Alternative Means of Estimating 131I Maximum Permissible Activity to Treat Thyroid Cancer.

To protect bone marrow from overirradiation, the maximum permissible activity (MPA) of 131I to treat thyroid cancer is that which limits the absorbed dose to blood (as a surrogate of marrow) to less than 200 cGy. The conventional approach (method 1) requires repeated γ-camera whole-body measurements along with blood samples. We sought to determine whether reliable MPA values can be obtained by simplified procedures. Methods: Data acquired over multiple time points were examined retrospectively for 65 thyroid cancer patients, referred to determine 131I uptake and MPA for initial treatment after thyroidectomy (n = 39), including 17 patients with compromised renal function and 22 patients with known (n = 16) or suspected (n = 6) metastases. The total absorbed dose to blood (DTotal) was the sum of mean whole-body γ-ray dose component (Dγ) from uncollimated γ-camera measurements and dose due to ß emissions (Dß) from blood samples. Method 2 estimated DTotal from Dß alone, method 3 estimated DTotal from Dγ alone, and method 4 estimated DTotal from a single 48-h γ-camera measurement. MPA was computed as 200 cGy/DTotal for each DTotal estimate. Results: Method 2 had the strongest correlation with conventional method 1 (r = 0.98) and values similar to method 1 (21.0 ± 13.7 cGy/GBq vs. 21.0 ± 14.1 cGy/GBq, P = 0.11), whereas method 3 had a weaker (P = 0.001) correlation (r = 0.94) and method 4 had the weakest (P < 0.0001) correlation (r = 0.69) and lower dose (16.3 ± 14.8 cGy/GBq, P < 0.0001). Consequently, correlation with method 1 MPA was strongest for method 2 MPA (r = 0.99) and weakest for method 4 (r = 0. 75). Method 2 and method 1 values agreed equally well regardless of whether patients had been treated with 131I previously or had abnormal renal function. Conclusion: Because MPA based on blood measurements alone is comparable to MPA obtained with combined body counting and blood sampling, blood measurements alone are sufficient for determining MPA.

Influence of Multigland Parathyroid Disease on 99mTc-Sestamibi SPECT/CT.

PURPOSE: 99mcTc-sestamibi (MIBI) imaging is performed for preoperative parathyroid lesion localization in patients with primary hyperparathyroidism. Decreased sensitivity in multigland disease (MGD) compared with single-gland disease (SGD) is well recognized for planar and SPECT imaging, but few data are available on MIBI SPECT/CT in MGD. METHODS: We retrospectively analyzed 246 patients with primary hyperparathyroidism who underwent preoperative MIBI SPECT/CT. Surgical and pathology reports were used to confirm numbers, weights, and locations of excised glands. Two experienced physicians independently read MIBI SPECT/CTs, grading lesion certainty on a 5-point scale ("definitely normal" to "definitely abnormal"). RESULTS: Three hundred one parathyroid lesions were excised at surgery. Thirty-nine patients (16%) had MGD, and 207 patients (84%) had SGD; 26 patients had 2 lesions, 10 had 3 lesions, and 3 had 4 lesions. Lesion weights were significantly lower in MGD than in SGD (390 ± 604 vs 866 ± 933 mg, P < 0.0001) and decreased with increasing numbers of lesions (P < 0.0001). MIBI SPECT/CT was less sensitive for MGD than SGD (66% vs 98%, P < 0.0001). Sensitivity was lower for 66 MGD lesions matched to 66 SGD lesions (64% vs 98%, P < 0.0001) and decreased with increasing lesion numbers (ρ = -0.45, P < 0.0001), despite similar weights (526 ± 678 vs 525 ± 686 mg, P = 0.99) and similar locations (P = 0.47). Specificity was similar for MGD (95%) and SGD (90%). CONCLUSIONS: 99mcTc-MIBI SPECT/CT sensitivity is significantly lower in MGD than in SGD. This does not appear to be related to lesion weight or location.

Effect of reconstruction algorithms on the accuracy of (99m)Tc sestamibi SPECT/CT parathyroid imaging.

