Paula Lapa

Combined 18F-Fluoride and 18F-FDG PET/CT Scanning for Evaluation of Malignancy: Results of an International Multicenter Trial

18F-FDG PET/CT is used in a variety of cancers, but because of variable rates of glucose metabolism, not all cancers are reliably identified. 18F− PET/CT allows for the acquisition of highly sensitive and specific images of the skeleton. We prospectively evaluated combined 18F−/18F-FDG as a single PET/CT examination for evaluation of cancer patients and compared it with separate 18F− PET/CT and 18F-FDG PET/CT scans. Methods: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating 18F− PET/CT, 18F-FDG PET/CT, and combined 18F−/18F-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. Results: 18F−/18F-FDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of 18F-FDG PET/CT. In 19 participants, skeletal disease was more extensive on 18F− PET/CT and 18F−/18F-FDG PET/CT than on 18F-FDG PET/CT. In another 29 participants, 18F− PET/CT and 18F−/18F-FDG PET/CT showed osseous metastases where 18F-FDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans. Conclusion: This trial demonstrated that combined 18F−/18F-FDG PET/CT shows promising results when compared with separate 18F− PET/CT and 18F-FDG PET/CT for evaluation of cancer patients. This result opens the possibility for improved patient care and reduction in health-care costs, as will be further evaluated in future trials.

A new method for quantification of hepatobiliary scintigraphy using 99mTc—mebrofenin. A comparative study

A method based upon the application of mathematical techniques of deconvolution on the classical compartmental model for the quantitative study of liver function from hepatobiliary scintigraphy using 99mTc-mebrofenin data is proposed. The theory in which the method is based upon is presented and a comparison with a published methodology of obtaining the hepatic extraction after scintigraphic sudies has been performed using the results on 36 rats studies obtained with the two methods. A highly significant correlation between the two techniques was verified. The characteristics of the two methodologies, the proposed one based upon a theoretical approach and the other one on an empirical approximation are discussed. Comments are made on the interest and limitations of the presented technique that may be an useful tool for the evaluation of hepatic insufficiency.

18F-FDG PET/CT in lung cancer. The added value of quantification

OBJECTIVE To test a software application for the quantification of metabolic heterogeneity and to evaluate its superiority in relation to visual interpretation. To investigate if a quantitative analysis adds information to the interpretation of 18F-FDG-PET/CT. MATERIAL AND METHODS The study analyzed 215 patients with a 18F-FDG-PET/CT done for the initial staging of lung cancer between March 2011 and December 2015. The study included 57 (26.5%) women and 158 (73.5%) men, with ages ranging from 34 to 88 years (mean±SD: 67.23±10.04). There were 82 surgical stages (I, II, IIIA), and 133 non-surgical stages (IIIB, IV). The primary tumour was analyzed quantitatively by obtaining the following parameters: SUVmax, metabolic active tumour volume (MATV), total lesion glycolysis (TLG), and the entropy heterogeneity index (ET). Heterogeneity was assessed visually. Death dates and/or the follow-up time were registered, ranging from 0.70 to 67.60 months (mean±SD: 23.20±17.68). RESULTS In multivariate analysis, ET emerged as a better predictor of survival than visual analysis of heterogeneity that was not statistically significant. The C-index determination demonstrated that all quantitative parameters were statistically-significant predictors of survival. Cut-offs were obtained in order to compare survival times. A multivariate analysis was performed. In the total population, the best predictor was the TNM stage, but MATV, ET, and male gender were statistically significant and independent predictors of survival. In stages without surgical indication, the best predictor was the TNM stage, but the MATV and male gender were statistically significant and independent predictors of survival. In the surgical stages, ET was the only statistically significant and independent predictor of survival. CONCLUSIONS Quantification adds prognostic information to the visual analysis of 18F-FDG-PET/CT.

Assessment of skeletal tumour burden on 18F-NaF PET/CT using a new quantitative method.

