Reevaluation of the impact of a stringent low-iodine diet on ablation rates in radioiodine treatment of thyroid carcinoma.

Prior analyses of the impact of stringent, preablative low-iodine diets (LIDs) on ablation in patients with differentiated thyroid cancer postthyroidectomy are dated. We retrospectively reviewed first-time, short-term ablation rates for 44 LID patients and 50 patients following a regular diet (RD) who were verbally instructed to avoid salt, seafood, and multivitamins containing iodine. Patients who had undergone ablation were given between 100 and 200 mCi of 131I, depending on the presence of metastases. We found a 68.2% ablation rate for LID patients, compared to a 62.0% rate for RD patients, a nonsignificant difference (p = 0.53). We observed a dose-response relationship for both patient groups, with higher ablation rates corresponding to higher doses of radioiodine administered. We also measured iodine levels in spot urine samples from 7 matched LID patients and 7 matched RD adherents (healthy volunteers) prediet and postdiet as well as 39 healthy volunteers. LID patients had a lower mean urinary iodine level postdiet (173.9 microg/L; range, 45-1,217 microg/L; standard deviation [SD] = 127.7) than the RD patients (mean, 381.4 microg/L; range, 140-630 microg/L; SD = 196.3) or the 39 normal controls (444.0 microg/L; range, 50-1,690 microg/L; SD = 413.4). Whereas the LID lowered urinary iodine levels by 69.4% from prediet values, the RD reduced urinary iodine by 23.6%. Although differences in the reduction of urinary iodine levels between the LID and the RD were substantial, both groups experienced equivalent outcomes. The level of iodine in the American diet has progressively decreased, and may be much lower now than when prior LID studies were conducted. We suggest that prescribing a refined, less stringent diet that avoids high-iodine-containing foods would offer equivalent outcomes with increased patient convenience.

The nonimpact of thyroid stunning: remnant ablation rates in 131I-scanned and nonscanned individuals.

Thyroid stunning has been reported as the temporary impairment of thyroid tissue after a 111-MBq or greater diagnostic 131I dose that decreases the final absorbed dose in ablative therapy. Concerns regarding the reality of stunning have arisen in part due to a flawed study design in prior reports. To assess whether a stunning effect has any impact on therapeutic outcomes, we compared initial treatment ablation rates in patients who received 111- to 185-MBq 131I diagnostic scans (n = 37) before ablative doses of 3700-7400 MBq with ablation rates in patients who did not receive any 131I before the initial treatment dose (n = 63). Ablation rates were 64.9% for scanned patients and 66.7% for nonscanned patients, a nonsignificant difference. Nonscanned patients with metastatic lesions (n = 23) were ablated at a higher rate (78.3%) than scanned patients (n = 9) (66.7%), but the difference was not significant (P = 0.50). It is possible that the reported stunning phenomenon, specifically its impact in temporarily impairing tissue, has been overemphasized.

Accuracy considerations when using early (four- or six-hour) radioactive iodine uptake to predict twenty-four-hour values for radioactive iodine dosage in the treatment of Graves' disease.

Although literature has offered methods to predict 24-hour radioactive iodine uptake values from early (4- to 6-hour) measurements, the resultant dosage errors have not been examined. Potential errors include underdosage, overdosage, and a failure to recognize rapid turnover patients (early-to-late uptake ratios > or = 1) who are at high risk for treatment failure and full-body radiation exposure. We developed and tested a novel method for minimizing error involved in using a single early uptake measurement to derive late uptake. From a retrospective analysis of 203 Graves' disease patients, receiver operating characteristic (ROC) curve analysis enabled us to identify patients likely to experience rapid turnover and therefore should receive 24-hour studies. Twenty-four-hour uptake measurements are necessary with 77% or more 4-hour uptake values and 80% or more 6-hour values. After eliminating these patients, we developed linear regression equations to predict the 24-hour uptake from 4-hour (n = 61) and 6-hour (n = 22) rule groups, testing their efficacy on separate 4-hour (n = 61) and 6-hour (n = 21) patient groups. We also used our test population to measure error in four early-to-late uptake conversion formulas presented in the literature. Error involved in these predictions ranged from a 10.6% overestimate for 4-hour calculations to a 5.9% underestimate for 6-hour calculations. When applied to two dosage formulas incorporating gland size, absorbed dose, and 24-hour uptake, average dosage error was 7%. In comparison to the other sources of error radioactive iodine (131I) dosimetry, potential error in predicting 24-hour uptake from 4- or 6-hour uptake values is low.

