Annals of Nuclear Medicine (v.29, #10)

18F-FPRGD2 PET/CT imaging of musculoskeletal disorders by Nadia Withofs; Edith Charlier; Paolo Simoni; Victoria Alvarez-Miezentseva; Frédéric Mievis; Fabrice Giacomelli; Christine Mella; Sanjiv S. Gambhir; Olivier Malaise; Dominique de Seny; Michel Malaise; Roland Hustinx (839-847).
This work reports on musculoskeletal uptake of 18F-FPRGD2, targeting the integrin αvβ3, in patients who had undergone 18F-FPRGD2 positron emission tomography combined with computed tomography (PET/CT) for oncologic purposes.Whole-body 18F-FPRGD2 PET/CT images of 62 cancer patients were retrospectively reviewed to detect foci of musculoskeletal 18F-FPRGD2 uptake. For 37 patients, a FDG PET/CT performed in clinical settings was available. In each joint with an abnormal uptake, the maximum standardized uptake value (SUVmax) was estimated.A total of 260 musculoskeletal foci of 18F-FPRGD2 uptake were detected. Most common sites of uptake were joints and discs (n = 160; 61.5 %), entheses (osteotendinous and osteoligamentous junctions; n = 55; 21.2 %) and recent fractures (n = 18; 6.9 %). In addition, 27 (10.4 %) miscellaneous foci were detected. Out of the 146 lesions for which a FDG PET was available, 63 % showed both 18F-FPRGD2 and FDG uptake, 33.6 % did not show FDG avidity and 3.4 % showed only FDG uptake. The uptake intensity of the 92 lesions positive with 18F-FPRGD2 and FDG was similar with both radiopharmaceuticals, but the target-to-background (blood pool or muscle) ratios were significantly higher with 18F-FPRGD2 than with FDG (p < 0.0001).The 18F-FPRGD2 uptake in joints, spine degenerative diseases and tendons was highly prevalent in our population. Up to one-third of 18F-FPRGD2 foci showed no FDG uptake suggesting that 18F-FPRGD2 signal may not be related to inflammatory angiogenesis only.
Keywords: RGD; PET; Integrin; Osteoarthritis; Discopathy; Joint

Concurrent use of strontium-89 with external beam radiotherapy for multiple bone metastases: early experience by Joichi Heianna; Takafumi Toita; Wataru Endo; Goro Kasuya; Takuro Ariga; Seiji Hashimoto; Hitoshi Maemoto; Kazuyuki Terui; Naoki Miura; Aki Togashi; Takaharu Miyauchi; Sadayuki Murayama (848-853).
The aim of the present study was to consider the safety and efficacy of concurrent use of strontium-89 (Sr-89) with external beam radiotherapy (EBRT) for multiple bone metastases, including lesions that require urgent therapy.A retrospective review was performed of a consecutive series of patients who received Sr-89 for multiple bone metastases. Forty-five patients with multiple bone metastases received Sr-89 injection. Since 17 of the 45 patients had osteolytic bone lesions requiring emergent EBRT, they underwent concurrent use of Sr-89 with EBRT (concurrent group). The remaining 28 patients, none of whom had osteolytic lesions requiring urgent EBRT, were given Sr-89 injection only (singularity group). The injection of Sr-89 was to be given during EBRT, or on the day before the first day of EBRT. The dose of EBRT was 30 Gy in 10 fractions or 40 Gy in 20 fractions. Adverse events were evaluated according to hematological toxicity as measured by the Common Terminology Criteria for Adverse Events (V4.0). To assess efficacy, we checked changes in the pain scale and analgesic drug dosages, and the presence or absence of serious complications from bone metastases.Fifteen of 17 patients (88.2 %) in the concurrent group and 17 of 28 patients (60.7 %) in the singularity group reported bone pain relief. A statistically significant difference was found between the two groups, and severe complications (spinal cord compression and pathological fracture) from bone metastases could be prevented in all patients in the concurrent group. Severe hematological toxicity (grade 3 or higher) was not observed in the two groups. There was no statistical difference between the two groups. No one required additional intervention. The adverse events were tolerable.The results of our study suggest that concurrent use of Sr-89 with EBRT for multiple bone metastases can be performed safely if it is carried out with care, and that it may be an effective therapy in cases requiring emergency treatment.
Keywords: Strontium-89; External beam radiotherapy; Concurrent; Multiple bone metastases

