Prostate specific membrane antigen (PSMA) avid nonprostatic benign and malignant disease: a pictorial review.

Prostate specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is revolutionising the management of prostate cancer (PC) in primary staging and assessment of biochemical recurrence (BCR) through its higher diagnostic accuracy compared to both conventional imaging and previously available PET radiopharmaceuticals. PSMA is a transmembrane glycoprotein, highly expressed in prostate cancer, with its extracellular domain the target for PSMA PET radiopharmaceuticals. However, PSMA expression is not prostate specific and resultant PSMA uptake on PET-CT is not restricted to pathologies arising from the prostate gland. The increasing use of PSMA PET-CT has revealed PSMA uptake in a variety of non-prostatic benign and malignant diseases, which adds complexity to PET-CT interpretation and subsequent clinical management. This pictorial review will provide a thorough knowledge and understanding of the comprehensive range of PSMA avid non-prostatic benign and malignant diseases demonstrable on PSMA PET-CT, whilst highlighting the complimentary nature of other imaging modalities.

Palatine tonsil SUVmax on FDG PET-CT as a discriminator between benign and malignant tonsils in patients with and without head and neck squamous cell carcinoma of unknown primary.

AIM: To analyse the maximum standardised uptake value (SUVmax) ratio between tonsils in patients with and without tonsillar carcinoma to determine useful diagnostic thresholds. MATERIALS AND METHODS: Positron-emission tomography (PET)/computed tomography (CT) examinations of patients with suspected head and neck squamous cell carcinoma (SCC) and controls from April 2013 to September 2016 were reviewed retrospectively. Tonsillar SUVmax ratios (ipsilateral/contralateral for malignant tonsils, maximum/minimum for patients without [controls]) were calculated and used to construct a receiver operating characteristic (ROC) curve. RESULTS: Twenty-five patients had tonsillar carcinoma (mean SUVmax ratio of 2, range 0.89-5.4) and 86 patients acted as controls (mean SUVmax ratio of 1.1, range 1-1.5). Using the ROC, the most accurate SUVmax ratio for identifying malignancy was >1.2 (77% sensitivity, 86% specificity). A potentially more clinically useful SUVmax ratio is ≥1.6 with 62% sensitivity and 100% specificity. CONCLUSION: An SUVmax ratio between tonsils of ≥1.6 is highly suspicious for SCC and could be used to direct site of biopsy. Some malignant tonsils had normal FDG uptake; therefore, PET/CT should not be used to exclude tonsillar cancer. Minor asymmetrical uptake is frequently seen in non-malignant tonsils and does not necessarily require further investigation. Due to the single centre nature of this study and the recognised variation in SUV measurements between PET scans, other centres may need to develop their own cut-offs.

PET/CT and PET/MRI in head and neck malignancy.

Combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) has an established role in the staging of difficult cases of head and neck (HN) squamous cell carcinoma (SCC), looking for an unknown primary, assessing response post-chemotherapy at 3-6 months, and differentiating relapse from treatment effects in patients suspected to have tumour recurrence. The PET NECK trial, comparing PET/CT surveillance versus neck dissection in advanced head and neck cancer showed survival was similar among patients who underwent PET/CT-guided surveillance and those who underwent planned neck dissection, but surveillance was more cost-effective. There is growing interest in the use of hypoxia PET tracers, especially in targeting radiotherapy, where the radiotherapy dose can be boosted in regions of hypoxia; the use of 68Ga peptide tracers in neuroendocrine malignancy and also in the growing field of combined PET/magnetic resonance imaging (MRI). PET/MRI has the advantage of increased anatomical detail and radiation dose reduction combined with the molecular and metabolic data from PET, although PET/CT has the advantage in better sensitivity for imaging lung metastases. Thus far, there is good agreement between PET/CT and PET/MRI with high correlation between semi-quantitative measurements in primary, nodal, osseous, and soft-tissue lesions imaging. PET/MRI may indeed provide greater accuracy than the currently available imaging procedures in the staging and later treatment response evaluation in HNSCC.

