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J C Sisson

Publications and source records attributed to J C Sisson.

At least 37 records · Page 2Linked to original sources

131-I treatment of micronodular pulmonary metastases from papillary thyroid carcinoma.

BACKGROUND: 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. METHODS: Of 232 patients treated with 131-I for thyroid carcinoma between 1985 and 1994, 12 patients between the ages of 5 and 45 years exhibited evidence of micronodular metastases to the lungs that concentrated 131-I. Each patient had undergone total or nearly total thyroidectomy and cervical lymph node dissection. All neoplasms were well differentiated papillary carcinoma, but one also had focal, poorly differentiated insular components. Follicle formation by tumors varied from less than 10% to 100% of the histologic sections. Effects of treatment were measured by three indices: chest X-ray and/or CT images, scintigraphic images, and serum thyroglobulin levels. Individual activities of 131-I ranged from 2.2 gigabequerel (GBq) (initial activity in the 5-year-old patient) to 13 GBq, and were greater than 7.4 GBq in 6 patients. Only one treatment was given to three patients, two were given to seven, and more than two were given to two. The duration of follow-up was at least one year. RESULTS: In two patients, the only evidence of lung metastases was on scintigraphic images made a few days after treatment. Another patient had a normal X-ray but showed diffuse uptake of 131-I in the lungs on a diagnostic scintiscan. Of the nine patients with abnormal X-ray and CT images, seven showed improvement, but tumors disappeared in only two. In the ten patients with abnormalities on the diagnostic scintiscans, five eventually manifested no abnormality. At the outset, thyroglobulin levels exceeded 10 ng/mL in each patient; 3 individuals exhibited a decline in level by 25% or more, and a value of less than 6 ng/mL, uncomplicated by thyroglobulin antibodies, was seen in two patients. Only two patients attained normality in all three indices. Hematologic toxicity was modest and reversible. CONCLUSIONS: Despite a number of previous reports that pulmonary metastases from thyroid carcinoma disappear in approximately half of patients treated with 131-I, evidence of tumor reduction was found in most, but a complete remission occurred in only 2 of 12 patients. Nevertheless, 131-I therapy may be useful to decrease the tumor burden in many such patients.

Adolescent↗

Survival of patients with neuroblastoma treated with 125-I MIBG.

Recurrent or persistent neuroblastoma in stages III and IV is usually fatal despite modern therapies. Metaiodobenzylguanidine labeled with 131-I (131-I MIBG) concentrates in most neuroblastoma and when given in doses that impart therapeutic radiation, has produced remissions in patients with these tumors. However, success with 131-I MIBG has been limited. The physical characteristics of radiation imparted by 125-I MIBG theoretically could overcome some of the limitations that restrain the therapeutic effects of 131-I MIBG in patients with neuroblastoma. Thereby, 125-I MIBG may offer advantages over 131-I MIBG in the treatment of neuroblastoma. Ten children who manifested persistent/recurrent stage III or IV neuroblastoma were given 8.3 to 30.1 GBq or 224 to 814 mCi of 125-I MIBG in a phase I-II trial. Five of the patients had progression-free survivals > 1 year (continuing in three patients), and four of these subjects are surviving 17 to 52 months after treatment with 125-I MIBG. With appropriate doses of 125-I MIBG, life-threatening toxicity can be avoided. Thus, survivals after 125-I MIBG appear to be as long or longer than those historically observed following other treatments for patients similarly afflicted with refractory neuroblastoma.

3-Iodobenzylguanidine↗

Neuroblastoma: positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose compared with metaiodobenzylguanidine scintigraphy.

PURPOSE: To assess the uptake in neuroblastoma of 2-[fluorine-18] -fluoro-2-deoxy-D-glucose (FDG) versus metaiodobenzylguanidine (MIBG). MATERIALS AND METHODS: Seventeen patients with known or suspected neuroblastoma underwent FDG positron emission tomography (PET) (20 scans) and MIBG scintigraphy. Tumor uptake of FDG was quantified on positive PET scans. RESULTS: Tumor uptake of FDG was detected in 16 of 17 patients (18 of 20 scans). Neuroblastomas and their metastases avidly concentrated FDG prior to chemotherapy or radiation therapy. Uptake after therapy was variable. Uptake of FDG was intense in one patient with neuroblastoma that failed to accumulate MIBG. In 13 of the 20 scans, however, MIBG was rated superior to FDG for delineation of tumor compared with background and normal organs. CONCLUSION: Most neuroblastomas accumulate FDG. The mechanism of MIBG uptake is more intense prior to therapy. Concentration of FDG is not dependent on type 1 catecholamine uptake. FDG PET helps define the distribution of neuroblastomas that fail to concentrate MIBG.