The superiority of SPECT/CT over SPECT for (99m)Tc-sestamibi parathyroid imaging often is assumed to be due to improved lesion localization provided by the anatomic component (computed tomography) of the examination. It also is possible that this superiority may be related to the algorithms used for SPECT data reconstruction. The objective of this investigation was to determine the effect of SPECT reconstruction algorithms on the accuracy of MIBI SPECT/CT parathyroid imaging. We retrospectively analyzed preoperative MIBI SPECT/CT parathyroid imaging studies performed on 106 patients. SPECT data were reconstructed by filtered back projection (FBP) and by iterative reconstruction with corrections for collimator resolution recovery and attenuation (IRC). Two experienced readers independently graded lesion detection certainty on a 5-point scale without knowledge of each other's readings, reconstruction methods, other test results or final diagnoses. All patients had surgical confirmation of the final diagnosis, including disease limited to the neck, and location and weight of excised lesion(s). There were 135 parathyroid lesions among the 106 patients. For FBP SPECT/CT and IRC SPECT/CT sensitivity was 76% and 90% (p = 0.003), specificity was 87% and 87% (p = 0.90), and accuracy was 83% and 88% (p = 0.04), respectively. Inter-rater agreement was significantly higher for IRC than for FBP (kappa = 0.76, "good agreement", versus kappa = 0.58, "moderate agreement", p < 0.0001). We conclude that the improved accuracy of MIBI SPECT/CT compared to MIBI SPECT for preoperative parathyroid lesion localization is due in part to the use of IRC for SPECT data reconstruction.

Comparison of criteria to truncate gastric emptying tests.

PURPOSE: Standardized scintigraphic gastric emptying (GE) protocols to detect gastroparesis (GP) require collecting data for 4 h. This investigation was undertaken to compare seven methods to reduce the duration of the test. MATERIALS AND METHODS: This was a retrospective study of GE data collected using a standardized protocol at 0, 1, 2, 3, and 4 h for 602 patients being evaluated for GP. The reference standard was GP defined conventionally as percentage of gastric retention (GR) at 4 h (p4) of greater than 10%. For data up to 2 h the results were derived as follows: (a) confirming as being positive for GP if GR at 2 h was greater than 65%, negative for GP if GR at 2 h was less than 45%, and indeterminate otherwise; (b) by linear extrapolation; and (c) by monoexponential extrapolation. For data beyond 2 h, further evaluations were made and results were derived as follows: (a) confirming as being positive for GP if GR at 2.5 h was greater than 40%; (b) ascertainment of GR at 3 h; (c) by biphasic fit; and (d) by observation of maximum GR for normal patients at time points earlier than 4 h. RESULTS: Thirty percent of all patients had GP. Eighty percent were determinate by Method 1; for these patients sensitivity to detect GP was similar (P=0.11) for Methods 1-3 (69-79%). For data beyond 2 h, sensitivity of the seven methods ranged from 64 to 92%, and the sensitivity of every method was significantly lower than that of the reference standard (P<0.001). CONCLUSION: Considering that sensitivity to detect GP was significantly reduced for data collection limited to 3 h or less, it is not advisable to truncate GE studies earlier than 4 h.

Sestamibi parathyroid scintigraphy in multigland disease.

PURPOSE: For sestamibi (MIBI) studies in patients with primary hyperparathyroidism, some investigations found that the test sensitivity is lower in patients with multigland disease (MGD) than in those with single-gland disease (SGD), whereas other investigations reported that the sensitivity of MIBI imaging is similar in MGD and SGD. The objectives of this investigation, therefore, were to determine (a) whether there are differences in the sensitivity and specificity of MIBI imaging for detecting parathyroid lesions in patients with MGD and in patients with SGD, (b) whether there is a relationship between test sensitivity and the number of glands involved, (c) whether there are differences in weight between parathyroid lesions in MGD and SGD, (d) whether there are differences in lesion locations between MGD and SGD, and (e) whether MIBI sensitivity in MGD is related to the number, weight, or location of the lesions. MATERIALS AND METHODS: This was a retrospective investigation of data for 651 patients with biochemically confirmed primary hyperparathyroidism limited to the neck, who underwent preoperative parathyroid lesion localization using a dual tracer 99mTc-MIBI/TcO4⁻ protocol that included early and late planar pinhole 99mTc-MIBI, pinhole thyroid imaging, image subtraction, and single photon emission computed tomography. All patients underwent surgery subsequently. Lesion locations were obtained from operative reports; lesion weights were obtained from pathology reports. One experienced nuclear physician, who had no knowledge of the other test results or the final diagnoses, graded studies on a 5-point scale (0=definitely normal to 4=definitely abnormal) while reading all scintigraphic images simultaneously. RESULTS: There were 851 lesions among the 651 patients. One hundred and thirty-one (20%) patients had MGD and 520 (80%) patients had SGD. Among the patients with MGD, 74 had two lesions, 45 had three lesions, and 12 had four lesions. MIBI imaging was significantly less sensitive (61 vs. 97%, P<0.0001) and specific (84 vs. 93%, P<0.0001) for MGD than for SGD. Weights of MGD lesions were significantly lower than those of SGD lesions [median 190 mg (10-14 600 mg) vs. median 500 mg (48-27 000 mg), Wilcoxon P<0.0001]. Lesion weights decreased significantly with increasing lesion number (r=-0.42, P<0.0001). MIBI sensitivity for 249 MGD lesions (65%) was significantly less (P<0.0001) than for 249 weight-matched SGD lesions (94%). For these weight-matched lesions, the test sensitivity decreased progressively with increasing lesion number (r=0.97, P=0.006). The spatial distribution of MGD and SGD lesions was similar (P=0.19), and the sensitivity was not related to lesion location for MGD (P=0.32) or SGD (P=0.11) lesions. CONCLUSION: MIBI is significantly less sensitive and specific for detecting parathyroid lesions in MGD than in SGD. Decreased sensitivity is not explained by lesion weight or location, and further studies of factors affecting MIBI imaging in MGD are warranted.

