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1.
J Nucl Med ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960713

ABSTRACT

Meta-[123I]iodobenzylguanidine ([123I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [123I]MIBG with the new PET tracer meta-[18F]fluorobenzylguanidine ([18F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [18F]MFBG LAFOV PET/CT and compare it with [123I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [123I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [123I]MIBG scintigraphy and SPECT/low-dose CT, [18F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [123I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [18F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [18F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [123I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [18F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [18F]MFBG LAFOV PET/CT compared with [123I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [18F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma.

2.
Diagnostics (Basel) ; 13(21)2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37958190

ABSTRACT

We performed a systematic evaluation of the diagnostic performance of LAFOV PET/CT with increasing acquisition time. The first 100 oncologic adult patients referred for 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose PET/CT on the Siemens Biograph Vision Quadra were included. A standard imaging protocol of 10 min was used and scans were reconstructed at 30 s, 60 s, 90 s, 180 s, 300 s, and 600 s. Paired comparisons of quantitative image noise, qualitative image quality, lesion detection, and lesion classification were performed. Image noise (n = 50, 34 women) was acceptable according to the current standard of care (coefficient-of-varianceref < 0.15) after 90 s and improved significantly with increasing acquisition time (PB < 0.001). The same was seen in observer rankings (PB < 0.001). Lesion detection (n = 100, 74 women) improved significantly from 30 s to 90 s (PB < 0.001), 90 s to 180 s (PB = 0.001), and 90 s to 300 s (PB = 0.002), while lesion classification improved from 90 s to 180 s (PB < 0.001), 180 s to 300 s (PB = 0.021), and 90 s to 300 s (PB < 0.001). We observed improved image quality, lesion detection, and lesion classification with increasing acquisition time while maintaining a total scan time of less than 5 min, which demonstrates a potential clinical benefit. Based on these results we recommend a standard imaging acquisition protocol for LAFOV PET/CT of minimum 180 s to maximum 300 s after injection of 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose.

4.
Sci Rep ; 12(1): 19126, 2022 11 09.
Article in English | MEDLINE | ID: mdl-36352036

ABSTRACT

Strong prognostic biomarkers are lacking regarding the stratification of treatment and surveillance regimens in head and neck squamous cell carcinoma (HNSCC). The study aimed to assess the prognostic value of soluble urokinase-type plasminogen activator receptor in plasma (suPAR) compared to evaluation by uPAR-positron-emission-tomography (PET) in HNSCC patients. Plasma from 19 controls and 49 HNSCC patients referred to curatively intended radiotherapy (2017-2021) was collected pre-treatment and post-treatment (n = 37). Information on uPAR-PET was available from previous evaluation. Patient median suPAR was significantly higher pre- and post-treatment compared to controls (p = 0.013, p = 0.003) and increased significantly during radiotherapy (p = 0.003). Pre-treatment suPAR did not predict survival outcomes. Post-treatment suPAR significantly predicted RFS (HR = 6.67 (95% CI 1.44-30.9) p = 0.015), but not OS (HR = 3.29 (95% CI 0.882-12.3) p = 0.076) in univariate analysis. RFS prediction was maintained for post-treatment suPAR in multivariate analysis, including TNM-stage (HR = 6.62 (95% CI 1.40-31.4) p = 0.017). Pre-treatment uPAR-PET/CT and post-treatment suPAR was available in 24 patients. High uPAR-estimates on both modalities was significantly associated with poor RFS compared to patients with low uPAR-estimates (log-rank, p = 0.008). Patients with discordant uPAR-estimates (one-low/one-high) were at intermediate risk, although non-significant (p = 0.131). In conclusion, pre-treatment suPAR did not predict RFS or OS. Pre-treatment uPAR-PET and post-treatment suPAR predicted RFS.