3-Iodobenzylguanidine↗

PET hydroxyephedrine imaging of neuroblastoma.

UNLABELLED: The goals of this investigation were to characterize the uptake of 11C-hydroxyephedrine (HED) in neuroblastoma and to determine the feasibility and potential advantages of utilizing this compound as a tumor imaging agent. METHODS: Seven patients with known or subsequently proven neuroblastoma were studied. Each patient underwent PET scanning with 11C-HED. Six of seven patients underwent scintigraphy with [123I]meta-iodobenzylguanidine (MIBG), and two patients were also studied with [18F]FDG PET. For six patients, CT or MR images were available for comparison. RESULTS: Neuroblastomas were located by PET scanning with 11C-HED in all seven patients. The uptake of HED into neuroblastomas was rapid; tumors were evident on images within 5 min postintravenous injection. Those lesions in the field of view of the PET camera were also identified on [123I]MIBG scintigraphic images. In two patients, tumor deposits in the abdomen were better visualized with MIBG scintigraphy due to relatively less hepatic accumulation of MIBG than HED. CONCLUSION: PET scanning with HED for neuroblastoma results in high quality functional images of the tumors that can be obtained within minutes following injection.

3-Iodobenzylguanidine↗

Iodine-123-MIBG imaging of neuroblastoma: utility of SPECT and delayed imaging.

UNLABELLED: Possible incremental diagnostic benefits of SPECT and delayed planar imaging with [123I]MIBG in neuroblastoma have not yet been fully established. METHODS: Whole-body delayed planar [123I]MIBG imaging at 48 hr and SPECT imaging of the chest-abdomen or other suspected sites obtained at 24 hr were compared with routine planar imaging at 24 hr in 83 studies of 29 children with neuroblastoma. The sensitivity for each of the [123I]MIBG imaging methods was calculated on a study-by-study and on a lesion-by-lesion basis. RESULTS: Fifty-one planar imaging studies were performed in 20 patients with evidence of disease which was detected in 48 studies by 24-hr imaging (94.1% sensitivity) and in 44 studies by 48-hr imaging (86.3% sensitivity). On a lesion-by-lesion basis, sensitivity was 88.8% for the 24-hr scan, 86.7% for the 48-hr scan and 92.2% for a combination of the two (p = ns). Forty-three SPECT studies were performed in 20 patients with evidence of disease in the field of view of the SPECT camera. Disease was detected in 40 SPECT studies (93% sensitivity), in 38 planar scans at 24 hr (84.4% sensitivity) and in 37 planar scans at 48 hr (86.0% sensitivity). On a lesion-by-lesion basis, sensitivity was 83.6% for the 24-hr planar scan, 86.1% for the 48-hr planar scan, 88.2% for a combination of the two planar scans and 97.9% for SPECT (p < 0.001 compared with planar). The anatomic locations of tumors were clearer on SPECT in 15 studies. CONCLUSION: Delayed 48-hr planar scanning may occasionally depict more lesions than 24-hr imaging, but it may also miss lesions with rapid washout. SPECT imaging significantly increases the number of lesions detected and better defines anatomic location of tumors.

3-Iodobenzylguanidine↗

Simultaneous scintigraphic depiction of aldosteronoma and adrenal infarction.

Primary aldosteronism is a potentially curable cause of hypertension, especially when caused by an adrenal adenoma. Aldosteronomas because of their small size often elude techniques to locate them. This case illustrates the advantages, disadvantages and complications of noninvasive techniques used for their diagnosis. A patient with hypertension and hypokalemia underwent an adrenal venous effluent sampling for measurement of aldosterone concentrations. This procedure was complicated by an injury to the right adrenal gland. Subsequently, it was difficult to control the patient's hypertension and hypokalemia with medical therapy alone. A re-assessment years after his initial diagnosis included a CT scan, which now visualized a left adrenal tumor. The functional status of this tumor and lack of function of the previously injured right adrenal gland were demonstrated by NP-59 scintigraphy. This information modified the surgical intervention (adenectomy rather than total adrenalectomy) and the residual left sided adrenal tissue prevented adrenocortical insufficiency. A year later the patient remains euadrenal.

