Evaluation of Diffusion-Weighted Magnetic Resonance Imaging for Follow-up and Treatment Response Assessment of Lymphoma: Results of an 18F-FDG-PET/CT-Controlled Prospective Study in 64 Patients.

PURPOSE: To determine the value of diffusion-weighted MRI (DWI-MRI) for treatment response assessment in 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-avid lymphoma. EXPERIMENTAL DESIGN: Patients with FDG-avid Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at pretherapeutic 18F-FDG-PET/CT, who had also undergone pretherapeutic whole-body DWI-MRI, were included in this prospective study. Depending on the histologic lymphoma subtype, patients received different systemic treatment regimens, and follow-up DWI-MRI and 18F-FDG-PET/CT were performed at one or more time points, depending on the clinical course. For each follow-up DWI-MRI, region-based rates of agreement, and rates of agreement in terms of treatment response (complete remission, partial remission, stable disease, or progressive disease), relative to the corresponding 18F-FDG-PET/CT, were calculated. RESULTS: Sixty-four patients were included: 10 with HL, 22 with aggressive NHL, and 32 with indolent NHL. The overall region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.4%. For the 51 interim examinations (performed after 1-3 therapy cycles), region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.2%, and for the 48 end-of-treatment examinations, agreement was 99.8%. No significant differences, in terms of region-based agreement between DWI-MRI and 18F-FDG-PET/CT, were observed between the three lymphoma groups (HL, aggressive NHL, indolent NHL; P = 0.25), or between interim and end-of-treatment examinations (P = 0.21). With regard to treatment response assessment, DWI-MRI agreed with 18F-FDG-PET/CT in 99 of 102 follow-up examinations (97.1%), with a κ value of 0.94 (P < 0.0001). CONCLUSIONS: In patients with FDG-avid lymphoma, DWI-MRI may be a feasible alternative to 18F-FDG-PET/CT for follow-up and treatment response assessment.

Evaluation of diffusion-weighted MRI for pretherapeutic assessment and staging of lymphoma: results of a prospective study in 140 patients.

PURPOSE: To determine the value of diffusion-weighted MRI (DWI-MRI) for pretherapeutic imaging of fluorodeoxyglucose (FDG)-avid lymphoma and lymphoma with variable FDG avidity. EXPERIMENTAL DESIGN: Treatment-naïve patients with lymphoma who were referred for whole-body staging were included in this prospective study. Group A included patients with FDG-avid lymphoma (e.g., Hodgkin, diffuse large B-cell, and follicular lymphoma), whereas Group B included patients with lymphoma of variable FDG avidity [e.g., extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)]. All patients underwent DWI-MRI and 18F-FDG- positron emission tomography/computed tomography (PET/CT). Region-based sensitivity and agreement with Ann Arbor staging, relative to the reference standard, were calculated for DWI-MRI, and, in Group B, also 18F-FDG-PET/CT and contrast-enhanced (CE-) CT. RESULTS: In Group A (100 patients), DWI-MRI had a region-based sensitivity of 97%, and with regard to staging, agreed with the reference standard in 94 of 100 patients (κ, 0.92). In Group B (40 patients; 38 MALT lymphomas and 2 small lymphocytic lymphomas/chronic lymphocytic leukemias), DWI-MRI, 18F-FDG-PET/CT, and CE-CT had region-based sensitivities of 94.4%, 60.9%, and 70.7%, respectively. With regard to staging in Group B, DWI-MRI, 18F-FDG-PET/CT, and CE-CT agreed with the reference standard in 37 of 40, 26 of 40, and 24 of 40 patients, with κ values of 0.89, 0.52, and 0.43, respectively. CONCLUSIONS: In patients with FDG-avid lymphoma, DWI-MRI seems to be only slightly inferior to 18F-FDG-PET/CT with regard to pretherapeutic regional assessment and staging. In patients with lymphoma subtypes that show a variable FDG avidity (e.g., MALT lymphoma), DWI-MRI seems to be superior to both 18F-FDG-PET/CT and CE-CT.

Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier.

We attempted to assess regional differences in cerebral P-glycoprotein (P-gp) function by performing paired positron emission tomography (PET) scans with the P-gp substrate (R)-[(11)C]verapamil in five healthy subjects before and after i.v. infusion of tariquidar (2 mg/kg). Comparison of tariquidar-induced changes in distribution volumes (DVs) in 42 brain regions of interest (ROIs) failed to detect significant differences among brain ROIs. Statistical parametric mapping analysis of parametric DV images visualized symmetrical bilateral clusters with moderately higher DV increases in response to tariquidar administration in cerebellum, parahippocampal gyrus, olfactory gyrus, and middle temporal lobe and cortex, which might reflect moderately decreased P-gp function and expression.

Gated cardiac 13N-NH3 PET for assessment of left ventricular volumes, mass, and ejection fraction: comparison with electrocardiography-gated 18F-FDG PET.

