18F-FDG PET/CT in hepatocellular carcinoma: detection of bone metastasis and prediction of prognosis

Seo, Hyo Jung,Kim, Gun Min,Kim, Joo Hoon,Kang, Won Jun,Choi, Hye Jin Chapman and Hall in association with the British N 2015 Nuclear medicine communications Vol.36 No.3

<P>Objective The purpose of this study was to assess the diagnostic accuracy and prognostic value of F-18-fluorodeoxyglucose PET/computed tomography (CT) in bone metastases from hepatocellular carcinoma (HCC). Patients and methods Of 3912 consecutive HCC patients, 67 patients who had undergone both PET/CT and bone scintigraphy (BS) within a 3-month interval were evaluated. Results Bone metastases were most frequently found in the pelvis (20%), followed by the lumbar spine (14%) and long bones (13%). PET/CT was significantly more sensitive than BS in region-based analyses, with 273 confirmed bone metastases (96.7 vs. 52.7%, respectively; P< 0.001), and in patient-based analyses (99 vs. 85%; P= 0.042). The median survival period was 5 (range, 0.4-18) months. On univariate analysis, poor prognostic factors included age (< 60 years), multiple bone metastases, lymph node metastasis, high serum a-fetoprotein (>= 400 IU/ml), Child-Pugh class B, and high maximum standardized uptake value (SUVmax) of bone metastasis (> 5.0). Large metabolic volume (>= 200 cm(3)) of bone metastasis was another poor prognostic factor. On Cox regression analysis, high a-fetoprotein was the only poor prognostic factor with statistical significance. Conclusion PET/CT was more sensitive than BS in bone metastasis from HCC by both patient-based and region-based analyses, and offered additional information on survival. PET/CT can be helpful in early diagnosis and opportune treatment of bone metastasis from HCC. Copyright (c) 2015 Wolters Kluwer Health, Inc. All rights reserved.</P>

The effect of recombinant human thyroid stimulating hormone on sustaining liver and renal function in thyroid cancer patients during radioactive iodine therapy

Lee, Soo Jin,Lee, Ho-Young,Lee, Won Woo,Kim, Sang Eun Chapman and Hall in association with the British N 2014 Nuclear medicine communications Vol.35 No.7

OBJECTIVE: The aim of this study was to evaluate the effect of recombinant human thyroid stimulating hormone (rhTSH) on sustaining liver and renal function in thyroid cancer patients during radioiodine therapy (RIT). PATIENTS AND METHODS: This study was conducted as a retrospective investigation between January 2005 and April 2012. Ninety-eight thyroid cancer patients who were treated with RIT using both thyroid hormone withdrawal (THW) and rhTSH were enrolled. The levels of cholesterol, aspartate aminotransaminase (AST), alanine transaminase (ALT), and serum creatinine (Cr) were analyzed before and after each RIT. RESULTS: The cholesterol level before RIT with rhTSH was significantly lower than that after RIT with rhTSH (P<0.001). The cholesterol level increased before RIT with THW and decreased to within a normal range after RIT with THW (P<0.001). AST and ALT levels before RIT with THW were significantly higher than those before RIT with rhTSH (P<0.001). The serum Cr level before RIT with THW was higher than that before RIT with rhTSH (P<0.001). No significant differences in the serum values of AST, ALT, and Cr after RIT were observed between the THW and rhTSH groups. The remaining iodine was used to estimate radioiodine clearance and renal function indirectly. In 72 patients treated with the same activity of I for THW and rhTSH, the mean counts of regions of interest in the rhTSH group were significantly lower than those in the THW group (P<0.001). CONCLUSION: rhTSH administration can sustain liver and renal function in thyroid cancer patients during RIT. Moreover, the use of rhTSH reduces unnecessary radiation exposure.

