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Biomedical subjects

L Maffioli

Publications and source records attributed to L Maffioli.

At least 37 records · Page 2Linked to original sources
PubMed1993

Salvage treatment after r-interferon alpha-2a in advanced neuroendocrine tumors.

The use of inteferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN alpha-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIGB uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m2 intravenously days 1, 2, 3 and epirubicin 75 mg/m2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective.

3-Iodobenzylguanidine↗
PubMed1992

CA 15.3 determination in patients with breast cancer: clinical utility for the detection of distant metastases.

In 81 healthy women, 26 pregnant women, 25 patients with fibrocystic disease and 144 breast cancer patients, the overall diagnostic sensitivity and specificity of the CA 15.3 test was 27 and 97%, respectively. The positive and negative predictive values were 93 and 43%. In 150 node-negative patients taking part in a chemoprevention trial CA 15.3 was assayed at baseline and every 4 months for a median follow-up of 24 months (range 4-48). In these patients, 5 had local recurrences, 1 had a regional recurrence, 9 had distant metastases and 3 developed cancer in the contralateral breast. Among the patients with recurrences, those with distant metastases showed the highest ratio of CA 15.3 increase (8/9); in local and regional recurrences, this ratio was lower (2/6). The patients with contralateral breast cancer had no significant increase in CA 15.3. Patients in whom metastases were detected showed an increase in CA 15.3 4-48 months before clinical or instrumental detection of the metastases.

Adult↗
PubMed1992

99Tcm-MIBI single photon emission tomography (SPET) for detecting myocardial ischaemia and necrosis in patients with significant coronary artery disease.

The ability of 99Tcm-methoxyisobutylisonitrile (MIBI) single photon emission tomography (SPET) to detect myocardial ischaemia and necrosis was assessed in 56 patients (45 male, 11 female, aged 55 +/- 5 years), with clinically recognized ischaemic heart disease (IHD). All underwent coronary angiography (CA) and left ventriculography (LV). SPET images were obtained at rest and at peak exercise (Modified Bruce) 90 min after injection of 99Tcm-MIBI (650-850 MBq). Data were acquired in 30 min over 180 degrees (from 45 degrees RAO to 45 degrees LPO) with no correction for attenuation, using a 64 x 64 matrix. The presence of persistent (P) or reversible (R) perfusion defects (PD) was then correlated to the resting and exercise ECG and to the results of CA and LV. Of the 56 patients, 34 had reversible underperfusion (RPD), 46 persistent underperfusion (PPD) and 31 had both. The occurrence of RPD correlated well with the occurrence of exercise-induced ST segment depression and/or angina (27 patients of 34 patients, 79%) and with the presence of significant coronary artery disease (CAD) (33 of 44, 73%). In 45 of 46 patients (98%) PPD corresponded to akinetic or severely hypokinetic segments (LV) usually explored by ECG leads exhibiting diagnostic Q waves (42 of 46 patients, 91%). The scan was normal both at rest and after stress in four of 11 patients with no CAD, and in two of 45 patients with CAD. Finally, an abnormal resting scan was seen in seven of 11 patients with normal coronary arteries, of whom six had regional wall motion abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Biodistribution of Tc-99m methoxy-isobutyl-isonitrile (MIBI) in humans.

Hexakis (methoxyisobutilisonitrile) technetium(I), 99mTc-MIBI, has been proposed for myocardial perfusion studies. We have evaluated the biodistribution of this new agent in normal volunteers at rest and after stress. The biodistribution of 99mTc-MIBI is characterized by rapid blood clearance and a consequently early myocardial uptake. The initial intense hepatic activity is cleared into the gallbladder at 1 h after injection, and the best target to non target ratio is observed at 60-90 min after injection. Absorbed radiation dose calculations show that the thyroid is the critical target organ (230 mRad/mCi at rest), presumably because of 99mTc-pertechnetate generated in vivo. Our results indicate that 99mTc-MIBI is a promising tracer for myocardial perfusion imaging.