Functional brain imaging in the assessment of multiple chemical sensitivities.

The author provides a brief overview of single photon emission computed tomography in the assessment of multiple chemical sensitivities.

Comparison of Technetium-99m sestamibi and indium-111 octreotide imaging in a patient with Ewing's sarcoma before and after stem cell transplantation.

BACKGROUND: We report the use of two novel nuclide agents, Technetium-99m (99Tc)sestamibi (MIBI) and indium-111 (In-111) octreotide, in comparison with conventional computed tomography (CT) imaging in a patient with metastatic Ewing's sarcoma (ES) before and after high dose chemotherapy with autologous peripheral stem cell transplantation (PSCT). MIBI is taken up actively by metabolically active tumor cells. Octreotide, a somatostatin analog, binds specifically to somatostatin receptors. METHODS: The patient was a 20-year-old male with recurrent metastatic ES to the lung. Before and sequentially after high dose chemotherapy and PSCT, the patient was imaged with MIBI. Whole body planar and single photon emission computed tomography (SPECT) images were obtained after the injection of 30 mCi of 99Tc MIBI. Prior to PSCT the patient was imaged with 6 mCi In-111 pentreotide. RESULTS: Conventional CT scans also were performed. Initial CT revealed pulmonary metastasis in the right lower lobe along with multiple left pleural-based lesions. These lesions were visualized clearly with MIBI. Octreotide detected only the left lung involvement. Sequential MIBI scans after PSCT correlated with tumor reduction in the right lung field and tumor progression in the left lung as well as the development of new pulmonary metastasis. These findings were confirmed on CT. CONCLUSIONS: MIBI imaging was highly concordant with CT scanning in the detection of metastatic ES. MIBI scanning holds promise for the direct detection of a variety of human malignancies, and may prove useful as a rapid whole body imaging modality.

Tumor quantitation and monitoring in whole-body planar technetium-99m-sestamibi imaging.

UNLABELLED: We have developed a completely automatic software package to normalize, rigidly register and elastically match serial whole-body planar images from patients with limb tumors. Variations in tumor uptake and size are analyzed and quantitated by the software. METHODS: The software consists of a chain of modules incorporating several automatic algorithms. A rigid registration algorithm aligns images by translation and rotation based on feature points corresponding to the patient's neck and bladder. An elastic matching algorithm generates a grid for each image in a sequence by combining thresholding and local feature analysis in the head, torso and leg regions. A linear warping algorithm then interpolates pixel values and locations to make the grid points in all images coincide with the grid points of one of them (the reference image). All images in a sequence are normalized based on brain uptake. Quantitation of tumor uptake and size is performed in all images using an ROI automatically determined from a single user-selected seed point. RESULTS: The software was tested on four 2-image and one 3-image sequences from five patients (11 images). Quantitative measurements of body contour overlap show an average intrasequence agreement of 73.4%, 78.7% and 91.5% for unregistered, rigidly registered and rigidly registered + matched images, respectively. CONCLUSION: Our method represents an objective, quantitative tool to measure tumor activity in sequential whole-body scintigraphic images, and may help assess tumor response to chemotherapy or radiation therapy.

The role of (99m)Tc methoxyisobutylisonitrile in imaging breast cancer.

Multiple imaging modalities have been used in evaluating patients suspected of breast cancer. Mammography and ultrasound are the dominant modalities now used by most mammographers. Mammography has been shown to be inaccurate in patients with dense breast or in breasts where significant architectural distortion has occurred. Alternative modalities independent of breast density are currently being evaluated. These include ultrasonography, magnetic resonance imaging, and nuclear medicine techniques. Recent reports indicate methoxyisobutylisonitrile (MIBI) to be promising in the evaluation of patients with difficult to evaluate mammograms. The current sensitivity and specificity figures for MIBI scintigraphy of the breast are dependent on a number of factors. A recent multicenter trial involving 673 patients sponsored by the DuPont-Merck Radiopharmaceutical Corporation indicated an overall sensitivity of 85% with a specificity of 81%. Nonpalpable lesions showed a sensitivity of 55% to 72%. The acceptance of MIBI breast imaging will be dependent on specific applications in which MIBI can be shown to be superior to alternative modalities. A promising subgroup of patients includes patients with dense breasts, breasts with architectural distortions, or extensive scaring from prior biopsies, especially if these patients are considered to be in a high risk category.