Adenosine triphosphate-binding cassette subfamily C member 2 is the major transporter of the hepatobiliary imaging agent (99m)Tc-mebrofenin.

UNLABELLED: The organic anion (99m)Tc-N-[2-[(3-bromo-2,4,6-trimethylphenyl)-amino]-2-oxoethyl]-N-(carboxymethyl)-glycine ((99m)Tc-mebrofenin) and its analogs are widely used for hepatobiliary imaging. Identification of the mechanisms directing bile canalicular transport of these agents will provide insights into the basis of their hepatic handling for assessing perturbations. METHODS: We performed studies in animals, including healthy Fischer 344 rats or rats treated with carbon tetrachloride or intrasplenic cell transplantation and healthy Wistar rats or HsdAMC:TR-Abcc2 mutant rats in Wistar background. Onset of hepatic inflammation was verified by analysis of carbon uptake in Kupffer cells. Hepatic clearance of (99m)Tc-mebrofenin was studied with dynamic imaging, and fractional retention of peak hepatic mebrofenin activity after 60 min was determined. Changes in the expression of bile canalicular transporters were analyzed by real-time polymerase chain reaction and Western blots. RESULTS: Carbon tetrachloride and cell transplantation produced hepatic inflammation with activation of Kupffer cells, resulting in a rapid decline in the expression of the bile canalicular transporters Abcb4, Abcb11, and Abcc2. Among these transporters, decreased expression of Abcc2 was most prominent, and this decline persisted for 4 wk. Next, we examined (99m)Tc-mebrofenin excretion in HsdAMC:TR-Abcc2 mutant rats (in which Abcc2 expression is naturally inactivated), compared with their healthy counterparts. In healthy HsdRccHan:WIST rats, only 23% +/- 3% of the peak (99m)Tc-mebrofenin activity was retained after 60 min. By contrast, in HsdAMC:TR-Abcc2 mutant rats, 73% +/- 5% of the peak (99m)Tc-mebrofenin activity was retained (P < 0.001). Moreover, the administration of cyclosporin A markedly inhibited (99m)Tc-mebrofenin excretion in healthy rats, with no further effect on already impaired (99m)Tc-mebrofenin excretion in HsdAMC:TR-Abcc2 mutant rats. Hepatic excretion of (99m)Tc-mebrofenin was largely dependent on Abcc2. This molecular basis of (99m)Tc-mebrofenin excretion will advance studies of pathophysiologic mechanisms in hepatic Abcc2 pathways.

Molecular pathway-specific 99mTc-N-(3-bromo-2,4,6-trimethyacetanilide) iminodiacetic acid liver imaging to assess innate immune responses induced by cell transplantation.