Adult↗
PubMed1989

Cationic complexes of technetium for myocardial imaging.

Over the past 15 years a major goal of research in cardiovascular nuclear medicine has been the development of 99mTc complexes that could replace 201Tl and thus enhance the utility of myocardial perfusion imaging. This paper presents an overview of the current state-of-art of the development of cationic 99mTc complexes for this purpose. Cationic 99mTc complexes that have been evaluated as myocardial perfusion imaging agents in human volunteers and/or animals are discussed and classified on the basis of the oxidation state of the technetium center.

Animals↗
PubMedDate not supplied

Uptake of tritiated thymidine, deoxyglucose and methionine in three lung cancer cell lines: deoxyglucose uptake mirrors tritiated thymidine uptake.

[(18)F]-fluorodeoxyglucose and [(11)C]-methionine are tracers which are widely used in oncological positron emission tomography. This study has been designed to assess the deoxyglucose and methionine uptake behaviour in three cell lines from different lung cancer histotypes. Tracer uptake was compared with proliferative activity as determined by growth curves and tritiated thymidine uptake. Deoxyglucose paralleled thymidine in all cell lines, peaking in the lag phase, decreasing throughout the exponential phase, and reaching its minimum in the plateau phase. The correlation was statistically verified and Spearman's rho ranged from 0.79 to 0.99. The absolute methionine uptake was always highest and always peaked on day 2, followed by a quite rapid decrease. However, besides the delay in maximum uptake, methionine incorporation was also related to proliferation, although the statistical correlations were weaker. These results show for the first time a clear correlation between deoxyglucose uptake and cell proliferation in a model comparing tracer uptake in different growth phases. Although delayed, methionine uptake was also related to cell growth and its greater intensity could be of interest for clinical use.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

State of the art of sentinel node biopsy in oncology.

Sentinel node biopsy has become a standard diagnostic procedure to assess lymph node status of various tumors. The combination of blue dye and a radioactive tracer offers the best chances of identifying the sentinel lymph node. Most progress in the technique of the sentinel node procedure has been made in melanoma and breast cancer. In melanoma, sentinel node biopsy has been introduced as a fundamental procedure for staging. Information on the lymphatic drainage from a melanoma can have a direct impact on the surgery. More recently, the technique has been successfully introduced in the management of breast cancer, in which a large number of unnecessary axillary dissections could be avoided. However, there are many other potential fields of application of the sentinel node biopsy (e.g. endometrial, vulvar, head and neck cancers) that are worthy of investigation. In any case, multicenter trials are required to standardize the procedures, taking into account several variables such as particle size and mode of delivery of the radiotracer, amount of radioactivity administered, number and location of injections, and choice of the hand-held probe. We briefly describe the technical and historical aspects of the sentinel node biopsy and summarize the main clinical trials proposed and/or performed in the field.

Biopsy↗
PubMedDate not supplied

Sentinel node biopsy in patients with cutaneous melanoma of the head and neck.

Biopsy of head and neck sentinel nodes (SNs) can be technically problematic due to the unpredictable and variable drainage patterns of this anatomic region. The aim of the present study was to evaluate the feasibility of SN biopsy for cutaneous melanoma of the head and neck. We performed SN biopsy in 17 patients affected by stage I cutaneous melanoma of the head and neck on the basis of lymphoscintigraphy, blue dye and gamma probe. A total of 24 procedures were performed. Drainage to more than one lymphatic basin was observed in five patients (two basins in three cases and three basins in two cases) and in all cases SN biopsy was performed in all basins. The biopsy distribution by site was: six cervical nodes, five parotid nodes, four supraclavicular and submandibular nodes, three auricular and axillary nodes. The SN identification rate was 87.5% (21/24); metastases were discovered in four cases, with a positivity rate of 23.6%. At the time of writing, 1 patient is alive with local disease, 3 patients are dead and 13 are alive and free of disease with a follow-up ranging from 1 to 40 months (median, 21 months) following SN biopsy. In our opinion preoperative lymphoscintigraphy and the intraoperative use of a gamma probe are useful for the identification of lymphatic drainage of cutaneous melanoma of the head and neck.