Texture analysis of (125)I-A5B7 anti-CEA antibody SPECT differentiates metastatic colorectal cancer model phenotypes and anti-vascular therapy response.

BACKGROUND: We aimed to test the ability of texture analysis to differentiate the spatial heterogeneity of (125)I-A5B7 anti-carcinoembryonic antigen antibody distribution by nano-single photon emission computed tomography (SPECT) in well-differentiated (SW1222) and poorly differentiated (LS174T) hepatic metastatic colorectal cancer models before and after combretastatin A1 di-phosphate anti-vascular therapy. METHODS: Nano-SPECT imaging was performed following tail vein injection of 20 MBq (125)I-A5B7 in control CD1 nude mice (LS174T, n=3 and SW1222, n=4), and CA1P-treated mice (LS174T, n=3; SW1222, n=4) with liver metastases. Grey-level co-occurrence matrix textural features (uniformity, homogeneity, entropy and contrast) were calculated in up to three liver metastases in 14 mice from control and treatment groups. RESULTS: Before treatment, the LS174T metastases (n=7) were more heterogeneous than SW1222 metastases (n=12) (uniformity, P=0.028; homogeneity, P=0.01; contrast, P=0.045). Following CA1P, LS174T metastases (n=8) showed less heterogeneity than untreated LS174T controls (uniformity, P=0.021; entropy, P=0.006). Combretastatin A1 di-phosphate-treated SW1222 metastases (n=11) showed no difference in texture features compared with controls (all P>0.05). CONCLUSIONS: Supporting the potential for novel imaging biomarkers, texture analysis of (125)I-A5B7 SPECT shows differences in spatial heterogeneity of antibody distribution between well-differentiated (SW1222) and poorly differentiated (LS174T) liver metastases before treatment. Following anti-vascular treatment, LS174T metastases, but not SW1222 metastases, were less heterogeneous.

Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure-function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [(18)F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed "theranostics". Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research.

Assessment of changes in tumor heterogeneity following neoadjuvant chemotherapy in primary esophageal cancer.

To assess the changes in computed tomography (CT) tumor heterogeneity following neoadjuvant chemotherapy in esophageal cancer. Thirty-one consecutive patients who received neoadjuvant chemotherapy for esophageal cancer were identified. Analysis of primary tumor heterogeneity (texture) was performed on staging and post-chemotherapy CT scans. Image texture parameters (mean grey-level intensity, entropy, uniformity, kurtosis, skewness, standard deviation of histogram) were derived for different levels of image filtration (0-2.5). Proportional changes in each parameter following treatment were obtained. Comparison between pathological tumor response and texture parameters was analyzed using Mann-Whitney U-test. The relationship between CT texture and overall survival) was estimated using the Kaplan-Meier method. Tumor texture became more homogeneous after treatment with a significant decrease in entropy and increase in uniformity (filter 1.0 and 2.5). Pretreatment (filter 1.5, P = 0.006) and posttreatment standard deviation of histogram (filter 1.0, P = 0.009) showed a borderline association with pathological tumor response. A proportional change in skewness <0.39 (filter 1.0) was associated with improved survival (median overall survival 36.1 vs. 11.1 months; P < 0.001). CT tumor heterogeneity decreased following neoadjuvant chemotherapy and has the potential to provide additional information in primary esophageal cancer.

Differences in regional bone metabolism at the spine and hip: a quantitative study using (18)F-fluoride positron emission tomography.