OBJECTIVES: Inflammatory responses after cell transplantation impair engraftment of transplanted cells. We studied whether perturbations in specific molecular pathways after inflammation in a syngeneic cell transplantation model could be identified by noninvasive imaging. METHODS: After transplanting hepatocytes into the liver of dipeptidyl peptidase IV-deficient Fischer 344 rats, we imaged hepatobiliary excretion of ppmTc-N-(3-bromo-2,4,6-trimethyacetanilide) iminodiacetic acid (99mTc-mebrofenin). Fractional retention of peak hepatic mebrofenin activity over 60-min periods was correlated with parameters of hepatic inflammation. RESULTS: In healthy animals, 28+/-6% 99mTc-mebrofenin activity was in the liver after 60 min, whereas cell transplantation dose-dependently inhibited excretion of 99mTc-mebrofenin, P value of less than 0.001. Resolution of this abnormality in 99mTc-mebrofenin transport required 2 weeks in the setting of prolonged activation of Kupffer cells with increased TNF-alpha and IL-6 expression. Hepatic transport of 00mTc-mebrofenin was promptly restored by anti-inflammatory treatments, including inhibition of cyclooxygenase activity, depletion of neutrophils, or blocking of inflammatory cytokines before cell transplantation. Moreover, these treatments improved transplanted cell engraftment. CONCLUSION: Molecular pathway-based imaging offers appropriate noninvasive means to address activation of innate immune responses. This will help in developing suitable strategies for characterizing and overcoming immune responses for cell and gene therapy.

Pinhole versus parallel-hole collimators for parathyroid imaging: an intraindividual comparison.

UNLABELLED: This study was undertaken to determine the effects of collimators on the accuracy of preoperative sestamibi parathyroid imaging of the neck. METHODS: Forty-nine patients with primary hyperparathyroidism underwent preoperative (99m)Tc-sestamibi parathyroid imaging. The protocol included early and late pinhole and parallel-hole imaging. One experienced nuclear physician, without knowledge of other test results or final diagnoses, interpreted studies. For both pinhole and parallel-hole images, focally increased sestamibi accumulation outside the normal tracer biodistribution that persisted or increased in intensity from early to late images was interpreted as positive for a parathyroid lesion. Final diagnoses were operatively confirmed in all patients. RESULTS: Fifty-four parathyroid lesions were resected from the 49 patients. Forty-five patients had single-gland disease. Four patients had multigland disease: 3 had 2 lesions and 1 had 3 lesions. Median lesion weight was 840 mg. Pinhole imaging was significantly more sensitive than parallel-hole imaging (89% vs. 56%; P = 0.0003) for all 54 lesions. Specificity did not significantly differ between pinhole and parallel-hole imaging (93% vs. 96%, P = 0.29). Pinhole imaging was significantly more sensitive than parallel-hole imaging for lesions above (100% vs. 68%, P = 0.003) and below (77% vs. 42%, P = 0.03) the median weight and for single-gland disease (96% vs. 67%, P = 0.001). Pinhole imaging also was more sensitive for multigland disease, although the difference was only marginally significant (55% vs. 0%, P = 0.037). CONCLUSION: Because sensitivity is significantly higher, sestamibi parathyroid imaging of the neck should be performed with a pinhole collimator.

Preoperative parathyroid scintigraphic lesion localization: accuracy of various types of readings.

PURPOSE: To retrospectively compare the accuracy of various parathyroid scintigraphy readings for single-gland disease (SGD) and multigland disease (MGD) in patients with primary hyperparathyroidism, with histologic analysis as the reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study. Records of 462 patients with primary hyperparathyroidism who underwent preoperative imaging with a technetium 99m ((99m)Tc) sestamibi and (99m)TcO4- protocol that consisted of early and late pinhole (99m)Tc sestamibi, pinhole thyroid imaging, image subtraction, and single photon emission computed tomography (SPECT) were retrospectively reviewed. An experienced nuclear medicine physician without knowledge of other test results or of the final diagnoses graded images on a scale from 0 (definitely normal) to 4 (definitely abnormal). Early pinhole (99m)Tc sestamibi images, late pinhole (99m)Tc sestamibi images, subtraction images, SPECT images, early and late pinhole (99m)Tc sestamibi images, all planar images, and all images--including SPECT images--were read in seven sessions. Receiver operating characteristic curves were generated for each session and were used to calculate sensitivity, specificity, and accuracy. RESULTS: A total of 534 parathyroid lesions were excised. Of the 462 patients, 409 had one lesion, whereas 53 had multiple lesions. Reading all images together was more accurate (89%, P = .001) than was reading early (79%), late (85%), subtraction (86%), and SPECT (83%) images separately; however, it was not significantly more accurate than reading planar images (88%) or early and late images together (87%). Reading all images was significantly less sensitive in the detection of lesions with a median weight of 600 mg or less than in the detection of lesions with a median weight of more than 600 mg (86% vs 94%, P = .004). Per-lesion sensitivity for reading all images was significantly higher for SGD than for MGD (90% vs 66%, P < .001). Sensitivity of reading all images together in the identification of patients with MGD was 62%. CONCLUSION: Reviewing early, late, and subtraction pinhole images together with SPECT images maximizes parathyroid lesion detection accuracy. Test sensitivity is adversely affected by decreasing lesion weight and MGD.

