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Biomedical subjects

B L Shulkin

Publications and source records attributed to B L Shulkin.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

FDG PET imaging of paragangliomas of the neck: comparison with MIBG SPET.

Two patients with cervical paragangliomas underwent positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). There was marked tumor uptake and retention of FDG. Adjacent salivary gland accumulation of FDG was minimal, though quite prominent with meta-iodobenzylguanidine. FDG PET offers another potentially useful approach to functional imaging of these uncommon tumors, independent of the presence of specific amine uptake mechanisms or cell surface receptors required by other scintigraphic techniques.

3-Iodobenzylguanidine↗
PubMed1995

Inhibition of neutral amino acid transport across the human blood-brain barrier by phenylalanine.

The delivery of large neutral amino acids (LNAAs) to brain across the blood-brain barrier (BBB) is mediated by the L-type neutral amino acid transporter present in the membranes of the brain capillary endothelial cell. In experimental animals, the L-system transporter is saturated under normal conditions, and therefore an elevation in the plasma concentration of one LNAA will reduce brain uptake of others. In this study, we used positron emission tomography (PET) to determine the effect of elevated plasma phenylalanine concentrations on the uptake of an artificial neutral amino acid, [11C]-aminocyclohexanecarboxylate ([11C]ACHC), in human brain. PET scans were performed on six normal male subjects after an overnight fast and again 60 min after oral administration of 100 mg/kg of phenylalanine. The plasma phenylalanine concentration increased by an average of 11-fold between the first and second scans. This increase produced a reduction in [11C]ACHC uptake in all brain regions but not in scalp. The mean +/- SD influx rate constant for whole brain decreased after phenylalanine ingestion from 0.036 +/- 0.002 to 0.019 +/- 0.004 ml/g/min. Kinetic analysis of the effect of plasma phenylalanine concentration on the rate of [11C]ACHC uptake is compatible with a model of competitive inhibition so that large increases in the concentration of one LNAA in plasma will reduce the brain uptake of other LNAAs across the human BBB.

Adult↗
PubMed1995

Neoplasms in a pediatric population: 2-[F-18]-fluoro-2-deoxy-D-glucose PET studies.

PURPOSE: To assess the uptake of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in common and uncommon tumors in children and to develop a method for performing positron emission tomography (PET) studies in children with malignant neoplasms. MATERIALS AND METHODS: Twenty-two pediatric patients with known or suspected malignancies (27 scans) underwent FDG PET. Tumor uptake of FDG was measured on PET scans. RESULTS: Tumor uptake of FDG was detected in 17 of 21 patients with malignant disease. Neuroblastomas and their metastases (including those that did not absorb metaiodobenzylguanidine) intensely accumulated FDG. In a patient with Ewing sarcoma, FDG PET showed two foci of metastatic disease not evident on bone scans. In two patients, PET showed that large areas of the tumor were necrotic. CONCLUSION: FDG PET is feasible, is useful in the study of tumors in children, and may provide unique, clinically important information.

Adolescent↗
PubMed1994

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↗
PubMed1993

MIBG detection of hepatic neuroblastoma: correlation with CT, US and surgical findings.

Metaiodobenzylguanidine (MIBG) imaging is used in the diagnosis, staging and follow-up of virtually every case of neuroblastoma seen at our institution. Normal sites of MIBG uptake include the liver and therefore difficulties have been predicted and encountered in the diagnosis of hepatic neuroblastoma due to inability to separate abnormally increased tracer deposition from normal hepatic activity. We reviewed every MIBG (I123 and I131) study performed at our pediatric hospital over a 4 year period encompassing 88 patients, 67 of whom had biopsy proven neuroblastoma. Hepatic findings onMIBG studies were compared with concurrent abdominal CT and US studies in all 67 patients. The clinical records of all patients with abnormal MIBG scans or abnormal CT or US studies of the liver were also reviewed. Eight patients were found to have abnormal liver findings on one or more imaging studies (MIBG, CT, or US). There were 3 true positive MIBG studies, one of which was an early study in a patient who later went on to have one of the false positive studies. Two patients had false positive MIBG scans for liver neuroblastoma. MIBG failed to detect liver involvement in 4 patients.

3-Iodobenzylguanidine↗
PubMed1993

Pheochromocytomas that do not accumulate metaiodobenzylguanidine: localization with PET and administration of FDG.

