Normal values for sincalide cholescintigraphy: comparison of two methods.

PURPOSE: To establish normal gallbladder ejection fraction (GBEF) values for two sincalide (cholecystokinin [CCK]) infusion dose rates, 0.01 microg per kilogram of body weight infused for 3 minutes and 0.01 microg/kg infused for 60 minutes. MATERIALS AND METHODS: Twenty healthy subjects were examined. GBEFs were calculated for the 3-minute infusion and for each 15-minute interval for the 60-minute infusion. Normal values were determined by using the mean +/- 2 SDs and a more rigorous statistical analysis. RESULTS: With the 3-minute infusion, GBEFs were significantly more variable than with the 45- and 60-minute values for the 60-minute infusion (P < .01, .002). With intervals including 95% of the population, the GBEF lower normal range was 16.8% for the 3-minute infusion but 31% and 41% for the 45- and 60-minute values, respectively. GBEFs of less than 35% were noted in six (30%) of 20 healthy subjects with the 3-minute infusion but in only one with the 60-minute infusion. Hepatobiliary ultrasonography was performed in six of seven subjects with GBEF of 36% or less, and US findings in all six were normal. CONCLUSION: A 3-minute infusion of sincalide, 0.01 microg/kg, produces too variable a GBEF response to establish a clinically useful normal range. With 0.01 microg/kg infused for 60 minutes, clinically useful normal values were established at 45 and 60 minutes.

Cholecystokinin cholescintigraphy: clinical indications and proper methodology.

Cholecystokinin is a useful diagnostic adjunct to cholescintigraphy. Clinical indications include contracting the gallbladder before cholescintigraphy in patients fasting greater than 24 hours, during cholescintigraphy to diagnose sphincter of Oddi dysfunction, and after cholescintigraphy to exclude acute acalculous cholecystitis, differentiate common duct obstruction from normal variation, and to confirm the diagnosis of chronic acalculous cholecystitis. Proper methodology is mandatory for a diagnostically useful test. Data presented shows that a 3-minute infusion of 0.01 or 0.02 microg/kg is nonphysiologic and often results in ineffective contraction similar to that seen with a bolus infusion. Normal gallbladder ejection (GBEF) values cannot be established using a 3-minute infusion because of the wide variability in response. Instead, infusions of 30 or 60 minutes are required. Normal GBEF values have been established for these methods and are 30% and 40%, respectively.

Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin.

PURPOSE: To evaluate the safety, tolerability, and pharmacokinetics of biricodar (VX-710), an inhibitor of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP1), alone and with doxorubicin in patients with advanced malignancies. The effect of VX-710 on the tissue distribution of (99m)Tc-sestamibi, a P-gp and MRP1 substrate, was also evaluated. PATIENTS AND METHODS: Patients with solid malignancies refractory to standard therapy first received a 96-hour infusion of VX-710 alone at 20 to 160 mg/m(2)/h. After a 3-day washout, a second infusion of VX-710 was begun, on the second day of which doxorubicin 45 mg/m(2) was administered. Cycles were repeated every 21 to 28 days. (99m)Tc-sestamibi scans were performed before and during administration of VX-710 alone. RESULTS: Of the 28 patients who enrolled, 25 patients were eligible for analysis. No dose-limiting toxicity (DLT) was observed in the nine assessable patients who received 120 mg/m(2)/h or less. Among seven patients receiving VX-710 160 mg/m(2)/h, two DLTs were seen: reversible CNS toxicity and febrile neutropenia. All other adverse events were mild to moderate and reversible. Plasma concentrations of VX-710 in patients who received at 120 and 160 mg/m(2)/h were two- to fourfold higher than concentrations required to fully reverse drug resistance in vitro. VX-710 exhibited linear pharmacokinetics with a harmonic mean half-life of 1.1 hours. VX-710 enhanced hepatic uptake and retention of (99m)Tc-sestamibi in all patients. CONCLUSION: A 96-hour infusion of VX-710 at 120 mg/m(2)/h plus doxorubicin 45 mg/m(2) has acceptable toxicity in patients with refractory malignancies. The safety and pharmacokinetics of VX-710 plus doxorubicin warrant efficacy trials in malignancies expressing P-gp and/or MRP1.

Cholecystokinin cholescintigraphy: victim of its own success?