Systemic and local release of inflammatory cytokines regulates hepatobiliary excretion of 99mTc-mebrofenin.

OBJECTIVES: Imaging agents capable of providing cell compartment-specific information will facilitate studies of pathophysiological mechanisms, natural history of diseases, and therapeutic development. To demonstrate the effects of liver injury on the disposal of the organic anion mebrofenin, we performed animal studies. METHODS: Acute liver injury was induced in Fischer 344 rats with 0.25-1 ml/kg single doses of carbon tetrachloride followed by studies of animals over 4 weeks. The liver injury was analyzed by blood tests and histological grading. Additional rats were treated with lipopolysaccharide, interleukin-6 or tumor necrosis factor-alpha to activate inflammatory events. Hepatic clearance of Tc-mebrofenin was studied with dynamic imaging and fractional retention after 60 min of peak hepatic mebrofenin activity was determined. RESULTS: In healthy rats, only 24+/-2% of peak mebrofenin activity was retained in the liver after 60 min. By contrast, 24 h after carbon tetrachloride, virtually all mebrofenin activity was retained in the liver (P<0.001). Three weeks were required for mebrofenin excretion to become normal after carbon tetrachloride administration. In this situation, we found that Kupffer cell activity was increased. In addition, the abnormality in mebrofenin excretion was reproduced by lipopolysaccharide, which activates Kupffer cells. Moreover, mebrofenin excretion was highly sensitive to interleukin-6 and/or tumor necrosis factor-alpha, which help mediate the Kupffer cell response. CONCLUSION: Hepatobiliary excretion of mebrofenin was affected rapidly and over an extended period by inflammatory cytokines released after liver injury. The remarkable sensitivity of mebrofenin excretion to cytokines suggests that Tc-mebrofenin imaging will be helpful for assessing cytokine-mediated liver inflammation.

Diagnosing prosthetic vascular graft infection with the antigranulocyte antibody 99mTc-fanolesomab.

AIM: The objectives of this retrospective investigation were to determine the accuracy of 99mTc-fanolesomab, an antigranulocyte antibody, for diagnosing prosthetic vascular graft infection, ascertain optimum imaging times for this indication, and assess safety of this agent. METHODS: Eighteen patients with 19 prosthetic vascular grafts were included. Indications for graft placement included peripheral vascular disease (8), haemodialysis (7), and aneurysm (4). Patients were imaged 2-5 h and 18-30 h after injection of 555-740 MBq (75-125 microg) 99mTc-fanolesomab. One experienced nuclear physician reviewed images in three separate sessions, early alone, late alone and early plus late images together. When early and late images were read alone, graft activity more intense than native blood pool activity was classified as positive for infection. When early and late images were interpreted together, graft activity which persisted or which increased in intensity over time was classified as positive for infection. Patient records were reviewed for adverse events up to 30 days after injection. RESULTS: Five (26%) prosthetic grafts were infected. Early, late and early plus late imaging were equally sensitive (1.00). Early images were significantly less specific (0.50), than late and early plus late images (0.93) (P<0.05, analysis of proportions). Accuracy of late imaging and early plus late imaging were the same: 0.93. No patient experienced adverse events following radiopharmaceutical injection. CONCLUSIONS: 99mTc-fanolesomab imaging, performed 18-30 h after injection, diagnosed prosthetic vascular graft infection safely and accurately (95%). (Although safety was not an issue in this investigation, following reports of serious, including two fatal, events after administration, 99mTc-fanolesomab was withdrawn from the United States market).

Phantom experiments to improve parathyroid lesion detection.

This investigation tested the hypothesis that visual analysis of iteratively reconstructed tomograms by ordered subset expectation maximization (OSEM) provides the highest accuracy for localizing parathyroid lesions using 99mTc-sestamibi SPECT data. From an Institutional Review Board approved retrospective review of 531 patients evaluated for parathyroid localization, image characteristics were determined for 85 99mTc-sestamibi SPECT studies originally read as equivocal (EQ). Seventy-two plexiglas phantoms using cylindrical simulated lesions were acquired for a clinically realistic range of counts (mean simulated lesion counts of 75 +/- 50 counts/pixel) and target-to-background (T:B) ratios (range = 2.0 to 8.0) to determine an optimal filter for OSEM. Two experienced nuclear physicians graded simulated lesions, blinded to whether chambers contained radioactivity or plain water, and two observers used the same scale to read all phantom and clinical SPECT studies, blinded to pathology findings and clinical information. For phantom data and all clinical data, T : B analyses were not statistically different for OSEM versus FB, but visual readings were significantly more accurate than T : B (88 +/- 6% versus 68 +/- 6%, p = 0.001) for OSEM processing, and OSEM was significantly more accurate than FB for visual readings (88 +/- 6% versus 58 +/- 6%, p < 0.0001). These data suggest that visual analysis of iteratively reconstructed MIBI tomograms should be incorporated into imaging protocols performed to localize parathyroid lesions.

