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Biomedical subjects

B Shapiro

Publications and source records attributed to B Shapiro.

At least 37 records · Page 2Linked to original sources

Scintigraphy of acute inflammatory lesions in rats with radiolabelled recombinant human interleukin-8.

We compared 125I-labelled recombinant human interleukin-8 (125I-IL-8) with 111In-labelled human leukocytes (111In-WBC) and 67Ga-citrate for scintigraphic depiction of acute sterile inflammatory lesions in rats. Radioiodination of IL-8 was catalysed by chloramine-T, and human leukocytes were radiolabelled with 111In-oxine. Inflammatory lesions were induced in male rats by subcutaneous injection of 2% carrageenan suspension into their left hindlimbs. Twenty-four hours later, each rat received 1.8-3.7 MBq (50-100 microCi) of a single agent by intravenous injection. Sequential whole-body scintigrams were obtained between 0 and 96 h post-injection. Activities in the lesion-bearing and control hindlimbs were expressed as regional percent injected activity corrected for physical decay (%IA) by reference to concurrently imaged standards, and for 125I-IL-8 by direct tissue counting at necropsy as well. 125I-IL-8 displayed appropriate electrophoretic mobility, retained chemotactic and high-affinity receptor-binding activity in vitro, and exhibited exponentially decreasing activity in most tissues beginning shortly after intravenous injection. Scintigrams showed asymmetrically increased activity in the lesion-bearing hindlimb for all three agents. By scintigraphy, 125I-IL-8 activity in the lesion-bearing hindlimb reached a zenith 1-3 h post-injection at 4.8 +/- 0.5 %IA and decreased exponentially thereafter, with little change in lesioned-to-control limb ratios (mean L/C = 3.0 +/- 0.7) over the imaging period. By direct tissue counting, abscess-associated mean IL-8 activity per gram of tissue increased to four times that of adjacent muscle and nearly seven times that of contralateral muscle by 24 h post-injection. Lesion-bearing hindlimb 111In-WBC activity also rose rapidly, reaching 4.2 +/- 0.6 %IA by scintigraphy at 3 h and an eventual plateau (maximum of 4.5 +/- 0.4 %IA) by 24 h. 67Ga scintigraphic activity in the lesion-bearing hindlimb peaked briefly at 3-6 h post-injection (9.2 +/- 0.5 %IA) and subsequently declined to a constant level of about 7.5 %IA. However, L/C for 111In-WBC and for 67Ga-citrate each averaged only 1.5 +/- 0.3 over the imaging period, compared with a mean L/C of 1.2 +/- 0.2 for a blood pool radiotracer. We conclude that 125I-IL-8 is rapidly and selectively concentrated in regions of acute inflammation, presumably by high-affinity binding to IL-8 receptors on neutrophils within the inflammatory focus. Radioiodinated IL-8 offers an attractive alternative to 67Ga-citrate and 111In-WBC for early imaging of acute inflammatory lesions, and demonstrates significantly higher target-to-nontarget activity ratios in this model. The potential usefulness of radiolabelled IL-8 for clinical scintigraphy should be evaluated.

Animals

Intrapericardial paragangliomas (pheochromocytomas): imaging features.

OBJECTIVE: The imaging features of intrapericardial paragangliomas (pheochromocytomas) are described. MATERIALS AND METHODS: We conducted a retrospective study of the imaging features of all intrapericardial paragangliomas seen at our institution over the last 13 years. RESULTS: In this study, intrapericardial paragangliomas were typically located adjacent to or involved the left atrium. The diameter of the tumors ranged from 3 to 8 cm. Metaiodobenzylguanidine (MIBG) scintigraphy revealed 11 of 12 tumors (sensitivity = 92%). After MIBG scintigraphic location, dynamic contrast-enhanced CT revealed all 12 tumors. CONCLUSION: Intrapericardial paragangliomas are rare tumors, typically located adjacent to or involving the left atrium. For initial detection, regional location of these extraadrenal tumors, and detection of distant metastases, MIBG scintigraphy is recommended. Dynamic contrast-enhanced CT or MR imaging can then provide detailed anatomic delineation before surgical resection.

3-Iodobenzylguanidine

Malignant paraganglioma of the prostate: case report, depiction by meta-iodobenzylguanidine scintigraphy and review of the literature.

OBJECTIVE: To describe the 123-I-MIBG scintigraphic, CT, MRI, operative and pathological findings in a case of malignant prostatic paraganglioma and to review the literature on this very rare tumor. EXPERIMENTAL DESIGN: Clinical imaging and pathological correlation of data in a referred patient. SETTING: Regional referral center and tertiary referral academic medical center. PATIENT: 17 year old man presenting with painless hematuria and a large prostatic mass. Interventions and measures. Renal ultrasound, transrectal ultrasound, ultrasound guided prostatic biopsy, pelvic CT and MRI, planar and SPECT 123-I-MIBG scintigraphy, and surgical exploration. RESULTS: The patient had a significant hydronephrosis of the left kidney and marked enlargement (120 ml) of the prostate gland by ultrasound. Ultrasound guided biopsies of the prostate and a left pelvic lymph node revealed a neuroendocrine tumor staining positive for chromogranin. CT and MRI revealed a large tumor of the prostate invading the seminal vesicles, bladder and rectum with extensive pelvic lymph node spread. The primary tumor and one of the nodes were shown to be 123-I-MIBG avid confirming the neuroendocrine nature of the tumor. The lesion was unresponsive to chemotherapy and unresectable at surgical exploration. CONCLUSIONS: To date there have only been 5 reports of prostatic paragangliomas. To our knowledge this is the first to have been studied by MIBG scintigraphy and like most paragangliomas it was MIBG-avid.