Clinical significance of dual-time-point 18F-FDG PET imaging in resectable non-small cell lung cancer by Katsuhiko Shimizu; Riki Okita; Shinsuke Saisho; Takuro Yukawa; Ai Maeda; Yuji Nojima; Masao Nakata (854-860).
The maximal standardized uptake value (SUVmax) of pulmonary lesions on dual-time-point (DTP) fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for differentiation between malignant and non-malignant pulmonary lesions, and also to be of value for intrathoracic nodal staging of non-small cell lung cancer (NSCLC). However, a few NSCLC lesions have been found to show decreased FDG uptake on delayed images, and the significance of this finding remains unknown.We conducted a retrospective review of the data of 284 patients with NSCLC who underwent DTP FDG-PET before surgery. Cases of adenocarcinoma in situ and minimally invasive adenocarcinoma were excluded, because these lesions show little FDG uptake. Each patient was scanned at 60 min (early acquisition; SUV-E) and 115 min (delayed acquisition; SUV-D) after the radiopharmaceutical injection. The intratumoral retention index (RI) of 18F-FDG was measured for each examination by the DTP method. Recurrence-free survival (RFS) was determined by the Kaplan–Meier method and compared in relation to the SUV-E, SUV-D, and RI by univariate and multivariate analysis using models including the clinico-pathological prognostic factors.Of the 284 cases, the RI ≤ 0 was in 49 cases (17.3 %). This group of patients showed lower values of SUV-E and SUV-D, a smaller tumor size, and a lower rate of lymphatic invasion or vascular invasion. It was particularly noteworthy that lymph node metastasis was not histopathologically confirmed in any of these patients. Univariate analysis identified the RI, SUV-E and SUV-D, besides age, tumor size, lymph node metastasis, and tumor differentiation grade as predictors of the RFS. On the other hand, multivariate analysis identified the RI and lymph node metastasis, but not the SUV-E and SUV-D, as independent predictors of the RFS.This study demonstrated that DTP FDG-PET of the primary tumor in NSCLC can be useful to predict the RFS of the patients. In addition, this method may also be useful to predict the presence/absence of intrathoracic lymph node metastasis in these patients.
Keywords: Non-small cell lung cancer; Lymph node metastasis; Dual-time-point imaging 18F-FDG PET; Retention index

Detection of local recurrence of prostate cancer after radical prostatectomy: Is there a role for early 18F-FCH PET/CT? by Daniele Di Biagio; Agostino Chiaravalloti; Mario Tavolozza; Paolo Abbatiello; Orazio Schillaci (861-869).
To investigate the diagnostic performance of early acquisition compared to late imaging for the detection of local recurrence of prostate cancer by means of 18F-FCH PET/CT.99 patients with radical prostatectomy (mean PSA 3.9 ± 5.03) were subjected to early dynamic PET/CT acquisition of the pelvis and a whole body PET/CT in the same exam session. None of the patients examined was subjected to radiotherapy for local or distant recurrence. All the subjects were taken off hormonal therapy.58 subjects did not show local recurrence in both early and late acquisition, 22 were positive in both modalities, 10 showed a positive early and a negative late acquisition while 9 showed a negative early and a positive late acquisition (Cohen’s k = 0.558). When the results of imaging modalities were considered separately, sensitivity, specificity, positive predictive value and negative predictive value resulted: 78.9, 96.7, 93.8 and 88.1 % for early acquisition and 73.7, 95.1, 90.3 and 85.3 % for late acquisition, respectively. When the results of early and late acquisition were considered together, results were 97.4, 93.4, 90.2 and 98.3 %, respectively.The combination of early acquisition with late acquisition lead to an increase of the diagnostic accuracy of 18F-FCH PET/CT for the diagnosis of local recurrence in prostate cancer.
Keywords: 18F-FCH PET/CT; Local recurrence; Early acquisition; Prostate cancer; PSA

