved areas than did GS-SPECT (p < 0.0001). Whole-body active lesion volume showed a significant, but moderate correlation with angiotensin-converting enzyme level (ρ = 0.64, p = 0.0044).PET/CT with DOTATOC may be superior to conventional GS in detecting sarcoidosis lesions, especially in lymph nodes, uvea, and muscles. Volumetric parameters in DOTATOC-PET/CT may be helpful in estimating the activity of sarcoidosis.
Keywords: Sarcoidosis; DOTATOC-PET/CT; Somatostatin receptor scintigraphy; Ga-scintigraphy

11C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with 18F-fluorodeoxyglucose PET by Maya K. Arimoto; Tatsuya Higashi; Ryuichi Nishii; Shinya Kagawa; Masaaki Takahashi; Yoshihiko Kishibe; Hiroshi Yamauchi; Satoshi Ishitoya; Hiroyuki Oonishi; Yuji Nakamoto; Kaori Togashi (553-562).
α-N-methyl-11C-methylaminoisobutyric acid (11C-MeAIB) is a selective substrate of system A amino acid transport, and known to accumulate in malignant lesions. The aim of this study was to evaluate the utility of MeAIB PET for the assessment of prostate cancer, compared with FDG PET.Thirty-four men (age range 57–77 years) with prostate cancer were prospectively enrolled, and underwent MeAIB PET and FDG PET between January 2011 and January 2013. MeAIB PET and FDG PET were performed at 20 and 50 min post-injection, respectively. SUVmax of the prostate was calculated, and visual analysis was conducted for MeAIB and FDG PET studies. MRI images were visually evaluated if available. All patients received total prostatectomy subsequently, and imaging findings were compared with pathological results, including T stage, Gleason score, and tumor size. The patient-based and lesion-based sensitivity and specificity were calculated according to pathological significant cancer.Mean value of SUVmax of 11C-MeAIB PET and 18F-FDG PET in prostate cancer were 3.18 (±1.90, range; 1.55–9.57) and 3.88 (±2.85, range; 2.04–14.47). MeAIB PET and FDG PET were positive by visual analysis in 47.1 % (16/34) and 44.1 % (15/34) of the patients. MRI was positive in 51.5 % (17/33). Pathological stage and Gleason score were as follows: Stage 2 (n = 23), 3 (n = 8), and 4 (n = 3); Gleason score 6 (n = 13), 7 (n = 16), 8 (n = 3), and 9 (n = 2). The sensitivities tended to be higher according to higher pathological T stage or Gleason sum score for both MeAIB and FDG PET studies. Visual analysis of both MeAIB PET and FDG PET had significant correlation with extraprostatic extension (p < 0.05). MeAIB PET and FDG PET had complementary results by visual analysis in the assessment of prostate cancer. The patient-based sensitivity of MeAIB PET, FDG PET, and MRI were 51.6, 48.4, and 56.7 %, respectively. The patient-based specificity of these modalities was 100 % for each modality.MeAIB PET has better diagnostic results than FDG PET for the assessment of significant prostate cancer, and these PET studies showed complementary results. MRI has even better diagnostic results than 11C-MeAIB PET. MeAIB accumulates in prostate cancer, which indicates that the system A amino acid transport pathway is activated in prostate cancer.
Keywords: Methylaminoisobutyric acid; Fluorodeoxyglucose; Prostate cancer; Positron emission tomography

A two‐center study for the quality control of [18F]FDG using FASTlab phosphate cassettes by Ya-Yao Huang; Stephen Taylor; Jacek Koziorowski; Yu-Ning Chang; Wei-Hua Kao; Kai-Yuan Tzen; Chyng-Yann Shiue (563-571).
The GE FASTlab radiosynthesis module is routinely used for the production of [18F]FDG, utilizing the commercially available phosphate cassettes. Because of the observation of a white precipitate in the product vial before the product expiry time, we re-examined the quality of the produced [18F]FDG solution.Phosphate buffered [18F]FDG solution was synthesized on the FASTlab and analyzed at both National Taiwan University Hospital (NTUH) of Taiwan and Royal Brisbane and Women’s Hospital (RBWH) of Australia. In addition to the standard product quality control (QC), the concentration of aluminum (Al3+) as probable cause of the precipitations in the [18F]FDG solution was analyzed by inductively coupled plasma mass spectrometry (ICP-MS at RBWH) and inductively coupled plasma optical emission spectrometry (ICP-OES at NTUH), and using three semi-quantitative methods at NTUH, Advantec® Alumi Check Test Strip, Quantofix® Aluminum Test Strip and MColortest™ Aluminum Test kit.The precipitates were observed in the [18F]FDG solution within 24 (NTUH) and 6 (RBWH) hours after the end of synthesis in 38–100 % of the batches, dependent on the batch of the FASTlab cassettes. Addition of metal-free HCl(aq) to aliquots of [18F]FDG containing precipitate, followed by ICP-MS analysis revealed Al3+ concentrations of 70–80 ppm. Al3+ concentrations of 10–12 ppm were detected in [18F]FDG batches that did not show any precipitation. In contrast, less than 5 ppm of the residual Al3+ was detected by semi-quantitative methods in all batches.The US (USP), British (BP), European (EP) and Japanese (JP) pharmacopeias demand that [18F]FDG for injection should be clear and particulate free within the given shelf-life/expiration time. To avoid Al-phosphate precipitation within the product expiry time, FASTlab citrate cassettes, rather than phosphate cassettes, should be used for [18F]FDG production. Although testing for Al3+ is not listed in the [18F]FDG monographs of the USP, BP and EP, residual Al3+ levels should be considered in the interests of patient safety.
Keywords: [18F]FDG; FASTlab; Phosphate; Cassette; Precipitate