Subject(s)
Head and Neck Neoplasms , Receptors, Urokinase Plasminogen Activator , Humans , Positron Emission Tomography Computed Tomography , Squamous Cell Carcinoma of Head and Neck , Tomography, X-Ray Computed , Liquid Biopsy , Head and Neck Neoplasms/diagnostic imaging , Urokinase-Type Plasminogen Activator
5.
Diagnostics (Basel) ; 11(2)2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33671860

ABSTRACT

Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system. With an incidence of 0.17/million individuals and a slight male preference, HS presents with a wide age distribution. Most commonly, it occurs as a primary malignancy. In approximately 25% of the cases a presumed transdifferentiation of a preexisting hematolymphoid disorder can be demonstrated. The clinical presentation varies from a localized solitary mass to severe disseminated disease often with extranodal involvement including skin, soft tissue, the gastrointestinal tract and the hematopoietic system. Systemic symptoms in terms of weight loss, fever and night sweats often occur. The diagnostic work-up of HS is extremely challenging due to the rarity of the disease as well as a wide differential diagnosis in terms of a histologic overlap with diverse mimics. No standardized treatment for HS exists and especially in a disseminated disease the clinical course is overly aggressive with a dismal outcome. The median overall survival from the time of diagnosis is approximately six months. We report a 43-year-old previously healthy Caucasian male admitted to our hospitals with abdominal pain and a feeling of fatigue. We demonstrate both the challenges of a correct diagnosis and an effective treatment as well as the aggressive nature of histiocytic sarcoma.

6.
Diagnostics (Basel) ; 10(9)2020 Sep 18.
Article in English | MEDLINE | ID: mdl-32962163

ABSTRACT

Primary cardiac tumors are extremely rare, with an incidence of 0.001-0.03%. Twenty-five percent of these tumors are malignant, with sarcomas accounting for approximately 95%. Cardiac intimal sarcoma is the least reported subtype of primary cardiac sarcoma. These endocardial mesenchymal tumors most often arise from great arterial vessels, and are rarely located in the heart. They often present with an aggressive clinical course and have a poor prognosis, with surgical resection with achievement of free margins being the mainstay of treatment. This emphasizes the importance of an early, correct diagnosis and timely intervention. We report a 60-year-old Caucasian male with several former cardiac surgical procedures due to congenital aortic stenosis, presenting with functional mitral stenosis/insufficiency and left ventricular outflow tract obstruction (LVOTO) due to massive masses in the left ventricle and atrium of the heart. Hybrid imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) was performed prior to surgery to characterize the intracardiac masses and estimate tumor burden, as well as to identify a potential extracardiac primary malignancy.

8.
Diagnostics (Basel) ; 8(2)2018 Apr 22.
Article in English | MEDLINE | ID: mdl-29690555

ABSTRACT

Polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV) are related rheumatic diseases which are occasionally present concomitantly. PMR is characterized by synovitis and bursitis. In LVV, inflammation of the blood vessel wall is seen. Both disorders can be difficult to diagnose since patients often present non-specific symptoms and results of blood tests. The non-specific symptoms cannot always be distinguished from symptoms indicating an occult malignancy. We present a case of PMR and LVV in a Scandinavian man visualized on [18F]-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) with the presentation of typically affected sites of joints and arteries and with the same imaging modality ruling out occult malignancy.

9.
Clin Nucl Med ; 42(12): e519-e522, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29035997

ABSTRACT

Angiosarcomas are highly malignant and rare tumors of vascular or lymphatic endothelial cell origin with a poor prognosis. Lymphangiosarcoma associated with chronic lymphedema is known as Stewart-Treves syndrome. Stewart-Treves syndrome is primarily described in patients with lymphedema of an upper extremity occurring after breast cancer surgery including radical axillary lymph node dissection and subsequent radiotherapy. It is rarely described in the presence of idiopathic chronic lymphedema of the lower extremities. We present a case of lymphangiosarcoma visualized on F-FDG PET/CT, where Stewart-Treves syndrome is secondary to probably a combination of idiopathic chronic lymphedema of the lower extremities and systemic immunosuppressive treatment.