Purpose The purpose of this study was to test a method of quantifying skeletal tumour burden with 18F-NaF PET/CT. Patients and methods We retrospectively reviewed the charts of 117 patients who underwent 18F-NaF PET/CT for the detection of bone metastases, 68 women and 49 men, 16–82 years old (mean±SD: 62.9±10.7 years). Mean standardized uptake values (SUVmean) were measured in five anatomic sites to evaluate normal skeleton activity. The influence of sex and age was investigated. Skeletal tumour burden was calculated in 69 exams positive for bone metastases using volumetric data and SUVmean values. Intraobserver and interobserver reproducibility was tested. In 10 patients with breast cancer, skeletal tumour burden in pretreatment and post-treatment 18F-NaF PET/CT was compared with tumour marker and clinical evolution. Results The range of normal skeleton SUVmean for the 410 volume of interests analysed was 2.2–5.9 (mean±SD: 4.4±1.5). A threshold of 10 was chosen to exclude 18F-NaF normal skeleton uptake. An inverse relationship was found between normal skeleton SUVmean and age (r=−0.237; P=0.032). Our results show excellent intraobserver and interobserver reproducibility, with intraclass correlation values of 0.995 and 0.997, respectively. The percentage change in the skeletal tumour burden in response to therapy shows a moderate direct correlation with the percentage variation of the tumour marker (r=0.668; P=0.035). Conclusion The methodology that we used to quantify skeletal tumour burden is easy to perform, highly reproducible and allows for the evaluation of bone tumour response to therapy in a subgroup of breast cancer patients. The possibility of skeletal tumour burden quantification is another advantage of 18F-NaF PET/CT over the visual and subjective interpretation of bone scintigraphy.

Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with Other Diagnostic Imaging Modalities

INTRODUCTION The 18F-NaF positron emission tomography/computed tomography is being considered as an excellent imaging modality for bone metastases detection. This ability was compared with other imaging techniques. MATERIAL AND METHODS We retrospectively evaluated 114 patients who underwent 18F-NaF positron emission tomography/ computed tomography. Of these, 49 patients also had bone scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10 18F-FCH positron emission tomography/computed tomography. We identified the technique that detected the largest number of bone metastases. For the detection of skeletal metastases with the 18F-NaF positron emission tomography/computed tomography study, the contribution of the positron emission tomography component was compared with the contribution of the computed tomography component. Cases in which 18F-NaF positron emission tomography/computed tomography and bone scintigraphy required further additional tests for diagnosis clarification were registered. RESULTS The 18F-NaF positron emission tomography/computed tomography was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was superior to 18F-FDG positron emission tomography/computed tomography in 59% of the patients (p < 0.001) and it was superior to 18F-FCH positron emission tomography/computed tomography in 40% of the patients (p < 0.001). None of the compared imaging techniques were superior to 18F-NaF positron emission tomography/computed tomography. The positron emission tomography component was superior to computed tomography in 35% of the cases (p < 0.001). Further investigation was suggested in only 3.5% of patients who underwent 18F-NaF positron emission tomography/computed tomography (45% for bone scintigraphy) (p < 0.001). DISCUSSION As with other authors, our experience also confirms that 18F-NaF positron emission tomography/computed tomography is an excellent imaging modality for the detection of bone metastases, detecting lesions in more patients and more lesions per patient. CONCLUSION The 18F-NaF positron emission tomography/computed tomography showed a superior ability for the detection of bone metastases when compared with bone scintigraphy, 18F-FDG positron emission tomography/computed tomography and 18F-FCH positron emission tomography/computed tomography.

Combined 18F-fluoride and 18F-FDG PET/CT: a response based on actual data from prospective studies.

Dear Sir, We read with interest the Editorial titled “Critical considerations on the combined use of F-FDG and F-fluoride for PET assessment of metastatic bone disease” by Cheng et al., published in the European Journal of Nuclear Medicine and Molecular Imaging on 22 May 2013 [1]. It is our intention to provide a rebuttal to the Editorial’s viewpoints. In the first paragraph, the authors suggest that combined F-fluoride and F-FDG PET/CT has been proposed as a method to improve cancer diagnosis, staging, and therapy monitoring. In our published work, we acknowledged that this approachmight not work for all patients and we suggested that further evaluation of this proposed imaging modality is warranted to identify the most suitable scenarios for routine clinical use [2]. The authors present incorrectly the chronological timeline of our work. Their reference 4 is indeed our pilot study [3]; however, reference 5 is not a pilot study, but a large prospective international study that enrolled 115 participants diagnosed with cancer at four institutions in Denmark, Portugal, South Africa and the US. In addition, another collaboration with an institution in India resulted in another publication reporting the results of combined F-fluoride and F-FDG PET/CT in another 62 cancer patients [4]. Cheng et al. mention the letters to the Editor published in the Journal of Nuclear Medicine in response to the publication of our pilot study [5, 6], yet they omit our response to these letters [7]. It is first argued that F-FDG PET/CT is superior to bone scintigraphy and therefore there is no advantage to adding F-fluoride PET/CT to F-FDG PET/CT. We find it surprising that the authors used citations of work that compared PET/ CTwith planar scintigraphy to support their perspective. Even a comparison of PET/CT and SPECT/CT may not be fair. F-fluoride PET/CT is superior for bone lesion detection when compared to Tc-MDP planar scintigraphy and SPECT [8–10]. Again, our own data are misrepresented as a pilot study, when in reality we reported the results from 52 patients with cancer who were prospectively enrolled [11]. In our published work we quoted publications that indicate that F-FDG PET/ CT provides unique information regarding the glucose metabolism of certain skeletal lesions [12]. However, other published data suggest that F-FDG PET is less sensitive than bone scintigraphy in the detection of osseous metastatic lesions in prostate cancer, but may be useful in the detection of metastatic nodal and soft tissue disease [13–15]. F-fluoride PET/CTalso correlates with PSA levels that are important for monitoring disease progression [15]. We do acknowledge that F-FDG PET/CToutperforms F-fluoride PET/CT in certain malignancies such as lung cancer [16, 17], but only three of the 115 participants in our study were diagnosed with lung cancer. Cheng et al. mention that although the sensitivity of F-fluoride PET is high for osteoblastic lesions, its low specificity is an important concern. As an example, they mention that degenerative change is the most common finding on F-fluoride imaging with intense uptake, but often has only mild to A. Iagaru (*) Division of Nuclear Medicine and Molecular Imaging, Stanford University Medical Center, 300 Pasteur Dr, Stanford, CA 94305, USA e-mail: aiagaru@stanford.edu