We applied a simple isocontour volume-of-interest (VOI) method to analyze the whole striatum in an F-18 FP-CIT PET image and to investigate the usefulness of the method in differentiating healthy subjects from idiopathic Parkinson’s disease (IPD) patients and the correlation of the value of functional volume parameters with the motor symptoms in patients with IPD.Forty-three IPD patients and 23 age-matched healthy controls underwent F-18 FP-CIT PET. Using a dedicated workstation, VOIs for the whole striatum were drawn automatically with the gradient delineation method. The SUVmax, SUVmean, functional volume (FV), striatal volume activity (SVA), striatal-specific binding (SSB), and volume-specific uptake ratio (VSUR) were compared between the IPD patients and the normal subjects. In the IPD patients, the correlation between the clinical factor and the functional parameters was assessed.The SUVmax, SUVmean, FV, SVA, SSB, and VSUR were significantly lower in the IPD patients than in the normal subjects. In the receiver operating characteristic analysis, those parameters had significant and good-to-excellent accuracy. In the patients with IPD, a moderate negative correlation was revealed between the SUVmax and H&Y stage, the SUVmean and H&Y stage, SVA and H&Y stage, the VSUR and H&Y stage, the FV and bradykinesia, and the SVA and bradykinesia.The functional volumetric analysis of the striatum based on simple isocontour VOI was a useful method of analyzing the F-18 FP-CIT PET image. Not only can it be easily applied in daily clinical practice, but it can also be used as a clinical parameter to discriminate IPD and to correlate it with the disease severity.
Keywords: F-18 FP-CIT; PET; Striatum; Functional volume; Quantification

Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study by Tatsuhiro Terada; Masamichi Yokokura; Etsuji Yoshikawa; Masami Futatsubashi; Satoshi Kono; Takashi Konishi; Hiroaki Miyajima; Takanori Hashizume; Yasuomi Ouchi (579-587).
The neuroinflammatory glial response contributes to the degenerative process in Parkinson’s disease (PD). However, the pattern of microglial progression remains unclear.We evaluated microglial activation in early stage PD patients by quantifying changes in neuroinflammation using PET with [11C]DPA713, a selective PET tracer for microglial activation. Eleven PD patients (Hoehn and Yahr stages 1–2) without dementia underwent the [11C]DPA713 PET scan two times with 1 year apart. The binding potential (BPND) was estimated with the simplified reference tissue model. Voxelwise and regions of interest analyses were used to compare the regional BPND among groups.Significant increase in [11C]DPA713 BPND was found extrastriatally in the occipital, temporal and parietal cortex in PD patients, and the degree of BPND became much higher over the brain regions predominantly in the temporal and occipital cortex 1 year later.The current results indicated that an extrastriatal spreading of microglial activation reflects one of PD pathophysiology occurring at an early stage.
Keywords: Parkinson’s disease (PD); Microglia; [11C]DPA713; Positron emission tomography (PET)

Interim FDG-PET/CT in Hodgkin lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET) by Salvatore Annunziata; Annarosa Cuccaro; Maria Lucia Calcagni; Stefan Hohaus; Alessandro Giordano; Vittoria Rufini (588-592).
To evaluate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with Hodgkin lymphoma (HL) undergoing interim FDG-PET/CT and to compare rPET with the 5-point Deauville Score (5p-DS).Sixty-eight patients with HL undergoing interim FDG-PET/CT after first courses of chemotherapy were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cutpoint of rPET with respect to progression free survival (PFS). The prognostic significance of rPET was compared with 5p-DS (scores 4 and 5 considered as positive). Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of an adverse event as the gold standard.The ROC analysis for rPET as a predictor of progression showed an optimal rPET cutpoint of 1.14. Both 5p-DS and rPET were strong outcome predictors (p < 0.001). Patients with negative 5p-DS and patients with rPET <1.14 had a similar two-year PFS (86 and 87 %, respectively). Patients with a positive 5p-DS had a 2-year PFS of 27 %, while patients with rPET >1.14 had a 2-year PFS of 15 %. 5p-DS and rPET cutoff of 1.14 showed a PPV of 58 versus 70 %, and a NPV of 85 versus 86 %, respectively.rPET could be considered an accurate prognostic factor in patients with HL undergoing interim FDG-PET/CT. Larger prospective studies are needed to confirm these data.
Keywords: Hodgkin; FDG-PET/CT; Deauville; SUVmax; rPET