Subject(s)
Fluorodeoxyglucose F18 , Hemangiosarcoma/complications , Hemangiosarcoma/diagnostic imaging , Lower Extremity/diagnostic imaging , Lymphangiosarcoma/complications , Lymphangiosarcoma/diagnostic imaging , Lymphedema/complications , Positron Emission Tomography Computed Tomography , Chronic Disease , Female , Humans , Lower Extremity/pathology , Middle Aged
10.
J Nucl Med ; 58(7): 1058-1064, 2017 07.
Article in English | MEDLINE | ID: mdl-28082437

ABSTRACT

A fast-track pathway has been established in Denmark to investigate patients with serious nonspecific symptoms and signs of cancer (NSSC), who are not eligible to enter an organ-specific cancer program. The prevalence of cancer in this cohort is approximately 20%. The optimal screening strategy in patients with NSSC remains unknown. The aim of the study was to investigate whether 18F-FDG PET/CT was superior to CT as an initial imaging modality in patients with NSSC. In a randomized prospective trial, the imaging modalities were compared with regard to diagnostic performance. Methods: Two hundred patients were randomized 1:1 to whole-body 18F-FDG PET/CT or CT of the thorax and abdomen as the imaging modality. A tentative diagnosis was established after first-line imaging. The final referral diagnosis was adjudicated by the physician, when sufficient data were available. Results: One hundred ninety-seven patients were available for analysis because 3 patients withdrew consent before scanning. Thirty-nine (20%) patients were diagnosed with cancer, 10 (5%) with an infection, 15 (8%) with an autoimmune disease, and 76 (39%) with other diseases. In the remaining 57 patients (28%), no specific disease was found. 18F-FDG PET/CT had a higher specificity (96% vs. 85%; P = 0.028) and a higher accuracy (94% vs. 82%; P = 0.017) than CT. However, there were no statistically significant differences in sensitivity (83% vs. 70%) or negative predictive values (96% vs. 92%). No difference in days to final referral diagnosis according to randomization group could be shown (7.2 vs. 7.6 d). However, for the subgroups in which the imaging modality showed a suggestion of malignancy, there was a significant delay to final diagnosis in the CT group compared with the 18F-FDG PET/CT group (11.6 vs. 5.7 d; P = 0.02). Conclusion: Compared with CT, we found a higher diagnostic specificity and accuracy of 18F-FDG PET/CT for detecting cancer in patients with NSSC. 18F-FDG PET/CT should therefore be considered as first-line imaging in this group of patients.


Subject(s)
Early Detection of Cancer/statistics & numerical data , Fluorodeoxyglucose F18 , Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/statistics & numerical data , Tomography, X-Ray Computed/methods , Whole Body Imaging/statistics & numerical data , Denmark/epidemiology , Early Detection of Cancer/methods , Female , Humans , Male , Neoplasms/epidemiology , Observer Variation , Positron Emission Tomography Computed Tomography/methods , Prevalence , Radiopharmaceuticals , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Symptom Assessment , Whole Body Imaging/methods
11.
Clin Physiol Funct Imaging ; 37(6): 710-716, 2017 Nov.
Article in English | MEDLINE | ID: mdl-27005324

ABSTRACT

Myocardial perfusion imaging (MPI) holds an important place as non-invasive risk assessment in patients with intermediate risk of coronary heart disease (CHD). However, as much as 60-70% of MPI scans are normal. This study evaluates the role of coronary artery calcium scoring (CAC score) and NT-proBNP as potential gatekeepers for MPI. Patients with intermediate risk of CHD referred for standard MPI were included. CAC score and NT-proBNP were both assessed at the day of the stress study. Sensitivity, specificity and NPV for prediction of abnormal MPI scans were calculated for CAC, NT-proBNP and the combination hereof. A total of 190 patients were included (mean age 61 ± 12 years, 55% female) of whom 24% had known CHD. In all 30% of the scans were abnormal. CAC score achieved the highest AUC regardless of whether patients with known CHD were included or not [AUC 0·75 95% CI (0·66-0·84) and AUC 0·79 (0·68-0·91)]. As a singular variable, CAC score was the most potent predictor with a sensitivity of 85%, specificity of 39% and NPV 88%. The combination of CAC score<10 and NT-proBNP>26 reached a sensitivity of 98% and NPV 94%, where 8% of scans tentatively could be avoided. In patients referred for MPI with intermediate risk for CHD, a combination of CAC score and NT-proBNP could be used to identify a group of patients where MPI could be averted with a high degree of diagnostic safety.


