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Biomedical subjects

R Mastrangelo

Publications and source records attributed to R Mastrangelo.

At least 37 records · Page 2Linked to original sources
PubMed1994

Nuclear medicine imaging in pediatric oncology.

Nuclear medicine imaging techniques, whether applied in the initial diagnosis or in assessing the response to therapy, are indispensable in the evaluation of malignant diseases that afflict infants and children. The major role of these techniques (bone, 67Ga and 201Tl scintigraphy, imaging with labeled leucocytes, immunoscintigraphy) is that of complementing, in an essential manner, other first choice diagnostic investigations (radiological, bioptic, etc.) such as in evaluating malignant skeletal tumors, soft tissue sarcomas, lymphomas, leukemia and histiocytosis X. Nevertheless, due to their high tissue specificity and/or diagnostic reliability, 99mTc-MDP (or analogues) imaging in the screening of bone metastases, 123/131I-MIBG scintigraphy in the diagnosis and management of neuroblastoma and 131I whole body scan in staging postoperatively differentiated thyroid cancers are proposed as first choice modalities. Well established (131I therapy) or recently developed (131I-MIBG therapy and radioimmunotherapy) therapeutic modalities are available today to be either integrated with or to substitute the conventional treatment of differentiated thyroid carcinoma and neuroblastoma.

3-Iodobenzylguanidine↗
PubMed1993

Uptake and storage of m-iodobenzylguanidine are frequent neuronal functions of human neuroblastoma cell lines.

The mechanisms of the uptake and release of m-iodobenzylguanidine (MIGB) have been studied in 5 neuroblastoma (NB) cell lines and in 4 clonal NB sublines with a homogeneous phenotype. A specific uptake system for MIBG was found in 8 of 9 NB cell lines or subpopulations. The uptake was characterized by temperature dependency, high affinity, saturability, sodium dependency, and imipramine sensitivity. The majority of NB cell lines that possessed a specific uptake system for MIBG were also able to efficiently store the incorporated drug. However, 3 NB cell lines were identified without the ability to retain high levels of MIBG, despite the presence of a specific uptake system. We also report that a clonal subline, SH-EP1, which has a nonneuroblastic phenotype, failed both MIBG uptake and retention. Conversely, the parental cell line, SK-N-SH, and the neuroblastic subline SH-SY5Y possessed both a specific uptake system and the ability to store MIBG. In addition, the induction of neuronal differentiation with retinoic acid increased the velocity of uptake and the storage efficiency for MIBG in the clonal subline SH-SY5Y. We conclude that MIBG uptake and storage should be considered to be frequent but independent neuronal functions of human NB cells.

3-Iodobenzylguanidine↗
PubMed1993

Critical observations on neuroblastoma treatment with 131-I-metaiodobenzylguanidine at diagnosis.

Results of treatment with 131-I-Metaiodobenzylguanidine (131-I-MIBG) in patients with resistant neuroblastoma appear encouraging if one considers that most of the patients had far advanced, intensively pre-treated disease. To further explore the potential role of this new drug in untreated patients, we treated 3 children with stage III neuroblastoma. All three of our cases received 131-I-MIBG at relatively low dose with the complete disappearance of the tumor mass in case 1, whereas in cases 2 and 3 CT scan showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131-I-MIBG uptake of a tracer dose in the remaining tumor. Particularly, in case 2, the persistence and subsequent progression of part of the tumor mass without 131-I-MIBG uptake after a therapeutic dose of 131-I-MIBG, which apparently destroyed the 131-I-MIBG-positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131-I-MIBG uptake and the other without. Besides the biological implications of the 131-I-MIBG uptake heterogeneity in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131-I-MIBG administered at diagnosis is sufficient to destroy either the primary tumor completely (case 1) or the part of the tumor (case 2 and 3) which shows 131-I-MIBG uptake, without any significant hematologic toxicity. Furthermore, a single course of 131-I-MIBG at the dosage employed does not appear to jeopardize the subsequent use of chemotherapy. In conclusion, if our data are confirmed by further investigation, 131-I-MIBG may be included as a front line drug shortly followed by chemotherapy in future treatment strategies of advanced neuroblastoma without or with minimal bone marrow infiltration.

3-Iodobenzylguanidine↗
PubMed1992

Cerebrospinal fluid pharmacokinetics of carboplatin in children with brain tumors.