Hybrid lymph node imaging using 64Cu-labeled mannose-conjugated human serum albumin with and without indocyanine green

Kang, Choong Mo,An, Gwang Il,Choe, Yearn Seong Chapman and Hall in association with the British N 2015 Nuclear medicine communications Vol.36 No.10

OBJECTIVE: Human serum albumin (HSA), which has 58 Lys residues, one Cys residue, and indocyanine green (ICG) adsorption sites, can be used as a multifunctional platform for the development of hybrid imaging probes. In this study, we prepared Cu-labeled mannose-conjugated HSA with and without ICG ([Cu]1-ICG and [Cu]1, respectively) and compared hybrid PET/near-infrared fluorescence (NIRF) imaging with positron emission tomography (PET)/Cerenkov luminescence (CL) imaging of lymph nodes (LNs). MATERIALS AND METHODS: 1,4,7,10-Tetraazacyclododecane-N,N&vprime;,N&vprime;&vprime;,N&vprime;&vprime;&vprime;-tetraacetic acid (DOTA)/mannose-conjugated HSA (1) was synthesized by conjugating mannose molecules to Lys residues and a DOTA molecule to a Cys residue of HSA. Compound 1 was then labeled with Cu ([Cu]1), and the resulting [Cu]1 was adsorbed with ICG ([Cu]1-ICG). PET/NIRF or PET/CL imaging and subsequent biodistribution studies were performed in ICR mice after injection of the probes into the foot pads. RESULTS: The numbers of mannose and DOTA molecules conjugated to HSA were 7.17±0.49 and 0.95±0.18, respectively. The site-specific conjugation of one DOTA molecule to HSA was sufficient for Cu-labeling with high efficiency (96.0±1.1%). PET/NIRF and PET/CL imaging and subsequent biodistribution studies demonstrated that the probes were avidly taken up by the popliteal LNs (PO), with a slightly higher uptake ratio of the PO to the lumbar LNs by [Cu]1. CONCLUSION: In-vivo studies suggest that [Cu]1 has more specific and selective binding to mannose receptors in the PO than [Cu]1-ICG.

Radiosynthesis and evaluation of 18F-labeled aliphatic phosphonium cations as a myocardial imaging agent for positron emission tomography

Kim, Dong-Yeon,Kim, Hyeon Sik,Min, Jung-Joon Chapman and Hall in association with the British N 2015 Nuclear medicine communications Vol.36 No.7

INTRODUCTION: Lipophilic cations such as phosphonium cations penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in the mitochondria in response to negative inner-transmembrane potentials. The present study reports the radiosynthesis and evaluation of F-labeled aliphatic triphenylphosphonium cations as a potential agent for myocardial imaging by using PET. MATERIALS AND METHODS: (7-[F]fluoroheptyl)triphenylphosphonium salt ([F]3) and (8-[F]fluorooctyl)triphenylphosphonium salt ([F]6) were radiolabeled by means of two-step nucleophilic substitution reactions. We measured the log P value of [F]3 and [F]6 to assess the appropriate range of lipophilicity for their suitability as PET myocardial imaging agents. Normal rats were imaged with microPET after intravenous injection of 37 MBq of [F]3 and [F]6. To determine the pharmacokinetics, a region of interest was drawn around the heart, and time–activity curves of [F]3 and [F]6 were generated to obtain the counts per pixel per second. RESULTS: The radiolabeled compounds [F]3 and [F]6 were synthesized with 18–25% yield. The radiochemical purity was greater than 98% on the basis of the analytical high-performance liquid chromatography system, and the specific activity was greater than 160–170 Ci/mmol. The log P value of the tracers was 2.52±0.01 ([F]3) and 2.91±0.02 ([F]6). Myocardium-to-liver ratios of [F]3 and [F]6 were 2.59 and 1.07, respectively, 10 min after injection, whereas the myocardium-to-lung ratios were 5.57 and 3.35, respectively. In addition, [F]3 and [F]6 showed intense, homogenous uptake in the myocardium. CONCLUSION: F-labeled aliphatic phosphonium cations [F]3 and [F]6 might have potential as novel myocardial agents for PET and could prove useful in clinical cardiac PET/computed tomography applications.