Combined labeled leukocyte and technetium 99m sulfur colloid bone marrow imaging for diagnosing musculoskeletal infection.

The use of labeled leukocyte (white blood cell [WBC]) studies in the diagnosis of osteomyelitis can be problematic. A combined study consisting of WBC imaging and complementary bone marrow imaging performed with technetium 99m (99mTc) sulfur colloid is approximately 90% accurate and is especially useful for diagnosing osteomyelitis in situations involving altered marrow distribution. There are limitations and pitfalls associated with a combined study. If there is no labeled WBC activity in the region of interest, marrow imaging is not useful. The sulfur colloid image becomes photopenic within about 1 week after the onset of infection, so that the study should be interpreted cautiously in the acute setting. Labeled WBC accumulation in lymph nodes can also confound image interpretation, although nodal activity can usually be recognized because it is typically round, discrete, multifocal, linear in distribution, and often bilateral. Furthermore, 99mTc-sulfur colloid that is improperly prepared or is more than about 2 hours old degrades image quality, potentially causing erroneous conclusions. Nevertheless, WBC-marrow imaging is a very accurate technique for diagnosing osteomyelitis. Knowledge of the criteria for image interpretation and of the aforementioned limitations and pitfalls, combined with careful attention to imaging technique, will maximize the value of this study.

PET with FDG-labeled leukocytes versus scintigraphy with 111In-oxine-labeled leukocytes for detection of infection.

PURPOSE: To compare prospectively the accuracy of positron emission tomography (PET) with leukocytes labeled in vitro with (18)F fluorodeoxyglucose (FDG) versus that of conventional scintigraphy with leukocytes labeled in vitro with (111)In oxine in patients suspected of having infection. MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval; informed consent was obtained from all patients. Patients were 25 men and 26 women aged 32-86 years. In vitro labeling of autologous human leukocytes with FDG and (111)In-oxine was performed according to published methods. Labeling efficiencies and cell viability were determined. Imaging was performed 2.5-5.8 hours after injection of 196-315 MBq of FDG-labeled leukocytes and approximately 24 hours after injection of 17-25 MBq of (111)In-oxine-labeled leukocytes. Forty-three (20 men, 23 women; mean age, 59 years; range, 32-86 years) patients could be successfully imaged with both tracers. Six patients were not injected with FDG-labeled leukocytes because of low labeling efficiency (<35%). Two patients were injected with FDG-labeled leukocytes but were not imaged. One reader interpreted all results as positive or negative for infection. Imaging results were compared with final diagnoses. Labeling efficiencies and cell viabilities were compared by using the paired t test. Differences between PET and scintigraphy were determined by using the McNemar test. RESULTS: For the 43 patients who were imaged with both tracers, labeling efficiency of FDG was lower than that of (111)In oxine (72% +/- 8 [standard deviation] vs 90% +/- 5, P < .001). Viability of FDG-labeled leukocytes was not different from that of (111)In-oxine-labeled leukocytes (98% +/- 1 vs 97% +/- 3). There were no differences between FDG PET and (111)In scintigraphy in terms of sensitivity (87% vs 73%), specificity (82% vs 86%), or accuracy (84% vs 81%). CONCLUSION: PET with FDG-labeled leukocytes was comparable to scintigraphy with (111)In-oxine-labeled leukocytes. Further investigation in a larger population with dedicated PET or PET/computed tomography seems warranted.

Radionuclide imaging of the parathyroid glands.