SUMMARY: This study showed that regional bone blood flow and (18)F-fluoride bone plasma clearance measured by positron emission tomography are three times lower at the hip than the lumbar spine. INTRODUCTION: Measurements of effective bone plasma flow (K (1)), bone plasma clearance (K ( i )) and standardised uptake values (SUV) using (18)F-fluoride positron emission tomography ((18)F-PET) provide a useful means of studying regional bone metabolism at different sites in the skeleton. This study compares the regional (18)F-fluoride kinetics and SUV at the hip and lumbar spine (LS). METHODS: Twelve healthy postmenopausal women with no history of metabolic bone disease apart from two with untreated osteoporosis were recruited. Each subject underwent 60-min dynamic (18)F-PET scans at the LS and proximal femur two weeks apart. K (1), K ( i ) and SUV were measured at the LS (mean of L(1)-L(4)), femoral neck (FN), total hip (TH) and femoral shaft (FS). Differences between sites were assessed using the nonparametric Kruskal-Wallis test with a Bonferroni correction for multiple comparisons. RESULTS: Values of K (1), K ( i ) and SUV at the FN, TH and FS were three times lower than at the LS (p = 0.003). Amongst the proximal femur sites, K ( i ) and SUV were lower at the FS compared with the FN and TH, and SUV was lower at the TH compared with the FN (all p < 0.05). The volume of distribution was lower at the TH and FS compared with the LS (p < 0.05). CONCLUSION: The lower values of K (1), K ( i ) and SUV at the hip suggest that lower bone blood flow in the proximal femur is an important factor explaining the principal reason for the differences in bone fluoride kinetics between the LS and hip sites.

Lymphatic vessels in osteoarthritic human knees.

OBJECTIVES: The distribution and function of lymphatic vessels in normal and diseased human knees are understood incompletely. This study aimed to investigate whether lymphatic density is associated with clinical, histological or radiographic parameters in osteoarthritis (OA). METHODS: Sections of synovium from 60 knees from patients with OA were compared with 60 post mortem control knees (from 37 individuals). Lymphatic vessels were identified using immunohistochemistry for podoplanin, and quantified as lymphatic vessel density (LVD) and lymphatic endothelial cell (LEC) fractional area. Effusion status was determined by clinical examination, radiographs were scored for OA changes, and inflammation grading used haematoxylin and eosin stained sections of synovium. RESULTS: Lymphatic vessels were present in synovia from both disease groups, but were not identified in subchondral bone. Synovial lymphatic densities were independent of radiological severity and age. Synovia from patients with OA displayed lower LVD (z=-3.4, P=0.001) and lower LEC fractional areas (z=-4.5, P<0.0005) than non-arthritic controls. In patients with OA, low LVD was associated with clinically detectable effusion (z=-2.2, P=0.027), but not with histological evidence of synovitis. The negative associations between lymphatics and OA/effusion appeared to be independent of other measured confounders. CONCLUSION: Lymphatic vessels are present in lower densities in OA synovia. Abnormalities of synovial fluid drainage may confound the value of effusion as a clinical sign of synovitis in OA.

Functional imaging techniques in hepatocellular carcinoma.

Novel biological therapies, including tyrosine kinase inhibitors such as sorafenib, improve the survival of patients with unresectable hepatocellular carcinoma. However, assessment of therapeutic efficacy remains challenging with conventional imaging techniques such as ultrasonography, CT or MRI that predominantly rely on size change to detect a treatment response. A beneficial tumour effect may go unrecognized in some patients who do not show tumour shrinkage and conversely, some patients may be maintained on treatment that is not active. This paper explores the use of functional imaging methods that are showing promise in the assessment of hepatocellular carcinoma.

Imaging in the investigation and management of Staphylococcus aureus bacteraemia: a role for advanced imaging techniques.

Staphylococcus aureus bacteraemia (SAB) continues to affect ∼25,000 patients in the UK per year with a high crude mortality of 30% at 90 days. Prompt source control improves outcomes in sepsis and SAB and is included in sepsis guidelines. A recent clinical trial of adjunctive antibiotic treatment in SAB found that the majority of recurrences of SAB were associated with a failure of source management. In this condition, the ability to control the source of infection may be limited by the ability to detect a focus of infection. Echocardiogram is now a routinely used tool to detect such unknown foci in the form of unexpected infectious vegetations. We review the literature to explore the utility of advanced imaging techniques, such as [18F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and magnetic resonance imaging (including whole-body MRI), to detect foci which may otherwise be missed. As unknown foci are associated with increased mortality, we propose that increasing the detection of foci could enable improved source control and result in improved outcomes in SAB.