Incidental thyroid cancer detected by 18F-FDG PET: does it have different clinicopathological features?

Pak, Kyoungjune,Cheon, Gi Jeong,Lee, Kyu Eun,Park, Young Joo,Choi, Hoon Sung,Min, Hye Sook,Kang, Keon Wook,Chung, June-Key,Kim, Euishin E.,Lee, Dong Soo Chapman and Hall in association with the British N 2014 Nuclear medicine communications Vol.35 No.5

<P>ObjectivesThe prevalence and risk of malignancy in thyroid incidentalomas has been investigated in previous studies; however, these studies have not looked at the characteristics of incidental thyroid cancer (ITC) detected by fluorine-18 fluorodeoxyglucose PET. Therefore, we aimed to assess the clinicopathologic features of ITC.MethodsFrom March 2008 to December 2011, a total of 2892 patients underwent total thyroidectomy for papillary thyroid cancer. Among them, patients belonging to the ITC group were defined as those in whom focal thyroid uptake was reported as an incidental finding on PET imaging and further evaluation revealed the presence of malignancy. In addition, two control groups with non-PET incidental thyroid cancer (NITC) were selected: NITC-A patients (n=48) who underwent a total thyroidectomy in March 2008 and NITC-B patients (n=48) who underwent a total thyroidectomy for papillary thyroid cancer and were matched for the confounding effects of age and sex.ResultsThere were no significant differences in clinicopathologic features, except for age and tumour node metastasis (TNM) staging, between ITC and NITC-A patients. More ITC than NITC-A patients were aged 45 years or older. Although T, N, or M staging was not different between ITC and NITC-A, there were more ITC patients with stage III/IV tumours. After matching for age and sex, none of the clinicopathologic features showed significant differences between ITC and NITC-B patients.ConclusionNo significant differences were observed between ITC and NITC patients except for age and TNM staging. More ITC patients had advanced TNM stage most likely due to patient age.</P>

In-house development of an optimized synthetic module for routine [ ¹¹ C]acetate production

Jang, Hwa Youn,Kwon, Seong Young,Pyo, Ayoung,Hur, Min Goo,Kim, Sang Wook,Park, Jeong-Hoon,Kim, Hee-Jung,Yang, Seung Dae,Lee, Sunwoo,Kim, Dong-Yeon,Min, Jung-Joon Chapman and Hall in association with the British N 2015 Nuclear medicine communications Vol.36 No.1

<▼1><P>Supplemental Digital Content is available in the text.</P></▼1><▼2><P>[<SUP>11</SUP>C]Acetate, a radiotracer for PET imaging, is a promising radiopharmaceutical for overcoming the limitation of 2-deoxy-2-[<SUP>18</SUP>F]fluoro-<SMALL>D</SMALL>-glucose in a number of cancers. Here, the optimized automatic synthesis of [<SUP>11</SUP>C]acetate using an in-house-developed module under different conditions has been reported for routine production. [<SUP>11</SUP>C]CO<SUB>2</SUB> was produced in a 16.4 MeV PETtrace cyclotron, and methyl magnesium chloride was used for synthesis. For product purification, ion-exchange solid-phase extraction cartridges were used, connected in series. High-performance liquid chromatography and gas chromatography were used to measure radiochemical and chemical purity. The Limulus amebocyte lysate test and the fluid thioglycollate medium test were performed for quality control of [<SUP>11</SUP>C]acetate. The total reaction time of [<SUP>11</SUP>C]acetate was within 15 min, and the overall decay-corrected radiochemical yield was 84.33±8.85%. Radiochemical purity was greater than 98% when evaluated on an analytical high-performance liquid chromatography system. No endotoxins or anaerobic bacteria were seen on quality control checks. Optimized production of [<SUP>11</SUP>C]acetate was achieved by the in-house module. Radiochemical and biological properties of the [<SUP>11</SUP>C]acetate produced were appropriate for clinical PET study.</P></▼2>