Preparation, quality control and biodistribution assessment of 153Sm-BPAMD as a novel agent for bone pain palliation therapy by Ali Rabie; Razieh Enayati; Hassan Yousefnia; Amir Reza Jalilian; Mojtaba Shamsaei; Samaneh Zolghadri; Ali Bahrami-Samani; Mohammad Hosntalab (870-876).
Various phosphonate ligands labeled with β-emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed. 153Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (153Sm-BPAMD) complex was prepared using BPAMD ligand and 153SmCl3. The effect of various parameters on the labeling yield of 153Sm-BPAMD including ligand concentration, pH, temperature and reaction time were studied. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies (SPECT imaging and scarification) were performed after injection of the complex to Syrian mice up to 48 h post-injection. The biodistribution of the complex was compared with the biodistribution of the 153Sm cation in the same type mice. 153Sm-BPAMD was prepared in high radiochemical purity >98 % and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bound to HA. At the pH 7.4, LogP o/w was −1.86 ± 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue.The results show that 153Sm-BPAMD has interesting characteristics as an agent for bone pain palliation; however, further biological studies in other mammals are still needed.
Keywords: Sm-153; BPAMD; Bone pain palliation

Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT by Steven P. Rowe; Michael A. Gorin; Hans J. Hammers; M. Som Javadi; Hazem Hawasli; Zsolt Szabo; Steve Y. Cho; Martin G. Pomper; Mohamad E. Allaf (877-882).
Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, 18F-fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose.Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer 18F-DCFPyL, an inhibitor of the prostate-specific membrane antigen at 60 min post injection. 18F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease.In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal 18F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. 18F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUVmax) for the identified lesions of 1.6–19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for 18F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9 %).PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as 18F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with agents targeting the neovasculature.
Keywords: Prostate-specific membrane antigen (PSMA); Renal cell carcinoma (RCC); Positron emission tomography (PET); DCFPyL

Comparison of ultrasonography features and malignancy rate of toxic and nontoxic autonomous nodules: a preliminary study by Ahmet Dirikoc; Sefika Burcak Polat; Zuhal Kandemir; Cevdet Aydin; Didem Ozdemir; Fatma Dilek Dellal; Reyhan Ersoy; Bekir Cakir (883-889).
When a scintigraphically autonomous nodule does not produce thyroid hormones enough to suppress serum thyrotrophin, it is generally defined as nontoxic autonomous nodule. In this study, we aimed to compare clinical and ultrasonographical (US) features and cytological and histopathological results of toxic and nontoxic autonomous nodules.Patients who underwent thyroidectomy and were evaluated with technetium-99m-pertechnetate scintigraphy preoperatively in our institution between May 2008 and December 2014 were identified from medical records. Among these, treatment naïve patients with scintigraphically autonomous thyroid nodules were chosen and classified into toxic (hyperthyroid) and nontoxic (euthyroid) groups. The demographic data, preoperative US features of the nodules, fine needle aspiration biopsy and histopathological results were analyzed.There were 170 (89.0 %) patients with toxic and 21 (11.0 %) patients with nontoxic autonomous nodules. A total of 258 scintigraphically autonomous nodules were analyzed among which 227 were clinically functional (toxic) and 31 were clinically euthyroid (nontoxic). Echogenity, texture, marginal irregularity, presence of halo and macrocalcification were similar in toxic and nontoxic autonomous nodules. Toxic autonomous nodules were significantly bigger and had a significantly higher rate of microcalcification compared to nontoxic ones (p = 0.001 and p = 0.025, respectively). There was no significant difference in terms of cytological diagnosis between toxic and nontoxic autonomous nodules (p = 0.052). Atypia of undetermined significance/follicular lesion of undetermined significance cytology was significantly higher in nontoxic group (p = 0.01). 20 (8.8 %) of 227 toxic and 2 (6.5 %) of 31 nontoxic autonomous nodules were malignant (p = 0.59). Considering all nodules regardless of the thyroid function, 8.5 % of autonomous nodules was malignant.US features and malignancy potential of nontoxic autonomous nodules resemble toxic autonomous nodules. Lower diameter suggests that they can represent a preliminary stage of toxic ones and have potential of toxicity when get bigger in size. There is still a considerable risk of malignancy risk in autonomous nodules whether toxic or not.
Keywords: Toxic nodule; Nontoxic autonomous nodule; Thyroid fine needle aspiration; Thyroid malignancy