Numerous publications have reported that a low gallbladder ejection fraction (GBEF) determined by cholecystokinin (CCK) cholescintigraphy has a high positive predictive value for the diagnosis of chronic acalculous cholecystitis (CAC). Clinicians and surgeons have found this test to be clinically useful as an objective method to confirm their clinical diagnosis. However, an abnormally low GBEF is not specific for CAC. For example, numerous other diseases have been associated with a low GBEF, and various therapeutic drugs can cause poor gallbladder contraction. Importantly, improper CCK infusion methodology can result in an erroneously low GBEF. More than one third of healthy subjects and patients who receive sincalide, 0.02 microg/kg infused over 1-3 min, will have an erroneously low GBEF but will have a normal GBEF with a slower infusion (30-60 min) of the same total dose. Because of enthusiastic acceptance of CCK cholescintigraphy by clinicians, the types of patients referred for this test have changed over time. Patients investigated in publications confirming the usefulness of CCK cholescintigraphy had a high pretest likelihood of disease. They underwent extensive workup to rule out other diseases and were followed up for months or years before CCK cholescintigraphy was performed, allowing other diseases to become manifest or symptoms to resolve. However, CCK cholescintigraphy is now being used by clinicians to shorten the workup and follow-up time based on the rationale that CCK cholescintigraphy can quickly confirm or exclude the diagnosis. This new group of referral patients has a lower likelihood of the disease. Many will ultimately be diagnosed with diseases other than CAC. The positive predictive value of this test will likely be lower and the false-positive rate will likely be higher. Nuclear medicine physicians must work to minimize false-positive studies to maintain the confidence of referring clinicians. First, we can educate referring physicians as to the proper use of this study. Next, we must perform CCK cholescintigraphy using optimal methodology that will result in the lowest possible false-positive rate. And finally, we must interpret CCK cholescintigraphy in light of the patient's history, prior workup and clinical setting.

Technetium-99m-sestamibi parathyroid scintigraphy: effect of P-glycoprotein, histology and tumor size on detectability.

UNLABELLED: The purpose of this study was to evaluate the effect of P-glycoprotein (P-gp) levels, predominant histology and tumor size on the detectability of parathyroid adenomas with 99mTc-sestamibi scans. Although previous studies have shown that positivity correlates with tumor size, false-negative studies have been reported with large tumors and true-positives reported with very small tumors. Recent investigations have reported rapid washout of sestamibi in malignant tumors because of high levels of P-gp, similar to that seen with multidrug chemotherapy resistance. Therefore, we postulated that this mechanism might account for false-negative studies in parathyroid tumors. Preliminary reports have suggested that the predominant histological subtype influences positivity on 99mTc-sestamibi parathyroid scans. METHODS: We studied 25 patients with surgically confirmed parathyroid adenomas with 99mTc-sestamibi parathyroid scans. The results of the imaging study were correlated with tissue P-gp levels, predominant histological subtype and size of the surgically removed glands. RESULTS: There were 21 true-positive and 4 false-negative results. The size of the adenomas ranged from 0.12 to 8.64 ml. We found no correlation between the results of the dual-phase 99mTc-sestamibi study and either the predominant cell type or the level of P-gp. Positivity did correlate with the size of the adenoma (p=0.73, p < 0.0001). We cannot exclude the possibility that P-gp and cell type may still play a role in individual cases, but we suspect that other yet to be determined factors may influence 99mTc-sestamibi detectability in addition to tumor size.

Gastrointestinal symptoms and delayed gastric emptying in Fabry's disease: response to metoclopramide.

The pathophysiology of gastrointestinal symptoms in patients with Fabry's disease is uncertain, despite the demonstration of histological and radiographic abnormalities of the gastrointestinal tract. The aims of this study were to determine if the gastrointestinal symptoms reported by patients with Fabry's disease are associated with abnormal gastric emptying and, if they are, whether prokinetic drug therapy would be beneficial. Ten patients with Fabry's disease had radionuclide gastric emptying studies performed to determine if gastrointestinal symptoms correlated with objective evidence of abnormal gastric emptying. A second study was performed in seven patients who received 5 days of therapy with oral metoclopramide. The mean percent solid gastric emptying for Fabry's patients was significantly less than that of a normal control group (40 vs 67%, P < 0.005). Five of seven patients with symptoms had abnormal gastric emptying. Six of seven symptomatic patients reported clinical improvement with metoclopramide. Of four symptomatic patients who had a repeat study after treatment, two showed improved emptying. In conclusion, our results suggest that gastrointestinal symptoms in Fabry's disease are frequently associated with delayed gastric emptying and that treatment with metoclopramide produces symptomatic and sometimes functional improvement.