Meta-analysis of meta-analyses in oncologic positron emission tomography

Pak, Kyoungjune,Shin, Seunghyeon,Kim, So Jung,Kim, Keunyoung,Seo, Youngduk,Kim, Seong-Jang,Kim, In Joo Chapman and Hall in association with the British N 2018 Nuclear medicine communications Vol.39 No.12

OBJECTIVES: As PET has become a standard of treatment in patients with cancer, publications of oncologic PET have grown sharply. We aimed to organize the data of meta-analyses of oncologic PET and assess the quality of studies. MATERIALS AND METHODS: The inclusion criteria were studies that meta-analyzed to combine the data from multiple studies of oncologic PET. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) to assess the reporting quality of the included studies. RESULTS: A total of 254 meta-analyses were eligible for inclusion in the study. The peak number of publications increased up to 42 in 2014. Lung (n=39, 15.4%) is the most common site of tumor included in meta-analysis with oncologic PET. Overall, 84% of studies were categorized into diagnostic test accuracy reviews (n=214). Studies published in 2010 or later (n=213) showed higher PRISMA scores than those published in 2009 or before. CONCLUSION: A large number of meta-analyses are published in the field of oncologic PET. Meta-analyses in oncologic PET seem to be cited more often than regular research papers. The overall quality of studies is low; however, they showed improvement after PRISMA statement.

The clinical significance of technetium-99m methylene diphosphonate bone scintigraphy findings in patients with rhabdomyolysis

Lee, Jeong Won,Lee, Eun-Young,Hong, Sae-Yong,Yoo, Ik Dong,Lee, Sang Mi Chapman and Hall in association with the British N 2017 Nuclear medicine communications Vol.38 No.10

OBJECTIVE: This study evaluated the relationship between bone scintigraphy finding and clinical factors and assessed the prognostic value of bone scintigraphy finding in patients with rhabdomyolysis. PATIENTS AND METHODS: We retrospectively enrolled 143 patients with rhabdomyolysis who had undergone bone scintigraphy. Bone scintigraphy was classified into three groups: no or equivocal soft tissue uptake, a localized uptake, and a diffuse uptake. The relationship of bone scintigraphy findings with clinical factors was evaluated. Multiple logistic regression analysis was performed to identify the risk factors for acute renal failure (ARF) and renal replacement therapy (RRT). RESULTS: Of 143 patients, 52 (36.4%) experienced ARF and 12 (8.4%) required RRT. Among cases caused by exercise, 83.7% showed localized soft tissue uptake. Diffuse soft tissue uptake was only shown among the patients with rhabdomyolysis caused by drug and toxin. Patients with localized or diffuse soft tissue uptake had higher levels of serum creatine kinase, myoglobin, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase compared with patients with no or equivocal uptake (P<0.05). Multiple logistic regression analysis showed that age, female sex, and serum phosphate level were associated with a risk for ARF and only serum creatinine level was associated with a risk for RRT (P<0.05). Bone scintigraphy findings failed to show significance for predicting ARF and RRT (P>0.05). CONCLUSION: Soft tissue uptake on bone scintigraphy in patients with rhabdomyolysis was related to etiologies and showed limited value for predicting ARF and RRT.