Adosterol↗

The current status of meta-iodobenzylguanidine and related agents for the diagnosis of neuro-endocrine tumors.

Metaiodobenzylguanidine (MIBG) has been in clinical use for 15 years and has been shown to have high sensitivity (about 85%) and specificity (> 95%) for the location of all types of pheochromocytomas. Similar results have been achieved with neuroblastomas. A wide range of other neuroendocrine lesions including carcinoids, medullary thyroid cancer and nonsecretory paragangliomas may also be imaged, but the lower sensitivity. The newly developed radiolabeled somatostatin analogs may have greater utility for these lesions. MIBG scintigraphy may also provide a unique in vivo probe for study of the sympathetic autonomic nervous system, particularly in the heart. Various radiolabels for MIBG and its analogs permit planar scintigraphy, SPECT, PET, intraoperative probe localization and radiopharmaceutical therapy.

3-Iodobenzylguanidine↗

The current status of radioiodinated metaiodobenzylguanidine therapy of neuro-endocrine tumors.

The avidity of many metastatic pheochromocytomas and neuroblastomas for metaiodobenzylguanidine (MIBG) observed at diagnostic scintigraphy has led to attempts to treat these lesions with large doses of MIBG. We and others have achieved therapeutic responses with 131I-MIBG (usually partial) in about a third of malignant pheochromocytomas. A small but important subgroup of advanced, poor prognosis neuroblastomas which have been resistant to all other therapies have also shown responses including occasional long-term survival (> 5 years) and apparent complete responses to 131I-MIBG. Because the physical properties of 131I are suboptimal for the delivery of therapeutic radiation to bone marrow micrometastases, a frequent problem in neuroblastoma, we have performed preliminary studies in poor prognosis Stage III and VI neuroblastoma using 125I-MIBG which has more satisfactory emissions. This has led to prolonged tumor stabilization and survival (> 19 to > 52 months) in 5 of 10 patients. MIBG radiopharmaceutical treatment of neuroendocrine tumor patients must still be considered an experimental but nevertheless promising treatment modality.

3-Iodobenzylguanidine↗

Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine.

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131I-MIBG (4.9-8.1 GBq or 132-220 mCi) and ten were given 125I-MIBG (8.3-30.0 GBq or 224-809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131I-MIBG; GBq/kg of body weight; and GBq/m2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131I-MIBG, the highest correlation was obtained between cGy and the log10-transformed platelet ratio (r = -0.86), but comparison of GBq/m2 and the platelet nadir (r = -0.76) or the platelet ratio (r = -0.74) or the log10 transformed platelet ratio (r = -0.73) gave comparable and statistically significant results. For treatments with 125I-MIBG, significant correlations were obtained between GBq/m2 and the platelet ratio (r = -0.81) or GBq/kg and the log10-transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131I-MIBG was 2.6 times more potent than 125I-MIBG in causing a platelet ratio of 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Locating neuroblastoma in the opsoclonus-myoclonus syndrome.

We examined the role of various medical imaging modalities, particularly metaiodobenzylguanidine (MIBG) scintigraphy in the investigation of patients presenting with the opsoclonus-myoclonus syndrome (OMS) who may harbor neuroblastomas. A retrospective analysis was therefore performed of all patients presenting with OMS in a 5 1/2 year period. Between December, 1988 and May, 1994, all 13 patients (mean age 15.2 months, range 3 days-30 months) presenting with OMS were extensively studied. A wide range of medical imaging modalities including CT, MRI and [131I] or [123I]-metaiodobenzylguanidine (MIBG) scintigraphy (total of 21 scans) were examined as a means of detecting a structural brain lesion or locating a neuroblastoma, a tumor generally found in less than half of patients with OMS. As anticipated a minority of patients (4) were eventually found to harbor neuroblastomas. In these four cases, two tumors were revealed on preoperative MIBG scintigraphy, one gave a false negative study and one tumor was not studied preoperatively. Each patient was also subjected to extensive radiological investigations in addition to MIBG scintigraphy, many of which were repetitive, redundant or had low clinical yield. The relative merits of the various procedures are compared, and an algorithm incorporating MIBG scintigraphy and limited central nervous system and abdominal anatomical modalities for the investigation of opsoclonus-myoclonus is suggested.

3-Iodobenzylguanidine↗

Autoradiography-based, three-dimensional calculation of dose rate for murine, human-tumor xenografts.

