Milton D. Gross

Scintigraphic Localization of Pheochromocytoma

We used a new radiopharmaceutical agent, [131I]meta-iodobenzylguanidine ([131I]MIBG), to produce scintigraphic images of pheochromocytomas in eight patients. One day or more after injection, the only normal organ that displayed distinct concentrations of radioactivity was the urinary bladder. The [131I]MIBG was probably concentrated in adrenergic vesicles; in tissues where vesicles are numerous, such as pheochromocytomas, the radionuclide was retained for days. The spectrum of pheochromocytomas shown the scintigrams was broad: intra-adrenal and extraadrenal in location, benign and malignant in character, 0.2 to 65 g in weight, and with different hormone patterns in secretion. Tumors in four patients were not detected by computed tomography. In one patient, reoperation was undertaken only because the scintigram located the extra-adrenal tumors and thereby directed the surgeons exploration. The method offers hope of safe and reliable localization of pheochromocytomas in their many guises.

Impaired left ventricular contractile function in patients with long-term mitral regurgitation and normal ejection fraction☆☆☆

OBJECTIVES We tested the hypotheses that left ventricular chamber elastance would detect impaired contractile function in patients with long-term mitral regurgitation and a normal ejection fraction and that these patients would have unique temporal left ventricular size and ejection fraction responses to mitral valve surgery. BACKGROUND Although it has been suggested that left ventricular contractile function may begin deteriorating in patients with long-term mitral regurgitation whereas ejection fraction remains normal, no data exist in humans. METHODS We studied 11 control patients and 28 patients with long-term mitral regurgitation using micromanometer-measured pressures, biplane contrast cineventriculography and radionuclide angiography under control conditions and with alterations in load during right atrial pacing to calculate left ventricular chamber elastance and myocardial stiffness. RESULTS The patients with mitral regurgitation were classified into subgroups: Group I, normal contractile function; Group II, impaired contractile function (reduced Emax) but normal ejection fraction, and Group III, impaired contractile function (reduced Emax) with reduced systolic myocardial stiffness. Twenty-two of the patients with mitral regurgitation underwent mitral valve surgery. In Group I, comparable decreases in left ventricular volume indexes (p < 0.01 and p = 0.05, respectively) were associated with no change in ejection fraction at 3 months and 1 year. In contrast, in Group II, reductions in volume indexes (p < 0.0001 and p < 0.001) were associated with a short-term decrease in ejection fraction (p < 0.001) that recovered at 1 year (p < 0.01 vs. short-term). Finally, in Group III, variable responses in volume indexes were associated with a consistent decrease in ejection fraction at 3 months and 1 year. CONCLUSIONS An analysis of left ventricular chamber elastance provides data to support the concepts that 1) contractile function is impaired in some patients with long-term mitral regurgitation and a normal ejection fraction, 2) impaired contractile function may not be irreversible in all of these patients, and 3) an earlier consideration of mitral valve surgery may be warranted to preserve contractile function in these patients.

Androgen deprivation therapy for prostate cancer results in significant loss of bone density

OBJECTIVES Advanced prostate cancer is a frequently diagnosed condition in the aging male population, and many men will ultimately be treated with androgen deprivation therapy (ADT). Long-term consequences of ADT on bone mineral density (BMD) have not been systematically studied. We performed a pilot study to test the hypothesis that ADT in patients with prostate cancer results in the measurable loss of BMD. METHODS A cross-sectional study of 32 men with prostate cancer who were about to begin ADT or who had been receiving ADT for more than 1 year was conducted. BMD was measured by single and dual energy x-ray absorptiometry in the lumbar spine, hip, and forearm. Linear regression analysis was used to estimate the time necessary to develop significant BMD loss in the spine, hip, and forearm regions. RESULTS Five (63%) of 8 men who had not received ADT and 21 (88%) of 24 men who had received ADT for more than 1 year fulfilled the BMD criteria for osteopenia or osteoporosis at one or more sites. When BMD was compared at each site, men who received ADT for more than 1 year had significantly lower BMD in the lumbar spine than men who had not started treatment (P<0.05). On the basis of regression analysis, an estimated 48 months of ADT would be necessary to develop BMD criteria for osteopenia in the lumbar spine for a man with average BMD at the initiation of therapy. CONCLUSIONS Pre-existing osteopenia and osteoporosis were common in men with prostate cancer before initiating ADT. Both ADT and the duration of ADT were significantly associated with the loss of BMD in men with prostate cancer.

Positron emission tomography detects evidence of viability in rest technetium-99m sestamibi defects.