Technetium-99m sestamibi scanning in multiple myeloma stem cell transplantation.

We report the use of technetium-99m sestamibi (MIBI) in a patient with multiple myeloma (MM) undergoing peripheral blood stem cell (PBSC) transplantation. MIBI is a radionuclide agent that is preferentially taken up by malignant tumors. Plain radiographs in a MM patient, taken prior to PBSC transplantation, showed a large right humeral lytic lesion that correlated with increased uptake of MIBI at the same location. MIBI uptake, demonstrating active MM bone disease, was also evident in areas which were normal on plain radiographs. Three months after PBSC transplant, the lytic lesion had healed by plain radiographs and repeat MIBI scan showed no uptake. MIBI scanning results have a positive correlation with plain radiographs, and more importantly, demonstrate active MM bone disease not yet detectable by plain radiographs. If MIBI proves more sensitive in the detection of MM bone disease than plain radiographs or bone scanning with traditional isotopes, it will have a significant role in the detection of early disease and in monitoring disease progression during and after therapy.

Comparison of gallium-67-citrate and thallium-201 scintigraphy in peripheral and intrathoracic lymphoma.

UNLABELLED: We performed this study in an attempt to reconcile the differences with respect to 67Ga uptake as a function of tumor grade and type in the literature, as well as to determine the sensitivity of 201Tl uptake in both Hodgkin's and non-Hodgkin's lymphoma. METHODS: Thirty-six (9 with low-grade lymphoma, 11 with intermediate-grade lymphoma, 4 with high-grade lymphoma and 12 with Hodgkin's lymphoma) patients underwent both 67Ga and 201Tl scintigraphy. Biopsies were done on all patients. A semiquantitative rating system was used to make statistical comparisons for thallium versus gallium in all lymphoma subgroups, as well as comparisons of thallium and gallium to themselves in all subgroups. RESULTS: Patient sensitivity was only 56% and site sensitivity was 32% in patients with low-grade lymphoma. Conversely, 201Tl sensitivity was 100%, respectively, for patients and sites. The difference between 201Tl and 67Ga sensitivity in patients with low-grade lymphoma on a site basis was statistically significant. When compared to itself in lymphoma subgroups, 201Tl was found to be statistically more avid for low-grade lymphoma than for intermediate, high or Hodgkin's lymphoma. Gallium-67 sensitivity for low-grade lymphoma was significantly less than for Hodgkin's and intermediate grade lymphomas. No significant differences were found when 201Tl and 67Ga were compared in the intermediate, high or Hodgkin's lymphoma groups. CONCLUSION: Thallium-201 demonstrates significantly greater tumor avidity in the low-grade lymphoma group compared to 67Ga citrate. Gallium-67-citrate appears relatively nonavid for low-grade lymphoma compared to 201Tl and is statistically inferior in detecting low-grade lymphoma in comparison to its ability to detect intermediate or high-grade lymphomas. Gallium-67-citrate should not be considered dependable in evaluating patients with low-grade lymphoma. Neither 201Tl or 67Ga is dependable in the evaluation of low-grade lymphoma within the abdomen, since gallium avidity for low-grade lymphoma is low and gastrointestinal excretion of 201Tl is poorly controlled.

Technetium-99m Sestamibi Scanning Reflects Marrow Activity in a ß-Thalassemia Patient Treated with an Allogeneic Bone Marrow Transplant.

ß-thalassemia major is a disorder of globin synthesis, resulting in anemia and compensatory bone marrow hyperproliferation. Conventional imaging studies do not measure bone marrow activity reliably. We report on the use of technetium-99m sestamibi (MIBI) in a ß-thalassemia major patient treated with an allogeneic bone marrow transplant. Pre-transplant and early post-transplant MIBI scannings demonstrated generalized marrow uptake, reflecting marrow hyperproliferation. After full engraftment, post-transplant MIBI showed disappearance of abnormal uptake in the skeleton, indicating normalization of the marrow activity. MIBI scan may be used as a noninvasive measure of bone marrow proliferation that may guide hypertransfusion therapy in thalassemia patients.