The value of quantitative analysis in 18F-NaF PET/CT

AIM To evaluate the ability of SUVmax to differentiate bone metastases from degenerative lesions, blastic from lytic metastases, as well as to determine the correlation between SUVmax with 18F-NaF and with 18F-FDG. MATERIAL AND METHODS A review was performed on 115 18F-NaF PET/CT studies. Of the 64 patients with bone metastases, 49 (39 women, 10 men, 61±12 years (16-81)), in whom the PET/CT supported the diagnosis of bone metastases, were selected for analysis. A record was made of the SUVmax of a maximum of ten metastases in each patient (total 172: 141 blastic, 31 lytic), as well as four degenerative lesions (total 188) with the greatest 18F-NaF uptake intensity. Of the 49 patients analyzed, 43 also had a 18F-FDG PET/CT performed in which a record was made of the SUVmax values for 18F-FDG calculated in the locations corresponding to the bone metastases observed in the 18F-NaF PET/CT: 128 metastases (106 blastic, 22 lytic). RESULTS The mean of the SUVmax values was significantly higher in metastases than in degenerative lesions, 26.8±17.3 vs. 15.3±6.3 (P<0.001) and in blastic than in lytic metastases, 27.9±18.3 vs. 22.1±11.3 (P=0.03). A SUVmax value above 42 always represented metastases, with all values above 49 representing blastic metastases. Using the SUVmax values, it was possible to predict the occurrence of metastases (AUC=0.723; P<0.001; 95% CI=0.671-0.776). The mean of the SUVmax with 18F-NaF was significantly higher in blastic metastases (27.9±18.3 vs. 22.1±11.3, P=0.03), whereas with 18F-FDG it was significantly higher in lytic ones (3.9±3.4 vs. 9.6±3.3; P<0.01). CONCLUSIONS SUVmax can contribute to the differentiation of metastases from degenerative lesions, and blastic from lytic metastases.

PET/CT with 18F-Fluorocholine in Patients with Prostatic Cancer in Biochemical Recurrence

INTRODUCTION In prostate cancer, after therapy with curative intent, biochemical recurrence frequently occurs. The purpose of this study was to evaluate the impact of PET/CT with 18F-fluorocholine in restaging these patients and in their orientation, and to analyze the effect of the risk stratification, the values of PSA and the hormone suppression therapy, in the technique sensitivity. MATERIAL AND METHODS Retrospective analysis of 107 patients with prostate carcinoma in biochemical recurrence who underwent PET/CT with 18F-fluorocholine in our hospital, between December 2009 and May 2014. RESULTS The overall sensitivity was 63.2% and 80.0% when PSA > 2 ng/mL. It was possible to identify distant disease in 28% of the patients. The sensitivity increased from 40.0%, in patients with low and intermediate risk, to 55.2% in high-risk patients. Without hormonal suppression therapy, the sensitivity was 61.8%, while in the group under this therapy, was 67.7%. DISCUSSION PET/CT with 18F-fluorocholine provided important information even in patients with low levels of PSA, however, with significantly increased sensitivity in patients with PSA > 2 ng/mL. Sensitivity was higher in high-risk patients compared with low and intermediate risk patients, however, without a statistically significant difference. The hormone suppression therapy does not appear to influence uptake of 18F-fluorocholine in patients resistant to castration. CONCLUSIONS In this study, PET/CT with 18F-Fluorocholine showed good results in restaging patients with prostate cancer biochemical recurrence, distinguishing between loco regional and systemic disease, information with important consequences in defining the therapeutic strategy.