Coloring Agents↗
PubMedDate not supplied

Indium-111-DTPA-octreotide scintigraphy modulation by treatment with unlabelled somatostatin analogue in small-cell lung cancer.

AIMS AND BACKGROUND: Small-cell lung cancer (SCLC) tissue expresses somatostatin receptors and can be visualized by means of the indium-111-labelled somatostatin analogue DTPA-D-Pheoctreotide. The aim of the study was to investigate whether treatment with a cold somatostatin analogue can affect the imaging of somatostatin receptor scintigraphy. METHODS: Three patients with SCLC were treated with 200 micrograms of cold octreotide three times a day subcutaneously for 7 days. Whole body and planar scintigraphy was performed before and after the treatment. RESULTS: 111In-DTPA-octreotide uptake was increased in cancer lesions, whereas fixation in normal tissues (liver, spleen, kidneys) decreased. CONCLUSIONS: This is the first demonstration of an enhancement of SCLC imaging following unlabelled somatostatin analogue administration. Similar results have been described by other authors in a limited number of carcinoid tumors.

Carcinoma, Small Cell↗
PubMedDate not supplied

Clinical utility of radioimmunoscintigraphy of non-Hodgkin's lymphoma with radiolabelled LL2 monoclonal antibody, LymphoSCAN: preliminary results.

AIMS AND BACKGROUND: Adequate clinical staging of non-Hodgkin's lymphoma patients is essential because only localized disease can be treated satisfactorily. Many imaging procedures are necessary to stage the disease accurately. The objective of this study was to evaluate the efficacy of an antilymphoma antibody in the Fab' fragment form, labelled with 99mTc, to detect malignant lesions. METHODS: Radioimmunodetection (RAID) with 99mTc-labelled B-cell lymphoma monoclonal antibody IMMU-LL2-Fab' (LymphoSCAN; Immunomedics, Morris Plain, NJ, USA) was investigated in 10 patients (5 females and 5 males; age range, 20-72 years) with histologically proved non-Hodgkin's lymphoma. Of the 10 lymphomas, 7 were intermediate grade and 3 were low grade. Whole body images with multiple planar views were obtained at 30 min, 4-6 and 24 h after i.v. injection of 1 mg LL2-Fab' labelled with 740-925 MBq of 99mTc. SPET of the chest or abdomen was performed in all patients 5-8 h after the immunoreagent injection. RESULTS: No adverse reactions were observed in any patient after Mab infusion, and no appreciable changes were seen in the blood counts, renal or liver function tests. A total of 18 of 21 (85.7%) lymphoma lesions were detected by RAID. All the tumor localizations were confirmed by clinical examination and with other imaging techniques, such as CT scan, MRI or gallium scan. In this series of patients no false-positive results were noted. As regards the biodistribution of the immunoreagent, no appreciable bone marrow activity was seen; splenic targeting was demonstrated in all patients; the tumor-to-non-tumor ratios ranged from 1.2 to 2.8 ad measured by the ROI technique; no difference in uptake was noted for different tumor grades. The images obtained 24 h after injection did not reveal new lesions, but areas of doubtful uptake were seen as positive focal areas in the delayed scan. CONCLUSIONS: LymphoSCAN seems to be useful for detection, staging and follow-up of non-Hodgkin's lymphoma patients.

Adult↗
PubMedDate not supplied

Applications of 99mTc-sestamibi in oncology.