Isogravitational heterogeneity of perfusion after unilateral lung transplantation.

1. Single-photon emission computerized tomography in both an intact canine model and man has demonstrated an aspect of pulmonary perfusion to be independent of gravitational forces. 2. Using technetium 99m-labelled macroaggregated albumin single-photon emission computerized tomographic imaging, we investigated normal human subjects (n = 5), stable unilateral lung transplant recipients (n = 6) and transplant recipients with chronic allograft dysfunction related to obliterative bronchiolitis (n = 5). 3. In coronal isogravitational sections, a 1 x 1 x N pixel strip (medial to lateral) was constructed through the 'core' pixel of maximal radioactive counts. The counts were measured for the 'core' pixel and at two mid-points (medial and lateral) between the core pixel and the lung edges. Coefficients of variation were computed for each isogravitational strip and compared between groups. Fractional whole-lung perfusion was determined for left versus right lungs of normal subjects and allograft versus native lungs of transplant recipients. 4. Using these indices, 'isogravitational heterogeneity' (i.e. increased 'core' versus peripheral perfusion) was observed in allografts and native diseased lungs after unilateral transplantation. Despite significantly increased fractional whole-lung perfusion directed to the allografts (84.8% +/- 3.0% and 75.8% + 12.1% for stable unilateral lung transplant recipients and patients with obliterative bronchiolitis respectively) compared with normal lungs (50.2% +/- 1.2% and 49.8% +/- 1.2% for left and right respectively), 'isogravitational flow heterogeneity' (i.e. increased 'core' versus peripheral perfusion) was preserved after transplantation. 5. These findings suggest that 'isogravitational heterogeneity' was maintained despite increased unilateral pulmonary perfusion and the presumed increase in pulmonary capillary recruitment and/or distension.

The safety and pharmacokinetics in adult subjects of an intravenously administered 99mTc-labeled 17 amino acid peptide (CYT-379).

A phase I study was designed to evaluate the safety and pharmacokinetics of a novel platelet reactive peptide, peptide acetyl-SYGRGDVRGDFKCTCCA-amide (CYT-379), which binds to the fibrinogen receptor of activated platelets and also binds to 99mTc. Eleven subjects with suspected deep venous thrombosis had 0.1, 0.5 or 1.0 mg of the peptide infused intravenously. Pharmacokinetics were determined by assaying blood samples in 6 of the 11 subjects and by urine sampling in 5 of these 6 subjects. Plasma and whole blood time-activity curves demonstrated an initial fast component with half-time clearance of 0.2 +/- 0.01 and 0.2 +/- 0.02 h and a slow component with half-time clearance of 2.8 +/- 0.3 and 2.7 +/- 0.2 h (mean +/- SEM for plasma and whole blood, respectively). Urine clearance was 22.6 +/- 3.3 and 10.8 +/- 1.6 mL/min when normalized to body surface area. The cumulative excretion of 99mTc-CYT-379 in the urine was 16.6 +/- 3.6, 45.6 +/- 16.9 and 45.6 +/- 1.8% of the administered dose over 0-2, 0-12 and 0-24 h after radiopharmaceutical injection, respectively. Images obtained in 11 subjects immediately, at 1-2, and 4-6 h after injection were evaluated for abnormalities and were compared with duplex Doppler ultrasonography. 99mTc-CYT-379 images were positive in only 3 of 7 subjects who had a positive duplex Doppler examination in at least one lower extremity. One subject with negative duplex Doppler had also negative 99mTc-CYT-379 scintigraphy. One subject with negative scintigraphy and two other subjects with positive scintigraphy had no other imaging studies of the deep venous system performed. No adverse reactions were observed during or after the infusion of 99mTc-CYT-379. 99mTc-CYT-379 appears to be a safe radiopharmaceutical and demonstrates rapid clearance from plasma in human subjects.

The rim sign in acute cholecystitis. Comparison of radionuclide, surgical, and pathologic findings.