OBJECTIVES The purpose of this study was to determine the relative value of single-photon emission computed tomographic (SPECT) imaging at rest using technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with positron emission tomography for detection of viable myocardium. BACKGROUND Recent studies comparing positron emission tomography and thallium-201 reinjection with rest technetium-99m sestamibi imaging have suggested that the latter technique underestimates myocardial viability. METHODS Twenty patients with a previous myocardial infarction underwent rest technetium-99m sestamibi imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia activity (expressed as percent of peak activity) in nine cardiac segments and in the perfusion defect defined by the area having technetium-99m sestamibi activity < 60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of peak activity) and severe (< 50% of peak activity). Estimates of perfusion defect size were compared between technetium-99m sestamibi and N-13 ammonia. RESULTS Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments with severe defects had > or = 60% F-18 deoxyglucose activity considered indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still present in 50% of segments with technetium-99m sestamibi activity < 40%. There was no significant difference in the mean (+/- SD) technetium-99m sestamibi activity in segments with viable (40 +/- 7%) and nonviable segments (49 +/- 7%, p = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that measured by N-13 ammonia. The difference in defect size between technetium-99m sestamibi and N-13 ammonia was significantly greater in patients with viable (21 +/- 9%) versus nonviable segments (7 +/- 9%, p = 0.007). CONCLUSIONS Moderate and severe rest technetium-99m sestamibi defects frequently have metabolic evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion defects than does N-13 ammonia positron emission tomography when the same threshold values are used.

Using Fluorodeoxyglucose Positron Emission Tomography to Assess Tumor Volume During Radiotherapy for Non-Small-Cell Lung Cancer and Its Potential Impact on Adaptive Dose Escalation and Normal Tissue Sparing

PURPOSE To quantify changes in fluorodeoxyglucose (FDG)-avid tumor volume on positron emission tomography/computed tomography (PET/CT) during the course of radiation therapy and examine its potential use in adaptive radiotherapy for tumor dose escalation or normal tissue sparing in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS As part of a pilot study, patients with Stage I-III NSCLC underwent FDG-PET/CT before radiotherapy (RT) and in mid-RT (after 40-50 Gy). Gross tumor volumes were contoured on CT and PET scans obtained before and during RT. Three-dimensional conformal RT plans were generated for each patient, first using only pretreatment CT scans. Mid-RT PET volumes were then used to design boost fields. RESULTS Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, and 2 patients had slightly increased FDG uptake in the adjacent lung tissue. Mid-RT PET scans were useful in the 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range, +15% to -75%) and 44% (range, +10% to -100%), respectively. Designing boosts based on mid-RT PET allowed for a meaningful dose escalation of 30-102 Gy (mean, 58 Gy) or a reduction in normal tissue complication probability (NTCP) of 0.4-3% (mean, 2%) in 5 of 6 patients with smaller yet residual tumor volumes. CONCLUSIONS Tumor metabolic activity and volume can change significantly after 40-50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive RT are ongoing.

Radionuclide diagnosis and therapy of thyroid cancer: current status report

Thyroid cancer is uncommon, with an incidence of 10,300 new patients each year and a mortality of 1,100 patients each year. Patient survival correlates with many factors, including tumor pathology, age, primary lesion size, distant metastases, extent of surgery, and radioiodine therapy. Deaths from thyroid cancer may occur many years after diagnosis, and such an indolent course has hampered the analysis of the multiple treatment programs advocated. Thyroid imaging continues to play an important role in the initial detection and follow-up management of thyroid cancer, but the search for a specific tracer for the primary lesion continues. The complementary role of serum thyroglobulin and radioiodine in the follow-up of the thyroidectomized patient is discussed. Radioiodine therapy has proven effectiveness in those patients with radioiodine-avid distant metastases and/or regional metastases. Whether radioiodine ablation of residual thyroid bed activity is beneficial remains controversial.

Spectrum of Pheochromocytoma in Multiple Endocrine Neoplasia: A Scintigraphic Portrayal Using 131I-Metaiodobenzylguanidine

Six patients with multiple endocrine neoplasia (MEN) types 2a and 2b were investigated to determine the spectrum of pheochromocytoma by scintigraphy. Iodine-131-metaiodobenzylguanidine (131I-MIBG), a new imaging agent which concentrates in adrenergic neurotransmitter vesicles, was administered at 0.5 mCi/1.7m2 and scintiscans were taken at 24 and 48 hours. Two normotensive patients with normal plasma and urinary catecholamines had no adrenal tracer uptake. One patient with a modest and intermittent increase only in urinary catecholamine metabolites showed faint adrenal images. Two other patients with increased plasma and urinary catecholamines showed bilateral adrenal imaging patterns. The sixth patient who had increased norepinephrine and epinephrine secretion showed bilateral asymmetrical adrenal images, findings that were corroborated at operation. Functional as well as anatomic evidence of adrenal medullary abnormalities in patients with MEN-2 syndromes are demonstrated by 131I-MIBG scintigraphy. Therefore, the procedure can be used to define the extent of abnormalities of the adrenal medulla in these patients.