The pharmacokinetics of carboplatin in cerebrospinal fluid (CSF) and plasma was studied in five children with brain tumors (four medulloblastomas and one ependimoblastoma) who underwent preirradiation treatment with carboplatin. Carboplatin pharmacokinetics was studied following the administration of 600 mg/m2 as a 1-h infusion. Four children were treated a few weeks after surgery, whereas one child with an unresectable tumor was treated prior to surgery. All patients had a ventricular-peritoneal CSF shunt connected to a subcutaneous reservoir. Total platinum and free carboplatin were measured. The mean AUC values for free carboplatin in CSF and plasma were 2.29 +/- 1.20 and 8.18 +/- 1.27 mg ml-1 min, respectively. The mean ratio of CSF AUC to plasma AUC was 0.28 (range, 0.17-0.46). Both plasma peak levels and AUC values showed limited interpatient variability. On the other hand, carboplatin levels in CSF showed substantial interpatient variability, with a greater than 5-fold difference in peak levels and a 3-fold difference in AUC values being recorded. The interpatient difference in CSF pharmacokinetics may have been related at least in part to the different anatomical alterations induced by the surgical procedures or by the presence of a large tumor mass. In the four evaluable patients exhibiting macroscopic residual tumor, we observed one complete remission (CR) and two partial remissions (PR) following two cycles that consisted of two doses of 600 mg/m2 carboplatin given on 2 consecutive days (total dose, 1200 mg/m2) and were separated by a 1-month interval. These results may give some indication as to the optimal dose and schedule for carboplatin administration in the treatment of primitive neuroectodermic tumors (PNET).

Brain Neoplasms↗
PubMed1991

Cranial irradiation and cerebrospinal fluid levels of 6-mercaptopurine in children with acute leukemia.

We measured 6-mercaptopurine levels in the cerebrospinal fluid and plasma of 15 children undergoing treatment for acute leukemia. Plasma and cerebrospinal fluid samples obtained by lumbar puncture were collected before, during, and after cranial irradiation in order to evaluate a possible change in blood-brain barrier permeability to orally administered 6-mercaptopurine. Considerable interpatient variability has been observed in both plasma and cerebrospinal fluid 6-mercaptopurine levels. No statistical differences in the 6-mercaptopurine cerebrospinal fluid levels under the three different conditions could be detected. Our data suggest that cranial irradiation does not significantly influence the cerebrospinal fluid levels.

Administration, Oral↗
PubMed1990

The diagnostic and therapeutic utility of radioiodinated metaiodobenzylguanidine (MIBG). 5 years of experience.

The authors' experience of more than 5 years in the diagnostic and therapeutic use of radioiodinated MIBG in neural crest tumors is reported. 123I/131I-MIBG scintigraphy was performed in 158 patients: 75 suspected (24 proven) pheochromocytomas (pheos), 43 neuroblastomas (NB), 20 medullary thyroid carcinomas (MTC), 6 ganglioneuromas, 5 carcinoids and 1 insulinoma. Eight cases of tumors not originating from the neural crest were also investigated. The diagnostic sensitivity of the method was above 90% both in pheos and NB (primary tumors and bone metastases). The examination was less effective in localizing MTC (sensitivity = 64.4% in primary or residual/recurrent tumors). The scintigraphic outcome was negative in ganglioneuromas, carcinoids and insulinoma. Specificity was very high (greater than 95%), and no false positive results were found in tumors not deriving from the neural crest. 131I-MIBG treatment was administered to four patients with malignant pheo, nine with NB and four with MTC. Therapy resulted in a complete response in one pheo, two NB and one MTC treated after surgery or at diagnosis (one NB); it gave partial response and prolonged remission in five advanced cases (one pheo, two NB and two MTC); it resulted in temporary stabilization of the disease in one pheo and two NBs; it was ineffective in four cases.

3-Iodobenzylguanidine↗
PubMed1989

131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis.

Radioactive metaiodobenzylguanidine (131I-MIBG) is taken up specifically by neuroblastoma cells and appears to represent a new treatment modality in patients with advanced neuroblastoma. Taking into account the fact that all patients so far treated were heavily pretreated and resistant to chemotherapy, the results obtained appear encouraging. In order to explore further the potential role of this new drug in untreated patients, we treated with 131I-MIBG a child with stage III neuroblastoma at diagnosis. We observed the complete disappearance of a large abdominal tumor mass after a relatively low dosage of 131I-MIBG, with minimal hematologic toxicity. No further treatment was given and, at present, the patient is alive with no evidence of disease 18 months from diagnosis. This child represents, to our knowledge, the only case of neuroblastoma thus far treated at diagnosis and the excellent response obtained suggests the need for further investigations of this therapy in untreated patients.

3-Iodobenzylguanidine↗
PubMed1987

Treatment of neuroblastoma with 131I-metaiodobenzylguanidine.

Seven patients with neuroblastoma (six children and one adult) were treated with therapeutic doses of high specific activity 131I-metaiodobenzylguanidine (131I-MIBG). Six patients were in stage IV and unresponsive to conventional treatment. One patient, in stage III, was treated at diagnosis, an approach never previously reported. Single doses of 131I-MIBG varying from 70 to 184 mCi split into two parts were administered by slow i.v. infusion (4 to 8 hours) at 2- to 4-day intervals. The following results were obtained in the six evaluable patients: two patients showed transient stabilization of the disease; three had an objective response, with shrinking of the primary tumor and/or regression of the metastatic lesions. Of these three patients, two suffered relapses at 2 and 7 months, respectively, from the first course of MIBG. The third patient, in whom the residual disease almost completely disappeared following MIBG therapy, is still alive in complete remission after autologous bone marrow transplantation with a follow-up of 14 months. The single patient treated at diagnosis showed a dramatic response to a relatively low dosage of MIBG, with histologically proved disappearance of the tumor mass. Our data indicate that MIBG may be useful in the treatment of neuroblastoma unresponsive to conventional chemotherapy. The complete response observed in the patient treated at diagnosis suggests that the full potentiality of MIBG therapy should be explored in untreated patients.

3-Iodobenzylguanidine↗
PubMed1986

Prognostic relevance of clinical pharmacology of antileukemic drugs.

Response to treatment is the most important prognostic factor in children undergoing treatment for acute lymphoblastic leukemia. Factors that interfere with the pharmacokinetic determinants of anti-leukemic compounds may cause a decreased activity of one or more of the drugs included in the treatment protocol. Noncompliance with the prescribed treatment, individual pharmacokinetic differences, interference with oral drug absorption, and different guidelines for dose reduction related to toxicity are some of the factors responsible for a decreased or variable antileukemic activity which may influence treatment results.

Antineoplastic Agents↗
PubMed1986

Influence of food intake on bioavailability of oral 6-mercaptopurine in children with acute lymphoblastic leukemia.

Plasma levels of 6-mercaptopurine (6-MP) were measured after oral administration in 17 children with acute lymphoblastic leukemia (ALL). In the fasting state or after a breakfast consisting of 250 ml milk and 50 g biscuits, 6-MP was administered at a dose of 75 mg/m2. In patients studied in a fasting state, the mean time to plasma peak (tmax) level was 1.2 h, whereas in patient studied after breakfast the mean tmax was 2.3 h. This difference is statistically significant (p less than 0.001). Moreover, the 6-MP peak plasma concentration (cmax) and the areas under the plasma concentration time curves (AUC) were significantly reduced when the drug was administered after breakfast. The mean Cmax +/- SD were 0.98 +/- 0.54 microM and 0.63 +/- 0.48 microM, respectively (p less than 0.05). The mean 6-MP AUC +/- SD in patients studied in a fasting state and after breakfast were 143 +/- 69 microM min and 105 +/- 68 microM, respectively (p less than 0.01). These results indicated that 6-MP should be taken in a fasting state to optimize drug absorption in children undergoing chemotherapy for ALL.

Administration, Oral↗
PubMed1981

Release of glycosyltransferase and glycosidase activities from normal and transformed cell lines.

The release of galactosyltransferase, sialyltransferase, and several glycosidase activities into the growth media from several normal and transformed cell lines was examined. Six of the seven cell lines released galactosyltransferase into their culture media. Only the human leukemia CCRF-CEM cells failed to release demonstrable galactosyltransferase activity. Release of galactosyltransferase activity into the media closely paralleled the growth curves for all but the BHKpy cells. These cells continued to release peak levels of galactosyltransferase activity into the culture media after their growth had plateaued. Media galactosyltransferase activity was unaffected by Triton X-100 treatment had remained in the supernatant fraction of a 100,000 X g, 12-hr centrifugation, suggesting that the cells release galactosyltransferase in a soluble form. In contrast to galactosyltransferase activity, only one of the cell lines (L1210) released sialyltransferase activity in appreciable amounts. Even this level of activity was 20-fold less than that observed for galactosyltransferase in the media from L1210 cells. Of the nine glycosidase activities assayed, only N-acetylglucosaminidase was observed in significant amounts in the media from all but the CCRF-CEM cells. However, N-acetylglucosaminidase release did not correlate closely with cell growth. These findings suggest a relatively specific release of galactosyltransferase and N-acetylglucosaminidase activities by cells in tissue culture. Moreover, the release of galactosyltransferase closely parallels cell growth. The significance of these released enzymes, especially to cell growth, has yet to be determined.

Acetylglucosaminidase↗