The parathyroid glands, which usually are situated behind the thyroid gland, secrete parathyroid hormone, or PTH, which helps maintain calcium homeostasis. Primary hyperparathyroidism results from excess parathyroid hormone secretion. In secondary hyperparathyroidism, the normal PTH effect on bone calcium release is lost. Serum PTH rises, causing generalized hyperplasia. In tertiary hyperparathyroidism, a complication of secondary hyperparathyroidism, normal feedback mechanisms governing PTH secretion are lost, parathyroid gland sensitivity to PTH decreases, and the threshold for inhibiting PTH secretion increases. 99mTc sestamibi, or MIBI, the current radionuclide study of choice for preoperative parathyroid localization, can be performed in various ways. The "single-isotope, double-phase technique" is based on the fact that MIBI washes out more rapidly from the thyroid than from abnormal parathyroid tissue. However, not all parathyroid lesions retain MIBI and not all thyroid tissue washes out quickly, and subtraction imaging is helpful. Many MIBI avid thyroid lesions also accumulate pertechnetate and iodine, and subtraction reduces false positives. Single-photon emission computed tomography provides information for localizing parathyroid lesions, differentiating thyroid from parathyroid lesions, and detecting and localizing ectopic parathyroid lesions. The most frequent cause of false-positive MIBI results is the solid thyroid nodule. Other causes include thyroid carcinoma, lymphoma, and lymphadenopathy. False-negative results occur because of several factors. Lesion size is important. Cellular function also may be important. Parathyroid tissue that expresses P-glycoprotein does not accumulate MIBI. Parathyroid adenomas that express either P-glycoprotein or the multidrug resistance related protein MRP are less likely to accumulate MIBI. MIBI scintigraphy is less sensitive for detecting hyperplastic parathyroid glands. In secondary hyperparathyroidism, MIBI uptake is more closely related to cell cycle than to gland size. Mitochondria-rich oxyphil cells presumably account for MIBI uptake in parathyroid lesions. Fewer oxyphil cells, and hence fewer mitochondria, may explain both lower uptake and rapid washout of MIBI from some lesions. MIBI is also less sensitive for detecting multigland disease than solitary gland disease.

FDG PET of infection and inflammation.

Nuclear medicine plays an important role in the evaluation of infection and inflammation. Fluorine 18 fluorodeoxyglucose (FDG) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution tomography. In patients with acquired immunodeficiency syndrome, FDG positron emission tomography (PET) accurately helps localize foci of infection and is particularly useful for differentiating central nervous system lymphoma from toxoplasmosis. FDG PET can also help localize the source of fever of undetermined origin (FUO), thereby guiding additional testing. In the musculoskeletal system, FDG PET accurately helps diagnose spinal osteomyelitis, and in inflammatory conditions such as sarcoidosis and vasculitis, it appears to be useful for defining the extent of disease and monitoring response to treatment. FDG PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or a tumor. Nevertheless, this relatively new imaging technique promises to be helpful in the diagnosis of infection and inflammation. FDG PET will likely assume increasing importance in assessing FUO, spinal osteomyelitis, vasculitis, and sarcoidosis and may even become the radionuclide imaging procedure of choice in the evaluation of some or all of these pathologic conditions.

Regulation of hepatobiliary transport activity and noninvasive identification of cytokine-dependent liver inflammation.

UNLABELLED: Many diseases are associated with cytokine release after inflammatory infiltration, which perturbs organ function. Radioligands capable of noninvasive tracking to assess the integrity of specific biochemical pathways offer potent ways to establish such perturbing mechanisms. METHODS: To demonstrate regulation of hepatobiliary transport in disease, we used (99m)Tc-mebrofenin in a carbon tetrachloride-induced liver injury model in Fischer 344 rats. Healthy rats served as control animals. Image analysis was used to determine (99m)Tc-mebrofenin handling. Liver tests and histologic analysis were used for grading liver injury and hepatic fibrosis. To address the role of inflammatory cytokines, we used in vitro assays with (99m)Tc-mebrofenin-loaded primary rat hepatocytes. RESULTS: In healthy rats, (99m)Tc-mebrofenin was promptly excreted, and after 1 h only 20% +/- 5% (mean +/- SD) of peak (99m)Tc-mebrofenin activity remained in the liver. In contrast, rats treated with carbon tetrachloride for 1 or 3 mo showed 84% +/- 5% and 80% +/- 7% (mean +/- SD), respectively, of peak (99m)Tc-mebrofenin activity in the liver after 1 h (P < 0.001). Abnormal (99m)Tc-mebrofenin transport was associated with necroinflammatory activity and not hepatic fibrosis. This was examined directly in animals, where withdrawal of carbon tetrachloride for 2 wk after significant liver injury produced loss of inflammatory activity without affecting hepatic fibrosis. In this situation, (99m)Tc-mebrofenin transport returned to normal, indicating a central role of inflammatory activity in this process. In vitro assays showed impairment in (99m)Tc-mebrofenin excretion after incubation of cultured hepatocytes with interleukin-6 and further impairment with interleukin-6 plus tumor necrosis factor-alpha. CONCLUSION: The findings indicate that inflammatory cytokines regulate (99m)Tc-mebrofenin transport. This cytokine-mediated process establishes a paradigm for identifying and monitoring organ inflammation, including in viral or alcoholic hepatitis, fatty liver disease, allograft rejection, and responses to gene therapy vectors.