Subject(s)
Computed Tomography Angiography , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Circulation , Coronary Vessels/diagnostic imaging , Myocardial Perfusion Imaging/methods , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Single Photon Emission Computed Tomography Computed Tomography , Vascular Calcification/diagnostic imaging , Aged , Area Under Curve , Biomarkers/blood , Coronary Artery Disease/blood , Coronary Artery Disease/physiopathology , Coronary Vessels/physiopathology , Female , Humans , Male , Middle Aged , Pilot Projects , Predictive Value of Tests , ROC Curve , Referral and Consultation , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors , Unnecessary Procedures , Vascular Calcification/blood , Vascular Calcification/physiopathology
12.
PET Clin ; 11(4): 453-63, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27593249

ABSTRACT

There is emerging evidence suggesting that PET/MR imaging will have a role in many aspects of musculoskeletal imaging. The synergistic potential of hybrid PET/MR imaging in terms of acquiring anatomic, molecular, and functional data simultaneously seems advantageous in the diagnostic workup, treatment planning and monitoring, and follow-up of patients with musculoskeletal malignancies, and may also prove helpful in assessment of musculoskeletal infectious and inflammatory disorders. The application of more sophisticated MR imaging sequences and PET radiotracers other than FDG in the diagnostic workup and follow-up of patients with musculoskeletal disorders should be explored.


Subject(s)
Magnetic Resonance Imaging/methods , Multimodal Imaging/methods , Musculoskeletal Diseases/diagnostic imaging , Positron-Emission Tomography/methods , Humans , Muscle, Skeletal/diagnostic imaging
13.
Medicine (Baltimore) ; 94(51): e2319, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26705220

ABSTRACT

The aim of the study is to assess the prognostic value of different volume-based calculations of tumor metabolic activity in the initial assessment of patients with high-grade bone sarcomas (BS) and soft tissue sarcomas (STS) using F-18 FDG PET/CT.A single-site, retrospective study from 2002 to 2012 including 92 patients with histologically verified high-grade BS (N = 37) or STS (N = 55). All patients underwent a pretreatment F-18 FDG PET/CT scan. Clinical data were registered. Measurements of the accuracy of metabolic tumor volume with a preset threshold of 40% of the maximum standardized uptake value of primary tumor (MTV40%) and total lesion glycolysis (TLG) as prognostic variables and identification of optimal discriminating cut-off values were performed through ROC curve analysis. Patients were grouped according to the cut-off values. All deaths were considered an event in survival analysis. Kaplan-Meier survival estimates and log-rank test were used to compare the degree of equality of survival distributions. Prognostic variables with related hazard ratios (HR) were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%; 12 BS and 29 STS). Average survival for included patients was 6.5 years (95% CI 5.8-7.3 years) and probability of 5-year survival was 52%. There was a high-significant accuracy of TLG and MTV40% as prognostic variables when looking on all patients and during subgroup analysis. AUCs were higher for TLG than for MTV40%. TLG above optimal cut-off value was the only variable which was independently prognostic for survival throughout multivariate regression analysis of all included patients (P = 0.01, HR 4.78 [95% CI 1.45-15.87]) and subgroup analysis (BS: P = 0.04, HR 11.11 [95% CI 1.09-111.11]; STS: P < 0.05, HR 3.37 [95% CI 1.02-11.11]). No significant results were demonstrated for MTV40%.Volume-based F-18 FDG PET/CT imaging markers in terms of pretreatment estimation of TLG provide supplemental prognostic information to histologic grading, with significant independent properties for prediction of overall survival in patients with high-grade BS or STS.


Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/pathology , Sarcoma/diagnosis , Sarcoma/pathology , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/mortality , Child , Female , Fluorodeoxyglucose F18 , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multimodal Imaging , Positron-Emission Tomography , Prognosis , Proportional Hazards Models , Radiopharmaceuticals , Retrospective Studies , Sarcoma/mortality , Soft Tissue Neoplasms/mortality , Tomography, X-Ray Computed , Tumor Burden , Young Adult
14.
Medicine (Baltimore) ; 94(28): e1142, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26181552

ABSTRACT

To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed. Clinical data were registered. Accuracy of maximum standardized uptake value of primary tumor (SUVmax) and tumor-to-background (T/B) uptake ratio as prognostic variables and identification of cut-off values to group patients were determined. Kaplan-Meier survival estimates and log-rank test were used to compare survival distributions. Prognostic variables were assessed using Cox proportional hazards regression analysis. Forty-one of 92 patients died during follow-up (45%). Average survival was 6.5 years (95% CI 5.8-7.3 years) and probability of 5-year survival was 52%. Accuracy of SUVmax and T/B uptake ratio as prognostic variables in all patients and during subgroup analysis of patients with STS was significant. No significant results for AUCs were registered in patients with BS. Surgery was independently prognostic for survival throughout multivariate regression analysis of all patients (P = 0.001, HR 3.84) and subgroup analysis (BS: P = 0.02, HR 11.62; STS: P = 0.005, HR 4.13). SUVmax was significant as prognostic variable in all patients (P = 0.02, HR 3.66) and in patients with STS (P = 0.007, HR 3.75). No significant results were demonstrated for T/B uptake ratio. Estimation of primary tumor metabolic activity with pretherapeutic SUVmax using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.


Subject(s)
Bone Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Sarcoma/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/metabolism , Bone Neoplasms/mortality , Child , Denmark/epidemiology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , ROC Curve , Radionuclide Imaging , Retrospective Studies , Sarcoma/metabolism , Sarcoma/mortality , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/mortality , Young Adult
15.
Diagnostics (Basel) ; 6(1)2015 Dec 22.
Article in English | MEDLINE | ID: mdl-26838798

ABSTRACT

Angiosarcomas are rare and only represent about 2% of all soft tissue sarcomas. They arise from vascular or lymphatic endothelial cells and are most commonly located in the heart, liver, breast, and skin. Cutaneous angiosarcoma of the scalp is highly malignant and with dismal prognosis. Reported five-year survival is <30%. The mainstay of treatment is surgical resection and adjuvant radiation therapy, but failure rates following local therapy are high. Cutaneous angiosarcoma of the scalp has a predilection for pulmonary metastases with a variety of morphologic patterns on imaging. Metastatic disease in terms of pulmonary thin-walled, cystic lesions, may not be hypermetabolic on (18)F-FDG PET and, as such, could be misinterpreted as benign findings. We present a case demonstrating the diagnostic uncertainty and delay in an elderly male with angiosarcoma of the scalp presenting with metastatic lung lesions following failure of local therapy.

16.
Diagnostics (Basel) ; 5(3): 290-3, 2015 Jul 09.
Article in English | MEDLINE | ID: mdl-26854155

ABSTRACT

Parathyroid carcinoma only represents <1% of all cases of primary hyperparathyroidism (PHPT). Even rare, chronic PHPT may lead to excessive osteoclast activity, and the increased resorption leads to destruction of cortical bone and formation of fibrous cysts with deposits of hemosiderin-so-called brown tumors. These benign, osteolytic lesions may demonstrate FDG-avidity on (18)F-FDG PET/CT, and as such are misinterpreted as skeletal metastases. Regression of the lesions may occur following successful treatment. We present a case demonstrating the diagnostic work-up and follow-up of a patient with PHPT due to parathyroid carcinoma and with presence of brown tumors on (18)F-FDG PET/CT, visualizing the possible role of this imaging modality in the evaluation of treatment response in these patients.

17.
Nucl Med Biol ; 41(3): 254-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24440212

ABSTRACT

INTRODUCTION: The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-D-glucose (FDG) and acetate. METHODS: Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco's Modified Eagle's Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0-1.0 mM). Then the cells were incubated with [(18)F]-FDG (1 µCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for (18)F radioactivity were applied. Cell uptake studies with (14)C-1-acetate under the same conditions were performed on PC3 cells. RESULTS: In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/10(6) cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. CONCLUSIONS: Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.