UNLABELLED: The purpose of this study was to evaluate myocardial electrocardiography (ECG)-gated 13N-ammonia (13N-NH3) PET for the assessment of cardiac end-diastolic volume (EDV), cardiac end-systolic volume (ESV), left ventricular (LV) myocardial mass (LVMM), and LV ejection fraction (LVEF) with gated 18F-FDG PET as a reference method. METHODS: ECG-gated 13N-NH3 and 18F-FDG scans were performed for 27 patients (23 men and 4 women; mean+/-SD age, 55+/-15 y) for the evaluation of myocardial perfusion and viability. For both 13N-NH3 and 18F-FDG studies, a model-based image analysis tool was used to estimate endocardial and epicardial borders of the left ventricle on a set of short-axis images and to calculate values for EDV, ESV, LVEF, and LVMM. RESULTS: The LV volumes determined by 13N-NH3 and 18F-FDG were 108+/-60 mL and 106+/-63 mL for ESV and 175+/-71 mL and 169+/-73 mL for EDV, respectively. The LVEFs determined by 13N-NH3 and 18F-FDG were 42%+/-13% and 41%+/-13%, respectively. The LVMMs determined by 13N-NH3 and 18F-FDG were 179+/-40 g and 183+/-43 g, respectively. All P values were not significant, as determined by paired t tests. A significant correlation was observed between 13N-NH3 imaging and 18F-FDG imaging for the calculation of ESV (r=0.97, SEE=14.1, P<0.0001), EDV (r=0.98, SEE=15.4, P<0.0001), LVEF (r=0.9, SEE=5.6, P<0.0001), and LVMM (r=0.93, SEE=15.5, P<0.0001). CONCLUSION: Model-based analysis of ECG-gated 13N-NH3 PET images is accurate in determining LV volumes, LVMM, and LVEF. Therefore, ECG-gated 13N-NH3 can be used for the simultaneous assessment of myocardial perfusion, LV geometry, and contractile function.

Combined PET and microdialysis for in vivo assessment of intracellular drug pharmacokinetics in humans.

UNLABELLED: Because many drugs possess an intracellular site of action, the knowledge of intracellular concentration-time profiles is desirable. In the present study, PET, which measures total (i.e., intracellular, extracellular, and intravascular) concentrations of radiolabeled drugs in tissue, and microdialysis, which determines unbound drug concentrations in the extracellular space fluid of tissue, were combined to describe the intracellular pharmacokinetics of a model compound--that is, the (18)F-labeled antibiotic (18)F-ciprofloxacin--in vivo in humans. METHODS: Ten healthy male volunteers received a mixture of 687 +/- 50 MBq of (18)F-ciprofloxacin and 200 mg of unlabeled ciprofloxacin as an intravenous bolus infusion over 10 min. The pharmacokinetics of ciprofloxacin in skeletal muscle tissue were assessed by means of combined PET and in vivo microdialysis for 5 h after drug administration. A 3-compartment pharmacokinetic model was fitted to the tissue concentration-time profiles of ciprofloxacin measured by PET to estimate the rate constants of ciprofloxacin uptake and transport. RESULTS: In muscle tissue, mean total and extracellular peak concentration (C(max)) values of ciprofloxacin of 1.8 +/- 0.4 microg/mL and 0.7 +/- 0.2 microg/mL were attained at 95 +/- 34 min and 48 +/- 20 min after drug administration, respectively. The extracellular-to-intracellular exchange appeared to be very fast, with an estimated rate constant k(3) of 1.69 +/- 0.25 min(-1). An intracellular-to-extracellular concentration ratio (C(intra)/C(extra)) of 3.2 +/- 0.8 was reached at 110 min after injection and followed by sustained intracellular retention of the antibiotic for the remainder of the experiment. The predicted extracellular concentration-time profiles from the compartmental modeling were in good agreement with the measured microdialysis data. CONCLUSION: The results obtained in the present study were in accordance with previous in vitro data describing cellular ciprofloxacin uptake and retention. The presently used PET/microdialysis combination might be useful during research and development of new drugs, for which knowledge of intracellular concentrations is of interest.

Assessment of myocardial perfusion by dynamic N-13 ammonia PET imaging: comparison of 2 tracer kinetic models.

BACKGROUND: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH(3)) positron emission tomography (PET) uses tracer kinetic modeling to analyze time-activity curves. We compared 2 commonly used models with 2 compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary flow reserve (CFR). METHODS AND RESULTS: Seventy-seven patients underwent NH(3) PET at rest and during hyperemia. Time-activity curves for blood pool and myocardial segments were obtained from short-axis images of dynamic sequences. Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF values calculated by 2C and 3C models were 0.98 +/- 0.31 mL.min(-1).g(-1) and 1.11 +/- 0.37 mL.min(-1).g(-1), respectively, at rest (P < .0001) and 2.79 +/- 1.18 mL.min(-1).g(-1) and 2.46 +/- 1.02 mL.min(-1).g(-1), respectively, during hyperemia (P < .01), resulting in a CFR of 3.02 +/- 1.31 and 2.39 +/- 1.15 (P < .0001), respectively. Significant correlation was observed between the 2 models for calculation of resting MBF (r = 0.78), hyperemic MBF (r = 0.68), and CFR (r = 0.68). CONCLUSION: Measurements of MBF and CFR by 2C and 3C models are significantly related. However, quantification of MBF and CFR significantly differs between the methods. This difference needs to be considered when normal values are established or when measurements obtained with different methods need to be compared.

[18F]Ciprofloxacin, a new positron emission tomography tracer for noninvasive assessment of the tissue distribution and pharmacokinetics of ciprofloxacin in humans.

The biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [(18)F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET). Special attention was paid to characterizing the distribution of [(18)F]ciprofloxacin to select target tissues. Healthy volunteers (n = 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin. On day 6, subjects received a tracer dose (mean injected amount, 700 +/- 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [(18)F]ciprofloxacin as an intravenous bolus. Thereafter, PET imaging and venous blood sampling were initiated. Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration. The first application of [(18)F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution. Two different tissue compartments of radiotracer distribution could be identified. The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [t(1/2)s], 68, 57, and 106 min, respectively). The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention (t(1/2), >130 min). The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 +/- 1.0 and 9.9 +/- 4.4, respectively). The brain radioactivity concentrations were very low (<1 kBq. g(-1)) and could therefore not be quantified. Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens. In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated.