Organ S values and effective doses for family members exposed to adult patients following I-131 treatment: a Monte Carlo simulation study.

PURPOSE: To calculate organ S values (mGy∕Bq-s) and effective doses per time-integrated activity (mSv∕Bq-s) for pediatric and adult family members exposed to an adult male or female patient treated with I-131 using a series of hybrid computational phantoms coupled with a Monte Carlo radiation transport technique. METHODS: A series of pediatric and adult hybrid computational phantoms were employed in the study. Three different exposure scenarios were considered: (1) standing face-to-face exposures between an adult patient and pediatric or adult family phantoms at five different separation distances; (2) an adult female patient holding her newborn child, and (3) a 1-yr-old child standing on the lap of an adult female patient. For the adult patient model, two different thyroid-related diseases were considered: hyperthyroidism and differentiated thyroid cancer (DTC) with corresponding internal distributions of 131I. A general purpose Monte Carlo code, MCNPX v2.7, was used to perform the Monte Carlo radiation transport. RESULTS: The S values show a strong dependency on age and organ location within the family phantoms at short distances. The S values and effective dose per time-integrated activity from the adult female patient phantom are relatively high at shorter distances and to younger family phantoms. At a distance of 1 m, effective doses per time-integrated activity are lower than those values based on the NRC (Nuclear Regulatory Commission) by a factor of 2 for both adult male and female patient phantoms. The S values to target organs from the hyperthyroid-patient source distribution strongly depend on the height of the exposed family phantom, so that their values rapidly decrease with decreasing height of the family phantom. Active marrow of the 10-yr-old phantom shows the highest S values among family phantoms for the DTC-patient source distribution. In the exposure scenario of mother and baby, S values and effective doses per time-integrated activity to the newborn and 1-yr-old phantoms for a hyperthyroid-patient source are higher than values for a DTC-patient source. CONCLUSIONS: The authors performed realistic assessments of 131I organ S values and effective dose per time-integrated activity from adult patients treated for hyperthyroidism and DTC to family members. In addition, the authors' studies consider Monte Carlo simulated "mother and baby∕child" exposure scenarios for the first time. Based on these results, the authors reconfirm the strong conservatism underlying the point source method recommended by the US NRC. The authors recommend that various factors such as the type of the patient's disease, the age of family members, and the distance∕posture between the patient and family members must be carefully considered to provide realistic dose estimates for patient-to-family exposures.

Evaluation of dynamic [18F]-FDG-PET imaging for the detection of acute post-surgical bone infection.

Diagnosing bone infection in its acute early stage is of utmost clinical importance as the failure to do so results in a therapeutically recalcitrant chronic infection that can only be resolved with extensive surgical intervention, the end result often being a structurally unstable defect requiring reconstructive procedures. [(18)F]-FDG-PET has been extensively investigated for this purpose, but the results have been mixed in that, while highly sensitive, its specificity with respect to distinguishing between acute infection and sterile inflammatory processes, including normal recuperative post-surgical healing, is limited. This study investigated the possibility that alternative means of acquiring and analyzing FDG-PET data could be used to overcome this lack of specificity without an unacceptable loss of sensitivity. This was done in the context of an experimental rabbit model of post-surgical osteomyelitis with the objective of distinguishing between acute infection and sterile post-surgical inflammation. Imaging was done 7 and 14 days after surgery with continuous data acquisition for a 90-minute period after administration of tracer. Results were evaluated based on both single and dual time point data analysis. The results suggest that the diagnostic utility of FDG-PET is likely limited to well-defined clinical circumstances. We conclude that, in the complicated clinical context of acute post-surgical or post-traumatic infection, the diagnostic utility accuracy of FDG-PET is severely limited based on its focus on the increased glucose utilization that is generally characteristic of inflammatory processes.

F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma.

F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untreated patients. All 3 imaging techniques showed correlations with prognostically relevant baseline parameters: the number of focal lesions (FLs), especially when FDG-avid by PET-computed tomography, was positively linked to high levels of beta-2-microglobulin, C-reactive protein, and lactate dehydrogenase; among gene expression profiling parameters, high-risk and proliferation-related parameters were positively and low-bone-disease molecular subtype inversely correlated with FL. The presence of more than 3 FDG-avid FLs, related to fundamental features of myeloma biology and genomics, was the leading independent parameter associated with inferior overall and event-free survival. Complete FDG suppression in FL before first transplantation conferred significantly better outcomes and was only opposed by gene expression profiling-defined high-risk status, which together accounted for approximately 50% of survival variability (R(2) test). Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy.