3-Iodobenzylguanidine

Specificity of radioiodinated MIBG for neural crest tumors in childhood.

UNLABELLED: The high sensitivity of metaiodobenzylguanidine (MIBG) scintigraphy for sympathomedullary tumors such as neuroblastoma and pheochromocytoma is well documented. The specificity of MIBG scintigraphy for these tumors is also high but has been incompletely characterized for other neural crest tumors and non-neural crest tumors of childhood. METHODS: The medical records and MIBG scans of all children who had undergone MIBG scintigraphy for known or suspected neuroblastoma or pheochromocytoma were retrospectively reviewed at five major referral centers. Those patients found to have pathologies other than neuroblastoma or pheochromocytoma form the basis of this study. RESULTS: One hundred children with a total of 110 lesions met the inclusion criteria. All had negative MIBG scans except 1 of 2 children with infantile myofibromatosis, 1 of 2 with neuroendocrine carcinomas, 1 of 2 with pancreaticoblastomas and 1 of 10 with primitive neuroectodermal tumors. CONCLUSION: MIBG scintigraphy is highly specific for neuroblastoma and pheochromocytoma. Only 4% (4/100) of nonsympathomedullary tumors (non-pheochromocytoma and non-neuroblastoma) in childhood showed MIBG uptake, of which only 2% (2/100) were of non-neural crest origin.

3-Iodobenzylguanidine

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

Elevated parathyroid hormone-related peptide associated with lactation and bone density loss.

OBJECTIVE: To investigate the hypothesis that parathyroid hormone-related peptide (PRHrP) may be involved with bone loss and recovery as a means of providing adequate calcium and phosphate to infants. DESIGN: An 18-month prospective cohort study. SETTING: General community setting with recruitment occurring at birthing education classes. PARTICIPANTS: Volunteer sample of 115 postpartum healthy women aged 20 to 40 years, and 0 or 1 parity prior to parturition with no intent to breast-feed or intent to breast-feed at least 6 months. MAIN OUTCOME MEASURES: Parathyroid hormone-related peptide, prolactin, estradiol, 1,25-dihydroxyvitamin D, 24-hydroxyvitamin D, femoral bone mineral density, and bone turnover markers were measured in 115 postpartum women at 2 weeks, 2 months, 4 months, 6 months, 12 months, and 18 months postpartum. Lumbar bone mineral density was measured at 2 weeks, 6 months, 12 months, and 18 months postpartum. RESULTS: Elevated PTHrP values were significantly associated (P<.001) with breast-feeding status, elevated prolactin levels, and lower serum estradiol levels, conditions occurring during lactation. Furthermore, elevated PTHrP levels were negatively and significantly associated (P<.01) over time with bone mineral density change at both the spine and the femoral neck, even after accounting for prolactin levels, breast-feeding status, return of menstruation, estradiol levels, PTH levels, 1,25-dihydroxyvitamin D levels, dietary calcium intake, physical activity, and body size. CONCLUSION: These data clearly support the hypothesis that PTHrP is an alternative mechanism associated with bone loss and recovery during and subsequent to lactation.

Absorptiometry, Photon

Successful and unsuccessful approaches to imaging carcinoids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue.

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dL-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumour-to-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors experience of 131I- and 123I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131I-MIBG. Three of the seven patients with known metastatic disease had positive 131I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123I-MIBG there were four true-negative scans and one false-negative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 pentetreotide . Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111In-pentetreotide. The experience with 123I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131I-MIBG and 111In-pentetreotide relative to 131I-PIPA may be related to the fact that 131I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111In-pentetreotide binds to cell surface receptors, whereas 131I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.

3-Iodobenzylguanidine

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

Three-phase skeletal scintigraphy in gouty arthritis: an example of potential diagnostic pitfalls in radiopharmaceutical imaging of the extremities for infection.

The three-phase bone scan has been shown to be useful in the diagnosis of osteomyelitis, with a high sensitivity and specificity under optimal conditions. However, there are many causes of focally-increased uptake of Tc-99m diphosphonates in the extremities that may mimic infection, especially when there is increase on all three phases. Radiolabeled leukocyte scintigraphy is often performed in this clinical setting, although many pitfalls resulting in false-positive scans still remain. The authors present three cases of gouty arthritis in which skeletal scintigraphy illustrates this lack of specificity. Further causes of increased extremity uptake are reviewed, with attention to those that have been reported to show an increase on all three phases of the bone scan. Additional factors that can improve the specificity of the bone scan are discussed, as are the panoply of more recent scintigraphic approaches aimed at distinguishing infection from aseptic inflammation in the extremity. Unfortunately, no nuclear medicine procedure to date has proven itself to be reliably specific for infection.

Aged

I-131 localization in acute megakaryocytic leukemia.

A case of acute megakaryocytic leukemia in a 13-month-old infant was encountered in whom an abnormal bone scan was associated with abnormal I-131 MIBG uptake in the femoral bone marrow. The normal platelet will take up MIBG and thus, uptake of this radiopharmeceutical by the malignant megakaryocyte, a platelet precursor, may be caused by the same mechanism.

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

Disseminated bone marrow metastases of insular thyroid carcinoma detected by radioiodine whole-body scintigraphy.

We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing diffuse abnormal uptake throughout the skeleton. The scintigraphy closely resembled the pattern of [131I]MIBG distribution in children with bone marrow metastases of neuroblastoma. The extent of involvement was underestimated by bone scintigraphy and radiography. Insular carcinoma of the thyroid in the bone marrow was subsequently demonstrated by biopsy. The patient was treated with 242 mCi 131I given in two courses, which led to severe myelosuppression and died as a result of progressive disease and severe pancytopenia 10 mo after initial therapy.

Biopsy

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