Does magnetic resonance imaging of the spine have a role in the staging of prostate cancer?

AIMS: Magnetic resonance imaging (MRI) is an effective method for evaluating the spine in patients with a high risk of metastatic disease. The aim of this study was to compare MRI spine with radionuclide bone scan in detecting spinal metastases for staging prostate cancer patients. MATERIALS AND METHODS: A cohort of 99 patients with locally advanced prostate cancer at high risk of skeletal metastasis (prostate-specific antigen>10 ng/ml, composite Gleason score>or=8) or equivocal findings on bone scan were included in the retrospective study, and their MRI spine and bone scans were analysed. RESULTS: Ten patients were detected to have definite spinal metastasis by bone scan, whereas 12 patients had definite skeletal metastasis by MRI spine. Compared with the 'gold standard', derived from clinical and radiological follow-up, the sensitivities for radionuclide bone scan and that for MRI spine for detecting skeletal metastasis were 71.4 and 85.7%, respectively (P=0.023), whereas the specificities were 96.5 and 97.7%, respectively (P=0.95). Of the 34 individual metastatic lesions in the spine, 15 were concordantly positive on both scans, whereas five lesions were positive only by bone scan and 11 positive only by MRI. The addition of MRI spine in the staging for prostate cancer resulted in a change of stage and management plan in seven (7%) patients. CONCLUSION: MRI spine has comparable specificity and slightly better sensitivity than bone scan to detect spinal metastasis from prostate cancer.

The effect of a novel Bayesian penalised likelihood PET reconstruction algorithm on the assessment of malignancy risk in solitary pulmonary nodules according to the British Thoracic Society guidelines.

PURPOSE: British Thoracic Society (BTS) guidelines advocate using FDG PET-CT with the Herder model to estimate malignancy risk in solitary pulmonary nodules (SPNs). Qualitative and semi-quantitative assessment of SPN uptake is based upon analysis of Ordered Subset Expected Maximisation (OSEM) PET images. Our aim was to assess the effect of a Bayesian Penalised Likelihood (BPL) PET reconstruction on the assessment of SPN FDG uptake and estimation of malignancy risk (Herder score). METHODS: Subjects with SPNs who underwent FDG PET-CT between 2014-2017, with histological confirmation of malignancy or histological/imaging follow-up confirmation of benignity were included. Two blinded readers independently classified SPN uptake on both OSEM and BPL (BTS score; 1 = none; 2 = ≤ mediastinal blood pool (MBP); 3 = >MBP but ≤ 2x liver; 4 = >2x liver), with resultant calculation of the Herder score (%) for both reconstructions. RESULTS: 97 subjects with 75 (77%) malignant SPNs were included. BPL increased the BTS score in 25 (26%) SPNs; 9 SPNs (7 malignant) increased from BTS score 2 to 3, 16 (13 malignant) from BTS score 3 to 4, with a mean Herder score increase of 18 ±â€¯22%. The mean Herder score for all SPNs with BPL was higher than OSEM (73 ±â€¯29 vs 68 ±â€¯32%, p = 0.001). There was no difference in Herder model diagnostic performance between BPL and OSEM, with similar areas under the curve (0.84 vs 0.83, p = 0.39). CONCLUSION: BPL increases the Herder score in 26% of SPNs compared to OSEM but does not alter the diagnostic performance of the Herder model.

Loco-regional staging of malignant pleural mesothelioma by integrated 18F-FDG PET/MRI.