Nonvisualization of the gallbladder associated with the rim sign of enhanced pericholecystic hepatic activity has been established as a useful and highly specific sign of acute cholecystitis. This study's purpose was to determine the pathophysiologic cause of the rim sign. Thirty-seven surgery-bound patients with a clinical diagnosis of acute cholecystitis were studied. A group of 20 patients with a definite rim sign were compared to a group of 17 patients without a rim sign; all with nonvisualization of the gallbladder. Radionuclide, surgical, and pathologic findings were correlated. In patients with the rim sign and in those without the rim sign, microscopic review of all surgical specimens revealed transmural reaction of the gallbladder wall in 95% and 59% of cases, respectively. The surgeon found inflammation extending beyond the gallbladder wall in 75% of rim sign cases, but in only 35% of case without the rim sign. Liver tissue was attached to the gallbladder specimen in three cases, and the findings support the association of hepatic inflammation with the presence of a rim sign. Pathologic correlation and surgical evidence suggest that the rim sign is caused by the spread of inflammation through the gallbladder wall and into adjacent liver tissue. Transmural reaction is required before the inflammatory process can reach the liver. A high-count, high-intensity technique seems to best demonstrate the rim sign. Once demonstrated, further delayed imaging is unnecessary.

Regional distribution of lung perfusion and ventilation at rest and during steady-state exercise after unilateral lung transplantation.

Cardiopulmonary exercise testing has previously demonstrated a reduced maximum oxygen uptake and anaerobic threshold, as well as abnormal wasted ventilation fraction and gas exchange after unilateral lung transplantation. To further explain the mechanisms of these abnormalities, we assessed the regional distribution of pulmonary blood flow and ventilation at rest and during steady-state exercise in nine recipients of unilateral lung transplants. Krypton-81 (81mKr) aerosol and technetium-99m (99mTc) were utilized to assess lung ventilation (V) and perfusion (Q), respectively. The digitalized images were trisected to analyze apical, mid-, and basilar lung perfusion and ventilation in both the transplanted and native lung, both at rest and steady-state upright exercise. Results were compared with previously reported data obtained in normal subjects in our laboratory using the identical technique. At rest, 75 +/- 13 percent of perfusion was directed to the transplanted lung; however, the corresponding fractional ventilation was only 67 +/- 14 percent. During exercise, there was no significant change in fractional perfusion or ventilation. Resting apical perfusion in the transplanted lung was higher than normal in four patients and comparable to normal in five patients. In contrast to the augmentation of apical perfusion observed in normal subjects during upright exercise, none of our patients increased the regional perfusion to the apices during exercise in either transplanted or native lungs. These unexpected responses suggest either more maximal allograft apical recruitment at rest due to the increased allograft perfusion or an abnormality in the apical pulmonary vasculature after transplantation. Furthermore, the relative mismatch in ventilation and perfusion in transplanted and native lungs suggests regions of high V/Q in the native, and low V/Q in the transplanted lung. This mismatch is most pronounced in recipients of single lung transplants for pulmonary vascular disease.

Thallium scintigraphy in the evaluation of mass abnormalities of the breast.

Palpable mass abnormalities of the breast are often difficult to evaluate mammographically, especially in patients with fibrocystic change and dense breasts. The current study evaluates 201TI scintigraphy as a potential test in detecting malignancy and in differentiating malignant from benign masses. Eighty-one female patients underwent thallium scintigraphy of the breast because of palpable breast masses. An additional 30 females with no palpable breast abnormalities were also studied using 201TI. Of 44 patients with palpable breast carcinomas, 42 carcinomas (96%) were detected using 201TI scintigraphy. Three of three patients had other primary breast malignancies that were also detected. In contrast, 19 patients with palpable breast abnormalities shown on biopsy to be benign fibrocystic disease processes were not detectable on thallium studies. Of two patients with fat necrosis, none were detectable. Three of 13 patients had adenomas of the breast (23%) that were detected. The three detectable adenomas were all highly cellular. The smallest detectable carcinoma was an adenocarcinoma measuring 1.3 x 1.1 x 0.9 cm. Thallium-201 scintigraphy of palpable breast lesions is an effective test for evaluation of palpable masses. Sensitivity for detection of malignant masses greater than 1.5 cm is high. Highly cellular adenomas, however, may demonstrate significant 201TI uptake. Benign fibrocystic disease is not detectable with thallium scintigraphy. Thallium scintigraphy of breast lesions is an effective means of differentiating benign from malignant lesions.

Use of thallium 201 in tumor evaluation.

The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in nuclear medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in nuclear medicine that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Nuclear Medicine of the California Medical Association, and summaries were prepared under its direction.