Validation of prone myocardial perfusion SPECT with a variable-focus collimator versus supine myocardial perfusion SPECT with or without computed tomography-derived attenuation correction by Tomoko Takamura; Yoriko Horiguchi; Masahiko Kanna; Hirooki Matsushita; Yuta Sudo; Shinnosuke Kikuchi; Tomohiro Ueda; Ryo Sasaki; Yukiko Morita (890-896).
The purpose of this study is to evaluate whether prone myocardial perfusion single-photon emission computed tomography (MPS) with thallium-201 acquired through a variable-focus collimator (IQ-SPECT) can correct for soft-tissue attenuation.Thirty-nine patients underwent thallium-201 stress MPS with IQ-SPECT. Delayed images acquired with the patients in the prone position were compared with delayed images obtained with the patients in the supine position with computed tomography-derived attenuation correction (CTAC) (S-CTAC images) or without CTAC (S-NCTAC images). Quantitative tracer uptake (QTU) and semi-quantitative defect scores were determined for the 17 standard myocardial segments. Segments were categorized into anterior–anteroseptal, lateral, inferior, and apex, and areas with defect decision were determined by using the defect scores.Image quality in the prone images was similar to that of S-NCTAC and S-CTAC images. In male patients, QTU in prone images was equivalent to that in S-CTAC images in the anterior–anteroseptal area, but was significantly lower than that in S-CTAC images in the inferior area. In female patients, QTU in prone images was similar to that in S-CTAC images in the anterior–anteroseptal, lateral, and inferior areas. In male and in female patients, QTU in the apex was significantly greater in the prone images than that in the S-CTAC images. In the combined male and female patient group, the defect decision for prone images was similar to that for S-CTAC images in the anterior–anteroseptal, lateral, and inferior areas. Apical defects were observed more frequently in S-CTAC images than in prone or S-NCTAC images.Fewer artificial defects were observed in the apex of images acquired by prone imaging than by S-CTAC imaging. Prone images improved attenuation and had similar defect decision as S-CTAC images in the anterior–anteroseptal, lateral, and inferior areas.
Keywords: IQ-SPECT; Multifocal collimator; Prone imaging; CT-derived attenuation correction; Myocardial perfusion imaging

The maximum standardized uptake value (SUVmax) of FDG-PET/CT is commonly used as an indicator to evaluate the invasiveness and prognosis of non-small-cell lung cancers (NSCLC). We investigated the correlation between SUVmax and tumor invasiveness or postoperative recurrence of solid type NSCLC and compared squamous cell carcinoma (SCC)/adenosquamous carcinoma (ASC) to adenocarcinoma (AC).A retrospective review of preoperative PET/CT, thin-section CT, and postoperative pathological records obtained over a 5-year period was conducted. Solid type NSCLC tumors on thin-section CT with confirmed diagnosis from surgical resection (diameter ≤3 cm) were included. Multivariate logistic regression was used to evaluate the correlation between tumor characteristics and pathological prognostic factors or postoperative recurrence.150 patients (111 males, 39 females; mean age 67 years; 106 cases of AC, 36 cases of SCC, and 8 cases of ASC) were included. SUVmax was significantly correlated with pleural involvement (p = 0.047), lymphatic permeation (p = 0.003), lymph node metastasis (p = 0.027), and tumor invasiveness (p < 0.001). Receiver operating characteristic analysis indicated an optimal SUVmax threshold of 5.0 for tumor invasiveness. Histopathological type was significantly correlated with pleural involvement (p = 0.042), but not with other types of invasiveness. Twenty-nine patients experienced postoperative recurrence. SUVmax was significantly correlated with tumor recurrence (p = 0.004), but size and histopathological type were not (p = 0.502 and p = 0.351, respectively).SUVmax of the primary lesion in solid type NSCLC was significantly correlated with tumor invasiveness and postoperative recurrence. No differences in tumor invasiveness were observed between solid type AC and SCC/ASC. However, in solid type AC, SUVmax of the primary lesion was more significantly correlated with recurrence.
Keywords: Non-small-cell lung cancer; Adenocarcinoma; Squamous cell carcinoma; Adenosquamous carcinoma; Positron emission tomography