Subject(s)
Fatty Acids, Nonesterified/pharmacology , Glucose/metabolism , Prostatic Neoplasms/pathology , Acetates/metabolism , Biological Transport/drug effects , Carbon Radioisotopes , Cell Line, Tumor , Fluorodeoxyglucose F18/metabolism , Humans , Male
19.
Nucl Med Biol ; 40(4): 524-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23454248

ABSTRACT

INTRODUCTION: The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts. METHODS: Subcutaneous tumors were produced in nude mice by injection of PC3 and CWR22Rv1 PCa cells. The mice were divided into two groups (Acipimox vs. controls). Acipimox (50mg/kg) was administered by oral gavage 1h before injection of tracers. 1h after i.v. co-injection of 8.2MBq (222 ± 6.0 µCi) (18)F-FDG and~0.0037 MBq (0.1 µCi) (14)C-acetate, (18)F-FDG imaging was performed using a small-animal PET scanner. Counting rates in reconstructed images were converted to activity concentrations. Quantification was obtained by region-of-interest analysis using dedicated software. The mice were euthanized, and blood samples and organs were harvested. (18)F radioactivity was measured in a calibrated γ-counter using a dynamic counting window and decay correction. (14)C radioactivity was determined by liquid scintillation counting using external standard quench corrections. Counts were converted into activity, and percentage of the injected dose per gram (%ID/g) tissue was calculated. RESULTS: FDG biodistribution data in mice with PC3 xenografts demonstrated doubled average %ID/g tumor tissue after administration of Acipimox compared to controls (7.21 ± 1.93 vs. 3.59 ± 1.35, P=0.02). Tumor-to-organ ratios were generally higher in mice treated with Acipimox. This was supported by PET imaging data, both semi-quantitatively (mean tumor FDG uptake) and visually (tumor-to-background ratios). In mice with CWR22Rv1 xenografts there was no effect of Acipimox on FDG uptake, either in biodistribution or PET imaging. (14)C-acetate uptake was unaffected in PC3 and CWR22Rv1 xenografts. CONCLUSIONS: In mice with PC3 PCa xenografts, acute administration of Acipimox increases tumor uptake of (18)F-FDG with general improvements in tumor-to-background ratios. Data indicate that administration of Acipimox prior to (18)F-FDG PET scans has potential to improve sensitivity and specificity in patients with castration-resistant advanced PCa.


Subject(s)
Glucose/metabolism , Hypolipidemic Agents/pharmacology , Prostatic Neoplasms/metabolism , Pyrazines/pharmacology , Animals , Cell Line, Tumor , Cell Transformation, Neoplastic , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Male , Mice , Mice, Nude , Positron-Emission Tomography , Prostatic Neoplasms/pathology , Tissue Distribution/drug effects
20.
Oncol Lett ; 4(1): 131-134, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22807975

ABSTRACT

The correct interpretation of metabolic response in cancer cells to therapy requires knowledge of how tumor-free tissue responds to the same treatment. The aim of this study was to evaluate standardized uptake values (SUVs) in tumor-free regions of patients with metastatic colorectal cancer prior to and following therapy, via the use of 18-fluoride fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). On baseline 18F-FDG PET/CT scans (n=51), volumes of interest (VOI) were obtained from tumor-free tissue (aortic arch, liver and spleen) and SUVs normalized to total body mass were registered. The procedure was repeated for a follow-up scan two weeks following a single administration of the third-line treatment with irinotecan plus cetuximab. The mean differences in SUV prior to and following therapy were non-significant (P>0.05) in all the registered tumor-free regions. Correlation coefficients indicated a significant result between the variables (0.74-0.84; P<0.001). This study suggests that the early assessment of metabolic response may be made following the administration of third-line therapy with irinotecan plus cetuximab in patients with metastatic colorectal cancer refractory to second-line treatment with irinotecan.

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