Many imaging methods can be used to detect pheochromocytoma, but some tumors are not detected with conventional modalities. To explore the possible usefulness of positron emission tomography (PET) after administration of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) to localize pheochromocytoma in patients with false-negative scintigrams obtained after administration of metaiodobenzylguanidine (MIBG), FDG was administered and PET was performed in two adult patients with pheochromocytomas that had never been localized despite administration of MIBG. In both patients, images were obtained dynamically for 50 minutes; then a limited truncal sequence was performed. PET enabled correct localization of the tumors. In patient 1, a tumor that had not been detected for 21 years was localized in the middle mediastinum; in patient 2, a pheochromocytoma was detected in the right adrenal gland. PET performed after administration of FDG may be useful for localization of pheochromocytomas that do not accumulate MIBG.

3-Iodobenzylguanidine↗
PubMed1992

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↗
PubMed1992

Bilateral testicular neuroblastoma. Scintigraphic depiction and therapy with I-131 MIBG.

The authors describe a 29-year-old man who had a 16-year history of neuroblastoma and uncommon manifestations. At age 13, he was diagnosed with stage III retroperitoneal ganglioneuroblastoma that was resected. Ten years later, bilateral testicular enlargement and a pelvic mass from infiltration of the neuroblastoma became palpable. Metastatic involvement was depicted with MIBG, a radiotracer that concentrates in tissues of the sympathetic nervous system. Using I-131 MIBG, the tumors were treated with therapeutic doses of radiation and a partial response was obtained. This case is unique because of the massive degree of bilateral testicular infiltration and its occurrence as a late manifestation of neuroblastoma in early adulthood.

3-Iodobenzylguanidine↗
PubMed1992

Postprocedural symptoms in children who undergo imaging studies of the urinary tract: is it the contrast material or the catheter?

The frequency, nature, and duration of postprocedural symptoms in 100 children who underwent voiding cystourethrography (VCUG) after administration of 17.2% wt/vol iothalamate meglumine, 100 children who underwent radionuclide cystography (RNC) after administration of saline and technetium-99m pertechnetate, and 28 children catheterized before diuretic renal scintigraphy (DRS) were prospectively assessed with telephone follow-up. All children were aged 2 years or older; 61 were boys, 167 were girls. Postprocedural symptoms occurred in 80 children (35.1%). The frequency of postprocedural symptoms was nearly identical in the VCUG group and the two other groups. Boys (n = 33 [54%]) had symptoms significantly more often than girls (n = 47 [28%]) (P less than or equal to .0005). Dysuria was the most common symptom (n = 75 [32.9%]) and was frequently accompanied in younger children by anxiety over going to the bathroom. Symptoms disappeared within 24 hours in 32 of 80 children (40%) and lasted 4-10 days in eight children. It is concluded that most postprocedural symptoms in children who undergo VCUG, RNC, or DRS are secondary to catheterization rather than to the use of iodinated contrast material.

Child↗
PubMed1992

Iodine-131-metaiodobenzylguanidine and bone scintigraphy for the detection of neuroblastoma.

The purpose of this study was to compare the utility of bone and metaiodobenzylguanidine (MIBG) scintigraphy for the detection of primary and metastatic deposits of neuroblastoma. 99mTc methylene diphosphonate (MDP) bone and 131I-MIBG scans performed within 1 mo of each other in 85 patients with known or suspected neuroblastoma were evaluated for evidence of skeletal and extraskeletal disease. In 77 of 77 patients with confirmed neuroblastoma, the MDP and MIBG scans were concordant for the presence or absence of skeletal disease. A nearly twofold greater number of skeletal lesions were evident on MIBG scanning. No patients with normal bone scans had MIBG studies indicating bone involvement. In patients with histologic evidence of bone marrow involvement, each study suggested skeletal lesions in approximately 70%. In patients with extraskeletal disease demonstrated by CT, there was soft-tissue uptake of MIBG in 80% and MDP in 39%. We conclude that both MIBG and MDP are useful for the detection of skeletal neuroblastoma. MIBG is the better agent for characterizing the extent of disease, and MDP is a valuable adjunctive agent that provides skeletal landmarks for comparison. MIBG is clearly superior for the detection of extraskeletal neuroblastoma.

3-Iodobenzylguanidine↗
PubMed1992

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↗
PubMed1991

Flare response in Ewing's sarcoma.

A 3 1/2-year-old boy had thigh pain and a leg mass. Bone scanning demonstrated intense uptake within the involved femur, but no uptake within the soft tissues or evidence of metastatic spread. Radiographs and CT scanning showed a large soft tissue mass and periosteal reaction suggestive of Ewing's sarcoma. Following chemotherapy, the patient had an apparently good clinical response. However, bone scanning showed uptake that was more intense and extensive than it was before therapy. Plain films and CT showed that the uptake was evidence of soft tissue calcification and that the mass had shrunk. This is an unusual example of the flare response to therapy because the apparent progression of the disease on bone scanning was caused by extraskeletal uptake.

Antineoplastic Combined Chemotherapy Protocols↗