The value of brain perfusion SPECT for differentiation between mildly symptomatic idiopathic Parkinson’s disease and the Parkinson variant of multiple system atrophy

Song, In-Uk,Yoo, Ikdong,Chung, Yong-An,Jeong, Jaeseung Chapman and Hall in association with the British N 2015 Nuclear medicine communications Vol.36 No.10

INTRODUCTION: Brain perfusion deficits have been reported previously in patients with Parkinson’s disease (PD) and multiple system atrophy (MSA). However, clinical differential diagnosis between mildly symptomatic PD and the Parkinson’s variant of MSA (MSA-P) is difficult because of the similarity of symptoms between parkinsonian disorders. Accurate diagnosis of these disorders is important for treatment decisions, appropriate advice, management, and prognosis. Therefore, we conducted this study to investigate the difference in perfusion single-photon emission computed tomography (SPECT) between patients with mild symptomatology of PD and those with MSA-P using the SPM program. PATIENTS AND METHODS: We consecutively recruited 47 patients with PD, 21 patients with MSA-P, and 48 age-matched healthy controls. All participants underwent Tc-99m hexamethylpropyleneamine oxime (HMPAO) perfusion SPECT, and the perfusion images were analyzed. RESULTS: Perfusion SPECT showed hypoperfusion in the frontal cortex in both PD and MSA-P patients compared with healthy controls. Hypoperfusion in the occipital cortex was seen only in PD patients. There are no significant intercorrelations of blood flow in the cerebral region between PD and MSA-P patients. CONCLUSION: We cautiously assume that the only difference in cerebral blood perfusion images of mild symptomatic PD and MSA-P patients is blood perfusion in the occipital cortex. Although there are many cerebral regions with similar perfusion in patients with PD and MSA-P of mild symptomatology, we could assume that each has a completely different pathophysiology for PD and MSA-P because of the lack of significant intercorrelation of blood flow in the cerebral region.

Prognostic implication of retrocrural lymph node involvement revealed by 18F-FDG PET/CT in patients with uterine cervical cancer

Im, Hyung-Jun,Yoon, Hai-Jeon,Lee, Eun Seong,Kim, Tae-Sung,Kim, Joo-Young,Chung, June-Key,Kim, Seok-ki,Park, Sang-Yoon Chapman and Hall in association with the British N 2014 Nuclear medicine communications Vol.35 No.3

OBJECTIVES: Lymph node involvement in cervical cancer is an indication of poor prognosis and the risk tends to increase according to the level of lymph node involvement. However, the specific prognostic significance of retrocrural lymph node involvement has not been well characterized because of its small size and deep location. The aim of this study was to assess its prognostic value. PATIENTS AND METHODS: A total of 217 patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IA2–IVA cervical cancer were retrospectively enrolled. All the patients had undergone pretreatment F-fluorodeoxy-D-glucose (F-FDG) PET/CT. Of these patients 145 were treated with concurrent chemoradiotherapy, and in this group we assessed the relationship of retrocrural lymph node involvement with the risk of disease progression. RESULTS: Retrocrural lymph node involvement was seen in 7.4% of patients (16/217). All of them had para-aortic lymph node involvement and 56% of the 16 patients (9/16) had concomitant supraclavicular lymph node involvement. In the patients treated with concurrent chemoradiotherapy it was found that the higher the level of F-FDG-positive lymph nodes detected in them, the worse the progression-free survival experienced by them (none vs. pelvic, pelvic vs. para-aortic, para-aortic vs. retrocrural; P<0.05); however, there was no difference in progression outcome between retrocrural and supraclavicular areas (P=NS). On multivariate Cox proportional hazard analysis, the highest level of F-FDG PET/CT-positive lymph nodes in the para-aortic [hazard ratio (HR) 6.05, 95% confidence interval (CI) 2.18–16.81], retrocrural (HR 17.05, 95% CI 5.34–54.44), and supraclavicular areas (HR 19.56, 95% CI 7.15–53.54) was a significant prognostic factor. CONCLUSION: The highest level of lymph node involvement in para-aortic, retrocrural, supraclavicular areas was a significant prognostic factor for progression in uterine cervical cancer patients who were treated with concurrent chemoradiotherapy. Retrocrural lymph node involvement shows a similar outcome with supraclavicular involvement, but leads to a worse outcome in terms of progression compared with para-aortic lymph node involvement.