Lag phase quantification for solid gastric emptying studies.

UNLABELLED: This study compared the different calculation methods of the solid gastric emptying lag phase and evaluated the effect of the temporal sampling interval on the calculated value using the modified power exponential (MPE) method. METHODS: Twenty normal control subjects and 42 patients had anterior and posterior image acquisition on a multihead gamma camera, one frame per minute x 90. ROIs were selected for the stomach, gastric antrum and small bowel. Time-activity curves (TACs) were generated for anterior, posterior and geometric mean data. The lag phase was calculated using various methods such as transition point, starting index, first appearance of bowel activity (FABA), MPE and antral peak filling time. To determine the importance of the temporal sampling rate on the calculation of the lag phase by the MPE, intervals between 1 and 20 min were analyzed. RESULTS: The transition point, starting index and FABA correlated extremely high (r = > or = 0.92) in normal control subjects and patients. Normal lag phase values were mean 22-24 +/- 10 min for transition point, starting index and FABA compared with 47 +/- 18 min for the MPE method (p < 0.0001). The MPE correlated poorly with the other method (r = 0.74). Antral peak filling time correlated poorly (r = 0.47) with transition point, starting index and FABA, but somewhat better with the MPE (r = 0.70). Comparing 15-min versus 1-min sampling intervals using the MPE, 35% of subjects had values that differed by > or = 7.5 min and 10% had values differing by > or = 15 min. CONCLUSION: The lag phase calculated by the MPE correlated poorly with other methods, and its accuracy was limited by the rate of the temporal sampling. The transition point, starting index and FABA all highly correlated with each other; the latter is a particularly reliable physiological indicator and is easily quantified using a small-bowel TAC.

Frequency of extra-cardiac activity and its effect on 99Tcm-MIBI cardiac SPET interpretation.

There are limited published data concerning the frequency and relative intensity of abdominal activity on 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) myocardial perfusion scans and its effect on interpretation. We undertook a blinded prospective study to evaluate (1) the frequency and intensity of abdominal activity on single photon emission tomography (SPET) scans, (2) its effect on separate evaluation of rest and stress SPET images, and (3) its effect on clinical interpretation. Patients undergoing one-day rest-stress 99Tcm-MIBI scans were randomized to receive 99Tcm-MIBI obtained from one of two radiopharmacies. The rest plus exercise or rest plus intravenous dipyridamole scans of 303 patients were scored separately by three physicians for (1) intensity of abdominal activity and (2) its effect on scan evaluation. Nuclear reports generated independently of the blinded evaluation were reviewed to assess the effect of abdominal activity on clinical interpretation. There were no statistical differences between pharmacies. Abdominal activity was uncommon on the exercise but common on the rest and dipyridamole scans. The exercise scans differed from the rest and dipyridamole scans in the subgroups: intensity of abdominal activity equal to myocardium, and greater than myocardium (P < 0.001). There was no difference between the rest and dipyridamole scans. The effect on evaluation was moderate in 5% of the exercise, 46% of the dipyridamole and 37% of the rest scans, and severe in 1% of the exercise, 3% of the dipyridamole and 12% of the rest scans. Rest differed from exercise (P < 0.001) and from dipyridamole (P < 0.05). There was no difference between the dipyridamole and exercise scans. Based on the clinical reports, abdominal activity was a limitation to scan interpretation for 20 patients; in 5, the inferior wall could not be evaluated. Although abdominal activity was frequently observed on both the dipyridamole and rest scans, it was a limitation to clinical interpretation in a small fraction of the patients.

Comparison of Tc-99m MIBI and TI-201/Tc-99m pertechnetate for diagnosis of primary hyperparathyroidism.

The purpose of this study was to directly compare the efficacy of Tc-99m MIBI with TI-201/Tc-99m pertechnetate scintigraphy for localizing parathyroid adenomas in patients with primary hyperparathyroidism. Of 21 patients suspected of having primary hyperparathyroidism who had undergone both studies, 14 had subsequent surgery and pathologic correlation. Based on the surgical and pathologic results, Tc-99m MIBI yielded 13 true-positive and 1 false-negative result. Thallium-201/ Tc-99m pertechnetate imaging yielded eight true-positive, four false-negative, and two nondiagnostic studies because of lack of Tc-99m pertechnetate uptake from thyroid hormone suppression. In conclusion, Tc-99m MIBI scintigraphy is an accurate method for localizing parathyroid adenomas in patients with primary hyperparathyroidism and the results suggest that it is superior to using TI-201/Tc-99m pertechnetate.