Comparative study of coronary flow reserve, coronary anatomy and results of radionuclide exercise tests in patients with coronary artery disease

A comparative assessment of regional coronary flow reserve, quantitative percent diameter coronary stenosis and exercise-induced perfusion and wall motion abnormalities was performed in 39 patients with coronary artery disease. Coronary flow reserve was determined by a digital angiographic technique utilizing contrast medium as the hyperemic agent. Percent diameter stenosis was calculated by an automated quantification program applied to orthogonal cineangiograms. Thallium-201 scintigraphy and radionuclide ventriculography were used to assess regional perfusion and wall motion abnormalities, respectively, at rest and during exercise. In Group A, 19 patients without transmural infarction or collateral vessels, coronary flow reserve was inversely related to percent diameter stenosis (r = -0.61, p less than 0.0001), and scintigraphic abnormalities occurred only in vascular distributions with a coronary flow reserve of less than 2.00. There was a strong relation among abnormal regional exercise results, stenoses greater than 50% and reactive hyperemia of less than 2.00. Patients with multivessel disease, however, often had normal exercise scintigrams in regions associated with greater than 50% stenosis and low coronary flow reserve when other regions had a lower coronary flow reserve or higher grade stenosis, or both. In Group B, 20 patients with angiographically visible collateral vessels, 12 of whom had prior myocardial infarction, coronary flow reserve correlated less well with percent diameter stenosis than in Group A (r = -0.47, p less than 0.004). As in Group A patients, there was a significant relation between abnormal exercise test results and stenoses greater than 50%. However, reactive hyperemia values were generally lower than in Group A, and positive exercise stress results were strongly correlated only with highly impaired flow reserves of 1.3 or less. In Group B patients, the coronary flow reserve of vessels with less than 50% stenosis was significantly lower than that of similar vessels in Group A patients (2.40 +/- 0.79 versus 1.56 +/- 0.43; p less than 0.0002). It is concluded that: there is a general relation between quantitative percent diameter stenosis and reactive hyperemia that is not of sufficient precision to allow accurate prediction of coronary flow reserve in individual cases; exercise scintigraphic abnormalities are usually associated with low coronary flow reserve, and the relation between these two functional tests is stronger than the relation between exercise test results and quantitative percent diameter stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)

131‐I treatment of micronodular pulmonary metastases from papillary thyroid carcinoma

Pulmonary metastases from papillary thyroid carcinoma shorten the survival of the hosts. Treatments with 131‐I have been reported to induce disappearance of these tumors in a large proportion of afflicted patients. In this study, consecutive patients with diffuse micronodular lung metastases from papillary thyroid carcinoma were examined to determine if disappearance of tumor occurred, and how much disappeared, after substantial amounts of 131‐I were administered.

Dual PET/CT with 18F-DOPA and 18F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: Comparison with conventional imaging

BACKGROUND To evaluate the role of a multi-imaging PET with (18)F-DOPA and (18)F-FDG in comparison with conventional imaging (CI) in recurrent medullary thyroid carcinoma (MTC). METHODS 18 MTC patients who had thyroidectomy were included; they presented with elevated and rapidly increasing calcitonin levels during follow up. CI had revealed metastatic deposits in 9 patients. Patients were referred to us for a PET/CT with (18)F-DOPA and (18)F-FDG. Histologic/cytologic confirmation of recurrent MTC was obtained in at least one PET-positive lesion in all patients. RESULTS Foci of abnormal uptake were observed in 15 patients at (18)F-DOPA and in 11 at (18)F-FDG; 8 patients showed the same number of positive lesions with both tracers, 2 showed more lesions on (18)F-FDG, 1 was positive at (18)F-FDG alone and 5 at (18)F-DOPA alone. In 3 patients with a DOPA-positive loco-regional relapse a re-operation with curative intent was offered. SUV(max) values were higher for (18)F-FDG compared to (18)F-DOPA (mean 12.7+/-4.1 vs. 5.5+/-2.1, p<0.05). Calcitonin was higher in PET-positive patients compared to PET negative ones, while no significant differences were observed between (18)F-DOPA and (18)F-FDG positive patients. CONCLUSIONS In MTC patients with rapidly increasing calcitonin levels during follow up, (18)F-DOPA has a good sensitivity and a complementary role with (18)F-FDG PET/CT in detecting metastatic deposits. In our experience, the sensitivity of a multi-imaging (18)F-DOPA &(18)F-FDG PET/CT approach is greater than that obtained with CI. The higher SUV(max) values found with (18)F-FDG in some patients may reflect more aggressive tumors.