The aim of this study is to evaluate the correlation of the serum neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and mean platelet volume (MPV), with the standardized uptake value (SUVmax), and metabolic tumor volume (MTV) in F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patient with esophageal squamous cell cancer at baseline.PET/CTs were performed in 52 patients with esophageal squamous cell cancer, making up the patient group. An additional 52 patients who underwent endoscopy due to dyspepsia with normal esophagus (as a control group) were included in the study to compare the hematological parameters between the patient groups.The median age was 60.0 ± 12.8 years (range 39–84 years) for the patients with esophageal cancer, and 56.9 ± 12.3 years for the control group. Statistical differences were found in terms of the neutrophils, lymphocytes, NLR, PLT, PLR, and MPV between the patients with esophageal cancer and the control group. In the correlation analysis, only the NLR was correlated with the MTV for all of the patients (p = 0.013, r = 0.344). The SUVmax was not correlated with these hematological parameters.At baseline neutrophil-to-lymphocyte ratio is associated with the metabolic tumor volume, which was assessed using the PET/CT in patients with esophageal squamous cell cancer. The SUVmax values were not related to these parameters.
Keywords: F-18 FDG PET-CT; Esophagus squamous cell cancer; SUV; MTV; NLR

Evaluation of bone scan index change over time on automated calculation in bone scintigraphy by Rini Shintawati; Arifudin Achmad; Tetsuya Higuchi; Hirotaka Shimada; Hiromi Hirasawa; Yukiko Arisaka; Ayako Takahashi; Takahito Nakajima; Yoshito Tsushima (911-920).
Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection.We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of 99mTc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis.The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P < 0.001). Analysis of regional BSI (rBSI) and hot spot number changes of selected 15 true lesions also showed similar increase (P < 0.001). In general, the pelvic segment was the most prone to rBSI changes and the chest segment was the most prone to hot spot number changes. Visual assessment showed that BONENAVI diagnosed some typical artifacts as metastases (hot spots).BONENAVI reading of BSIs and hot spot numbers was highly affected by acquisition time. In serial or follow-up examinations (in particular, for monitoring therapeutic efficacy), acquisition time should be fixed for each patient. Cautious interpretation should be made on segments with high physiological uptake. BONENAVI reading was prone to misinterpretation of artifacts. Visual assessment is necessary to rule out this possibility.
Keywords: Bone scintigraphy; Bone scan index; BONENAVI; Computer-assisted diagnostic software

Age-related changes in FDG brain uptake are more accurately assessed when applying an adaptive template to the SPM method of voxel-based quantitative analysis by Axel Van Der Gucht; Antoine Verger; Eric Guedj; Grégoire Malandain; Gabriela Hossu; Yalcin Yagdigul; Véronique Roch; Sylvain Poussier; Louis Maillard; Gilles Karcher; Pierre-Yves Marie (921-928).
The impact of age is crucial and must be taken into account when applying a voxel-based quantitative analysis on brain images from [18F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET). This study aimed to determine whether age-related changes in brain FDG-PET images are more accurately assessed when the conventional statistical parametric mapping (SPM) normalization method is used with an adaptive template, obtained from analysed PET images using a Block-Matching (BM) algorithm to fit with the characteristics of these images.Age-related changes in FDG-PET images were computed with linear models in 84 neurologically healthy subjects (35 women, 19 to 82-year-old), and compared between results provided by the SPM normalization algorithm applied on its dedicated conventional template or on the adaptive BM template. A threshold P value of 0.05 was used together with a family-wise error correction.The age-related changes in FDG-PET images were much more apparent when computed with the adaptive template than with the conventional template as evidenced by: (1) stronger correlation coefficients with age for the overall frontal and temporal uptake values (respective R 2 values of 0.20 and 0.07) and (2) larger extents of involved areas (13 and 5 % of whole brain template volume, respectively), leading to reveal several age-dependent areas (especially in dorsolateral prefrontal, inferior temporal/fusiform and primary somatosensory cortices).Age-related changes in brain FDG uptake may be more accurately determined when applying the SPM method of voxel-based quantitative analysis on a template that best fits the characteristics of the analysed TEP images.
Keywords: 18F-fluorodeoxyglucose; Positron emission tomography; Age; Spatial normalization; Statistical parametric mapping; Block-Matching algorithm