Positive technetium-99m-red blood cell gastrointestinal bleeding scan after barium small-bowel study.

A 53-yr-old man with hepatic insufficiency and portal hypertension was hospitalized and underwent a work-up for gastrointestinal bleeding requiring multiple transfusions. The initial evaluation included a negative upper and lower endoscopy and a barium exam of the small bowel. Both studies failed to demonstrate any pathology to explain the bleeding. Immediately following the barium study, the patient had active bleeding. Because of the significant amount of intestinal barium, angiography was deferred. Technetium-99m-red blood cell (RBC) scintigraphy was undertaken to identify the site of bleeding. Despite intestinal barium, the 99m-Tc-RBC scan demonstrated an active bleeding site in the small bowel in the left abdomen. Therefore, 99mTc-RBC scintigraphy can be of clinical utility for identification of gastrointestinal bleeding, despite the presence of intestinal barium.

Therapy dose calculation in Graves' disease using early I-123 uptake measurements.

A retrospective study was performed to assess the feasibility of using the 4-hour I-123 early uptake value in the calculation of the treatment dose of radioactive iodine in Graves' disease patients. The Graves' disease patients were randomly divided into two groups. Data from the first group of 35 patients were used to obtain a regression relationship between the early 4-hour uptake (EUp) and 24-hour late uptake values (LUp). This equation, LUp = -38.618 + 65.216 Log (EUp) was used to estimate the predicted late uptake (PUp) from (EUp) in the second group of 34 patients. LUp was used to calculate the I-131 therapy dose for treatment in these patients. In 28 clinically euthyroid patients, the 4-hour uptake I-123 radioactive iodine uptake (RAIU) ranged from 7% to 20% (mean, 12 +/- 3.5%). In 60 Graves' disease patients, the 4-hour RAIU ranged from 15% to 100% (mean, 57 +/- 24.8%). Of these, there were five patients with a normal 4-hour uptake, but elevated 24-hour uptake. LUp correlated well with PUp (r = 0.81162), as did the dose calculation based on predicted and observed 24-hour uptake values (r = 0.82204). Thus, same day measurement of uptake and treatment of Graves' disease is feasible.

Atlas of iodocholesterol scintigraphy (NP-59) in Cushing's syndrome with CT and MR correlation.

An atlas of I-131 iodocholesterol scintigraphy, each with correlative CT or MRI illustrates the findings in 12 patients with biochemically proven Cushing's syndrome and ultimate surgical cure. Included are patients with both ACTH dependent and independent disease, as well as patients with postoperative functional adrenal remnants. Emphasis will be on the concordance or discordance of the anatomical and functional imaging modalities.

Role of preoperative iodocholesterol scintiscanning in patients undergoing adrenalectomy for Cushing's syndrome.

BACKGROUND: Iodocholesterol scintiscanning (IS) is a noninvasive, functional diagnostic test. We report our experience with IS as an adjunct for adrenal surgery for Cushing's syndrome. METHODS: Between April 1983 and October 1994, 23 patients with Cushing's syndrome from benign primary adrenal disease underwent IS and computed tomography (CT) and/or magnetic resonance imaging (MRI). Twelve patients had unilateral adrenal involvement with a solitary adenoma (n = 11) or unilateral multinodular disease (n = 1), and 11 patients had bilateral adrenal disease. RESULTS: In patients with Cushing's syndrome caused by unilateral adrenal disease, IS was 100% specific and 100% sensitive, whereas in two cases CT/MRI incorrectly showed bilateral disease. In patients with Cushing's syndrome with bilateral adrenal involvement, IS had one false-negative result with nonvisualization. CT/MRI showed unilateral disease in four cases and no abnormalities in two. All patients in this series were cured of Cushing's syndrome after unilateral adrenalectomy in 11 cases and bilateral adrenalectomy in 12 cases. CONCLUSIONS: IS is a highly sensitive and specific imaging modality and is an essential adjunct to biochemical testing in planning adrenal resections for Cushing's syndrome caused by primary adrenal disease.

Diagnosis of intracranial lymphoma in patients with AIDS: value of 201TI single-photon emission computed tomography.