A Fast Fourier Transform method for calculating the three-dimensional dose rate distribution for murine, human-tumor xenografts is outlined. The required input includes evenly-spaced activity slices which span the tumor. Numerical values in these slices are determined by quantitative 125I autoradiography. For the absorbed dose-rate calculation, we assume the activity from both 131I- and 90Y-labeled radiopharmaceuticals would be distributed as is measured with the 125I label. Two example cases are presented: an ovarian-carcinoma xenograft with an IgG 2ak monoclonal antibody and a neuroblastoma xenograft with meta-iodobenzylguanidine (MIBG). Considering all the volume elements in a tumor, we show, by comparison of histograms and also relative standard deviations, that the measured 125I activity and the calculated 131I dose-rate distributions, are similarly non-uniform and that they are more non-uniform than the calculated 90Y dose-rate distribution. However, the maximum-to-minimum ratio, another measure of non-uniformity, decreases by roughly an order of magnitude from one distribution to the next in the order given above.

Animals↗

Uptake of 18-fluoro-2-deoxy-D-glucose by thyroid cancer: implications for diagnosis and therapy.

A patient developed a pulmonary metastasis from papillary thyroid carcinoma. This tumor concentrated relatively little 131I, but sufficient 18F-fluoro-2-deoxy-D-glucose (FDG) to be quantified and imaged by positron emission tomography. The uptake of FDG was lower on positron emission tomographic images after T4 therapy and when the serum TSH concentration was reduced to the low normal range. It may be possible to use decreases in FDG uptake by thyroid cancers, which represent declines in metabolism by the tumors, to indicate the optimum doses of T4 treatment for patients with these neoplasms. In addition, the ratio of tumor to background radioactivity was higher for FDG than for the flow agent 201Tl, so that studies with FDG may be a useful scintigraphic method for locating thyroid cancers when radioiodine imaging is unsatisfactory.

Carcinoma, Papillary↗

131-I-metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma.

Fourteen patients with refractory advanced neuroblastoma were treated with 131-I-metaiodobenzylguanidine (131-I-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated.

3-Iodobenzylguanidine↗

Learning, retention and recall of clinical information.

A representative group of 33 medical students who were entering the junior year clerkships was tested for retention and recall of clinical information 3 months after taking an examination on the same subject. The students were not given an opportunity to review the subject. On 39 identical multiple choice test questions, the students' mean score declined 10 percentile points (P < 0.05) from that on the original examination. On 40 comparable but previously unseen questions, the mean score fell 19 percentile points from that attained 3 months earlier. On open-ended questions of clinical reasoning, a third component of the assessment, the students performed at a level similar to those on the two multiple choice tests, but with greater variability. These assessments give data on retention and recall that have not previously been reported in the literature. Correlations among individual test components were moderate (r = 0.52-0.63). There was inconsistency of individual students in scores on the component tests, and, thus, variability in performance by students was marked. Retention and recall were weakly predicted by results on an initial multiple choice examination. In addition, on a subsequent assessment of knowledge, results from different types of tests were inconsistent, suggesting that these tests evaluate different forms of competence.

Clinical Clerkship↗

PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma.

Pheochromocytomas are potentially curable causes of hypertension. These tumors are currently located by functional imaging with meta-iodobenzylguanidine (MIBG), usually labeled with 131I, or anatomic imaging (computed tomography, magnetic resonance). Hydroxyephedrine (HED) is a newly developed radiotracer that concentrates in adrenergic nerve terminals. When HED is labeled with 11C, its distribution can be mapped in vivo using PET. The purposes of this investigation were to characterize the uptake of 11C-HED in pheochromocytoma and to determine the feasibility and advantages of utilizing this compound as a tumor imaging agent. Ten patients with known or suspected pheochromocytoma were studied. Each patient underwent PET scanning with 11C-HED and conventional scintigraphy with MIBG. Pheochromocytomas were localized by PET scanning in 9 of the 10 patients. Image quality was excellent and superior to that obtained from planar and tomographic MIBG studies. The uptake of 11C-HED into pheochromocytomas was rapid; tumors were evident within 5 min following intravenous injection. All lesions within the field of view that were identified by MIBG scintigraphy were readily apparent. PET scanning with 11C-HED localizes pheochromocytoma using a specifically designed radiotracer and advanced imaging technology. The method has promise for locating the more elusive tumors.

3-Iodobenzylguanidine↗