AIM: To examine the performance of 18F-FDG PET/MRI in the loco-regional staging of malignant pleural mesothelioma (MPM). METHODS: Consecutive subjects with MPM undergoing pre-operative staging with 18F-FDG PET/CT who underwent a same day integrated 18F-FDG PET/MRI were prospectively studied. Clinical TNM staging (AJCC 7th edition) was performed separately and in consensus by two readers on the 18F-FDG PET/MRI studies, and compared with staging by 18F-FDG PET/CT, and with final pathological stage, determined by a combination of intra-operative and histological findings. RESULTS: 10 subjects (9 male, mean age 68 years) with biopsy-proven MPM (9 epithelioid tumours, 1 biphasic) were included. One subject underwent neo-adjuvant chemotherapy between imaging and surgery and was excluded from the clinical versus pathological stage analysis. Pathological staging was concordant with staging by 18F-FDG PET/MRI in 67% (n = 6) of subjects, and with 18F-FDG PET/CT staging in 33% (n = 3). Pathological T stage was concordant with 18F-FDG PET/MRI in 78% (n = 7), and with 18F-FDG PET/CT in 33% (n = 3) of subjects. Pathological N stage was concordant with both 18F-FDG PET/MRI and 18F-FDG PET/CT in 78% (n = 7) of cases. No subject had metastatic disease. There was good inter-observer agreement for overall PET/MRI staging (weighted kappa 0.63) with moderate inter-reader agreement for T staging (weighted kappa 0.59). All 6 subjects with prior talc pleurodesis demonstrated mismatch between elevated FDG uptake and restricted diffusion in areas of visible talc deposition. CONCLUSION: Clinical MPM staging by 18F-FDG PET/MRI is feasible, and potentially provides more accurate loco-regional staging than PET/CT, particularly in T staging.

Quantitative techniques in 18FDG PET scanning in oncology.

The clinical applications of (18)F-fluoro-2-deoxyglucose ((18)FDG) positron emission tomography (PET) in oncology are becoming established. While simple static scanning techniques are used for the majority of routine clinical examinations, increasing use of PET in clinical trials to monitor treatment response with (18)FDG and novel tracers reflecting different pharmacodynamic end points, often necessitates a more complex and quantitative analysis of radiopharmaceutical kinetics. A wide range of PET analysis techniques exist, ranging from simple visual analysis and semiquantitative methods to full dynamic studies with kinetic analysis. These methods are discussed, focusing particularly on the available methodologies that can be utilised in clinical trials.

Relationships of body habitus and SUV indices with signal-to-noise ratio of hepatic (18)F-FDG PET.

OBJECTIVE: Tissue accumulation of (18)F-FDG is quantified as standardised uptake value (SUV), which may be expressed as the voxel maximum (SUVmax) or mean (SUVmean). SUVmax/SUVmean may be a marker of hepatic steatosis, while the coefficient of variation (CV) of SUV may be a marker of hepatic fat distribution heterogeneity (HFDH). Alternatively, they may reflect low signal-to-noise ratio ('noise') in obese persons in whom hepatic steatosis is common. The study aim was to compare the impact of body size on noise versus SUV and CT density (CTD). METHODS: Dynamic PET was performed (30×1min frames) following FDG injection in 60 patients undergoing routine PET/CT. Hepatic FDG clearance was measured using Patlak-Rutland graphical analysis with abdominal aorta as input. Noise was quantified as the standard deviation (SD) of the plot residuals (ignoring the first 2 frames), normalised to the intercept (NRMSD). SUVmax, SUVmean and CTD were measured from 60min whole body PET/CT. CV of SUV and SD of CTD were quantified in 28/60 patients using texture analysis. RESULTS: NRMSD correlated with weight (r=0.49; p<0.0001) and BMI (r=0.48; p=0.0001). SUVmax, SUVmean, SUVmax/SUVmean, CV of SUV, CTD, and SD of CTD all correlated strongly with weight and BMI (p<0.0001). However, they correlated weakly with NRMSD, the strongest being SUVmax (r=0.34; p=0.008) and SD of CTD (r=0.42; n=28; p=0.026). CONCLUSIONS: Noise is increased in overweight/obese persons but has little effect on SUV indices, CTD and their variabilities. SUVmax/SUVmean and CV of SUV are therefore, to some extent, markers of hepatic steatosis and HFDH, respectively.

Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.

AIM: In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA]-octreotide, 22 ± 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. METHODS: Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software. RESULTS: ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA]-octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than In-[DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). CONCLUSIONS: Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with Lu-[DOTA,Tyr]-octreotate.

Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions.

PURPOSE: 99mTechnetium methylene diphosphonate (99mTc MDP) bone scintigraphy is currently the method of choice for the detection of bone metastases, but 18F-fluoro-deoxy-D-glucose positron emission tomography (18FDG PET) offers superior spatial resolution and improved sensitivity. We have compared 18FDG PET with 99mTc MDP bone scintigraphy in patients with skeletal metastases from breast cancer and have analyzed the data in subgroups based on radiographic characteristics of lesions. PATIENTS AND METHODS: Twenty-three women with breast cancer and confirmed bone metastases were studied with both 99mTC MDP bone scintigraphy and 18FDG PET, and the number of lesions detected and the quantitation of uptake (standardized uptake values [SUVs]) of 18FDG in osteolytic and osteoblastic metastases were compared. Survival was compared for both lytic and blastic bone metastases and for patients with high and low accumulation of 18FDG. RESULTS: 18FDG PET detected more lesions than 99mTc MDP scintigraphy (mean, 14.1 and 7.8 lesions, respectively; P < .01). However, 18FDG detected fewer bone metastases compared with 99mTc MDP scintigraphy in a subgroup of patients with osteoblastic disease (P < .05). Higher SUVs were observed for osteolytic than osteoblastic disease (mean, 6.77 and 0.95, respectively; P < .01). Survival was lower in patients with osteolytic disease compared with the remainder (P=.01). A difference in survival was not found for those patients with high SUVs (> 3.6; P=.4). CONCLUSION: 18FDG PET is superior to bone scintigraphy in the detection of osteolytic breast cancer metastases, which led to a poorer prognosis. In contrast, osteoblastic metastases show lower metabolic activity and are frequently undetectable by PET. The biologic explanation for this observation remains to be elucidated.

Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

Differences in skeletal kinetics between vertebral and humeral bone measured by 18F-fluoride positron emission tomography in postmenopausal women.

We have sought to investigate regional differences in skeletal kinetics between lumbar vertebrae and the humerus of postmenopausal women with 18F-fluoride positron emission tomography (PET). Twenty-six women, mean age 62 years, had dynamic PET scans of the lumbar spine and lower humerus after the injection of 180 MBq 18F-fluoride ion. Plasma arterial input functions (IFs) were calculated from a mean IF measured arterially from 10 women and scaled according to late individual venous activity. Vertebral and humeral time activity curves were measured by placing regions of interest (ROI) over lumbar vertebrae and the humeral shaft. Using a three-compartmental model and nonlinear regression analysis the macroconstant Ki, representing plasma clearance of fluoride to bone mineral, and the individual rate constants K1 (related to regional skeletal blood flow) and k2 to k4 describing transport between plasma, an extracellular fluid compartment and a bone mineral compartment, were measured. Mean vertebral Ki (3.47x10(-2) ml x min(-1) x ml(-1)) and K1 (1.08x10(-1) ml x min(-1) x ml(-1)) were found to be significantly greater than humeral Ki (1.64x10(-2) ml min(-1) ml(-1); P<0.0001) and K1 (3.90x10(-2) ml x min(-1) x ml(-1); P<0.0001) but no significant differences were found in k2, k3, and k4. These findings confirm differences in regional skeletal kinetics between lumbar vertebrae and the lower humerus. These observations may help increase our understanding of the regional differences in pathophysiology and response to treatment that have been observed in sites consisting predominantly of either trabecular or cortical bone. 18F-fluoride PET may prove to be a valuable technique in the noninvasive measurement of regional skeletal metabolism.