OBJECTIVE: Although the prevalence of intracranial lymphoma is high among patients with AIDS, current imaging techniques are not reliable for differentiating this tumor from other common nonneoplastic lesions, such as those seen in toxoplasmosis. The purpose of this study was to prospectively investigate the use of 201Tl single-photon emission computed tomography (SPECT) in identifying intracranial lymphoma in patients with AIDS. SUBJECTS AND METHODS: Thirteen patients with AIDS and intracranial masses underwent 201Tl imaging with a three-headed SPECT camera. Sic of the 13 were subsequently proved to have lymphoma. Studies were interpreted prospectively as showing tumor if uptake of 201Tl was increased in the region where the lesion was seen on MR images. A lesion-to-nonlesion uptake ratio (counts/pixel) was calculated retrospectively. RESULTS: The SPECT images of six patients were interpreted prospectively as showing no lymphoma. Uptake ratios in these six patients were 0.77-1.95 (mean, 1.45). In each, tumor was excluded as a final diagnosis (four had toxoplasmosis, one had progressive multifocal leukoencephalopathy, and one had venous angioma). Among the seven patients with SPECT images interpreted as showing lymphoma, six were later proved to have lymphoma (uptake ratio: mean, 3.65; range, 2.95-4.30; p < .005). The SPECT findings in the seventh patient were classified as false-positive for tumor on the basis of the prospective interpretation of the images; three concurrent infections were found at autopsy. The uptake ratio in this patient was low (1.81), suggesting that quantification might have diagnostic usefulness for improving accuracy. CONCLUSION: This preliminary study indicates that 201Tl SPECT might be a useful, noninvasive method for differentiating intracranial lymphoma from nonneoplastic lesions in patients with AIDS.

Quantitation of renal function using radioisotopic techniques.

Radioisotopic methods are practical for clinical use because they do not require continuous intravenous infusion or urine collection. This obviously is of great advantage in infants and small children, in whom accurate urine collection is difficult, but the techniques apply to adults as well. The ability to determine individual kidney function is a major benefit. Accuracies of the radioisotopic techniques vary but generally are within clinically acceptable ranges. The need for accuracy and reproducibility can be balanced with the desire for speed and convenience when choosing among the different techniques. Methods that use plasma sampling provide greater accuracy and are recommended in cases of severe dysfunction, whereas methods such as Gates' camera method, which eliminates plasma samples, can be completed in minutes. Radioisotopic techniques are most useful in the ranges of mild to moderately decreased function, in which serum creatinine concentration is nondiagnostic, and although they are much less accurate at markedly low renal function levels, so is 24-hour creatinine clearance. In conclusion, radiopharmaceutical agents offer a wide array of possible techniques for simple, accurate, and noninvasive measurement of global as well as individual GFR and ERPF.

Tc-99m MAG3 as an alternative to Tc-99m DTPA and I-131 Hippuran for renal transplant evaluation.

This study investigated the new radiopharmaceutical, Tc-99m mercaptoacetyltriglycine (MAG3), as a possible alternative to Tc-99m DTPA and I-131 Hippuran for renal transplant evaluation. Tc-99m MAG3 and I-131 Hippuran were used sequentially in 19 consecutive patient studies and compared qualitatively and quantitatively. Serum creatinine values ranged from 1.6 mg/dL to 10.3 mg/dL (mean, 5.4 mg/dL). The Tc-99m MAG3 images and time-activity curves were of superior quality (3+) compared to I-131 Hippuran (1-2+). Quantitative analysis of the time to peak activity (Tmax) demonstrated a high correlation and no significant difference for Tc-99m MAG3 (mean, 11.4 min) compared to I-131 Hippuran (mean, 11.2 min). The percentage of peak activity retained at 20 minutes (T20) also showed a high correlation between the two agents; however, Tc-MAG3 showed a significantly slower clearance (T20 mean, 77%) than I-131 Hippuran (mean, 71%). Flow images were judged to be of good quality; however, the first-pass time-activity curves were often different from that seen with Tc-99m DTPA. Interpretation of delayed Tc-99m MAG3 images, for example to diagnose a slow urinary leak, were sometimes complicated by bowel clearance. In conclusion, Tc-99m MAG3 is superior to I-131 Hippuran for evaluation of renal transplant function. Tc-99m is the agent of choice for evaluation of renal transplant blood flow and function.