CT-based attenuation correction in (82)Rb-myocardial perfusion PET-CT: incidence of misalignment and effect on regional tracer distribution.

PURPOSE: Misalignment of low-dose-CT used for attenuation correction (AC) may cause artifacts in cardiac-PET-CT. The aim was to evaluate incidence and severity of misalignment and its quantitative effects on regional myocardial (82)Rb-distribution. METHODS: Rest/dipyridamole (82)Rb-perfusion-PET-CT studies of 92 consecutive patients were analyzed for misalignment. Two different scanning protocols were employed: the first 57 patients had separate CTs for rest and stress PET. The following 35 patients had one CT at rest, used for AC of rest and stress PET. Misalignment was visually scored on a five-point scale (0 = no, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe). In five representative patients with normal perfusion and low probability of disease, 95 polarmaps were created by shifting CT vs PET prior to reconstruction of attenuation-corrected data sets using dedicated software (three dimensions of space; magnitude of shifts, 5, 10, 14 mm). RESULTS: PET/CT -misalignment was detected in 60% of rest and 67% of stress studies. Alignment for rest was better than that for stress (0.7 +/- 0.7 vs 1.0 +/- 0.9, P = 0.03). Comparison of the two protocols revealed no effect on the alignment of the stress study (1.0 +/- 0.9 vs 1.0 +/- 0.9, P = 0.9). Quantitatively, the largest individual effect of any artificial misalignment was a 25% reduction of relative (82)Rb uptake. With a shift of 1 cm, the largest effect in an individual was a 19% decrease. Anterior wall was most frequently influenced by misalignment, but changes of uptake also occurred in all other segments. CONCLUSIONS: Misalignment between CT and PET in cardiac-PET-CT influences regional tracer distribution in multiple segments. Repeated CT imaging after dipyridamole does not improve alignment. These results emphasize the need for strategies to improve coregistration in clinical imaging protocols.

Determinants of the response of left ventricular ejection fraction to vasodilator stress in electrocardiographically gated (82)rubidium myocardial perfusion PET.

PURPOSE: Myocardial perfusion imaging with (82)Rb PET allows for ECG-gated studies to be obtained early after radiotracer injection, capturing ventricular function close to peak pharmacologic action of dipyridamole. This is different from gated SPECT and may potentially provide additional diagnostic information. We sought to identify potential correlates of the PET-derived ejection fraction response to vasodilator stress. METHODS: One hundred ten consecutive patients undergoing (82)Rb PET myocardial perfusion imaging during evaluation for coronary artery disease were included. Using a GE Discovery STRx PET-CT scanner, ECG-gated images (eight bins) were obtained at rest and 4 min after dipyridamole infusion, 90 s after infusion of 1,480-2,220 MBq of (82)Rb. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were determined using a five-point scoring system and 20-segment model. Ejection fraction was calculated using automated QGS software. RESULTS: Significant reversibility (SDS > or = 4) was found in 23 patients (21%). Mean LVEF in all patients was 47 +/- 13% at rest and 53 +/- 13% during dipyridamole. LVEF increased in 89 patients, and decreased in 17 patients during vasodilation. The change in LVEF was inversely correlated with SDS (r = -0.26; p = 0.007). Additionally, it was inversely correlated with resting LVEF (r = -0.20; p = 0.03) and SSS (r = -0.25; p = 0.009). No significant correlations were observed with SRS, heart rate, blood pressure, age, hypertension, hypercholesterolemia, or pretest likelihood of disease. At multivariate regression analysis, SDS was an independent predictor of the change in LVEF. CONCLUSIONS: Gated (82)Rb PET during pharmacologic stress allows for assessment of the functional response to vasodilation. The magnitude of LVEF increase is determined by stress perfusion/reversible perfusion defects. Functional response to hyperemia may thus be incorporated in future evaluations of diagnostic and prognostic algorithms based on (82)Rb PET.

Autonomic regulation of voltage-gated cardiac ion channels.

Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na(V)1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by beta adrenergically stimulated G-proteins. We demonstrate that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.