Coincidence-detection FDG-PET versus gallium in children and young adults with newly diagnosed Hodgkin's disease.

UNLABELLED: Coincidence-detection 18F-FDG-PET (PET) and 67Ga whole-body and SPECT (Ga) were compared in children and young adults with newly diagnosed Hodgkin's disease (HD). MATERIALS AND METHODS: Thirty patients with histologically confirmed HD underwent PET with attenuation correction 1 h after injection of 150-220 MBq 18F-FDG and whole-body and SPECT imaging 72 h after injection of 250-370 MBq 67Ga citrate. Two experienced readers retrospectively reviewed PET and Ga scans, grading 13 anatomic regions from one (normal) to five (abnormal). Numerical stages were assigned based on Ann Arbor classification. Comparison was made with disease sites (established by biopsy or two or more of the following: physical examination, conventional imaging studies, radionuclide studies, and follow-up studies) and clinical stages. Sensitivity, specificity, and accuracy were calculated and significance of differences determined using McNemar's test. RESULTS: PET detected 120/138 (87%) disease sites and Ga 109/138 (79%). PET and Ga were concordant for 103/138 (75%) sites. Accuracies were not significantly different for supradiaphragmatic disease. PET was more accurate than Ga for detecting splenic (0.91 vs 0.61, P = 0.012), infradiaphragmatic (0.89 vs 0.75, P = 0.042), and all disease sites combined (0.95 vs 0.91, P = 0.039). PET stage agreed with clinical stage in 79% of patients and Ga in 71%. CONCLUSION: PET was superior to Ga for evaluating children and young adults with newly diagnosed HD.

Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled leukocyte/99mTc-sulfur colloid marrow imaging.

UNLABELLED: The objectives of this study were to investigate (18)F-FDG imaging, using a coincidence detection system, for diagnosing prosthetic joint infection and to compare it with combined (111)In-labeled leukocyte/(99m)Tc-sulfur colloid marrow imaging in patients with failed lower extremity joint replacements. METHODS: Fifty-nine patients--with painful, failed, lower extremity joint prostheses, 40 hip and 19 knee--who underwent (18)F-FDG, labeled leukocyte, and bone marrow imaging, and had histopathologic and microbiologic confirmation of the final diagnosis, formed the basis of this investigation. (18)F-FDG images were interpreted as positive for infection using 4 different criteria: criterion 1: any periprosthetic activity, regardless of location or intensity; criterion 2: periprosthetic activity on the (18)F-FDG image, without corresponding activity on the marrow image; criterion 3: only bone-prosthesis interface activity, regardless of intensity; criterion 4: semiquantitative analysis--a lesion-to-background ratio was generated, and the cutoff value yielding the highest accuracy for determining the presence of infection was determined. Labeled leukocyte/marrow images were interpreted as positive for infection when periprosthetic activity was present on the labeled leukocyte image without corresponding activity on the marrow image. RESULTS: Twenty-five (42%) prostheses, 14 hip and 11 knee, were infected. The sensitivity, specificity, and accuracy of (18)F-FDG, by criterion, were as follows: criterion 1: 100%, 9%, 47%; criterion 2: 96%, 35%, 61%; criterion 3: 52%, 44%, 47%; criterion 4: 36%, 97%, 71%. The sensitivity, specificity, and accuracy of labeled leukocyte/marrow imaging were 100%, 91%, and 95%, respectively. WBC/marrow imaging, which was more accurate than any of the (18)F-FDG criteria for all prostheses, as well as for hips and knees separately, was significantly more sensitive than criterion 3 (P < 0.001) and criterion 4 (P < 0.001) and was significantly more specific than criterion 1 (P < 0.001), criterion 2 (P < 0.001), and criterion 3 (P < 0.001). CONCLUSION: Regardless of how the images are interpreted, coincidence detection-based (18)F-FDG imaging is less accurate than, and cannot replace, labeled leukocyte/marrow imaging for diagnosing infection of the failed prosthetic joint.