Hexakis (2-methoxyisobutylisonitrile) technetium-99m (99mTc-SestaMIBI) is a radiopharmaceutical used in nuclear medicine for myocardial perfusion imaging. In the literature different non-cardiac applications of 99mTc-SestaMIBI have been reported. Clinical studies have been performed also in non-oncologic disease (such as thyroid adenoma, diabetic foot, osteomyelitis, pulmonary actinomycosis, aneurysmal bone cyst. Sudeck's atrophy). Several models for the uptake mechanism of this radiopharmaceutical have been proposed such as binding to an 8-10 kDa cytosolic protein, simple lipid partitioning, or a membrane translocation mechanism involving diffusion and passive transmembrane distribution. Most evidence points in the direction of the third hypothesis. Many studies have indicated that uptake of hexakis (alkylisonitrile) technetium complexes is dependent on mitochondrial and plasma membrane potentials like other lipophilic cations. This explains the initial biodistribution of 99mTc-SestaMIBI to tissues with negative plasma membrane potentials and with relatively high mitochondrial content (like heart, liver, kidney and skeletal muscle tissue). Malignant tumours also possess these properties in order to maintain their increased metabolism. This behaviour encouraged the study of 99mTc-SestaMIBI as an interesting tracer imaging various tumour types: osteosarcoma, brain, lung, breast, nasopharyngeal, parathyroid and thyroid cancer. Recent research on cell cellular physiology has further revealed an active transport of 99mTc-SestaMIBI out of the tumour cells, against the potential gradient. The same mechanism is also responsible for resistance to a structurally and functionally different group of cytotoxic agents such as vinca alkaloids, epipodophyllotoxins, anthracyclins and actinomycin D. This peculiar type of resistance is due to amplification of the mammalian MDR1 gene, located on chromosome 7. For this reason the 99mTc-SestaMIBI uptake in vivo could permit the prediction of the response to the chemotherapy, when the decreased accumulation of 99mTc-SestaMIBI implies the presence of P-gp enriched tissues. In the next future a particular attention should be dedicated to this matter since one of the most important goals of the clinical trials is the demonstration of the usefulness of 99mTc-SestaMIBI for in vivo assessment of multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Gallium-67 as a tumor-seeking agent in lymphomas--a review.

BACKGROUND: At present 67Ga can be considered one of the most widely used viability radiotracers. There is general consensus in the literature that 67Ga has the highest clinical value in the management of lymphoma patients. METHODS: We critically discuss the role of gallium scintigraphy in lymphoma patients on the basis of the experience of the Nuclear Medicine Division at the National Cancer Institute of Milan. RESULTS AND CONCLUSIONS: The sensitivity of gallium scan is very high (80-90%) in the staging and follow-up of Hodgkin's disease, and the method is also of great importance in the follow-up of lymphoma patients. We recommend scintigraphy to study the residual mediastinal mass after treatment. Our experiences during the follow-up of 189 lymphoma patients clearly showed the superior performance of gallium scan compared to MRI in the study of the mediastinal region after treatment. Sensitivity and specificity were both very high (90% and 96.9% vs 88.7% and 89.2%, respectively). Gallium scintigraphy can also be used to study the disease-free interval, post-treatment survival, early signs of recurrence and treatment response times. Comparison of the survival curves of 33 patients with diffuse large cell Non-Hodgkin's lymphoma examined at the National Cancer Institute showed a statistically significant difference (logrank test, P = 0.0125) between patients with positive and those with negative gallium scan after 4-6 cycles of chemotherapy.

Animals↗
PubMedDate not supplied

Pilot, multicenter and prospective trials with an anti-CEA antibody.

In this paper we summarize the investigations performed by our group utilizing an anti-CEA monoclonal antibody (F023C5) labelled with different radionuclides in humans. Since 1983 radioimmunoscintigraphy (RIS) was performed on 51 patients with 64 localizations of colo-rectal carcinoma (pilot study). A multicenter clinical trial in a large number of patients (509 pts of which 284 with gastrointestinal cancer) was subsequently carried out in collaboration with ten nuclear medicine centres. High sensitivity and specificity values were obtained by these studies and many unsuspected lesions were recorded. In order to better define the clinical role of RIS, a prospective study was performed on 59 patients with suspected local relapses of colo-rectal cancer. A comparative evaluation of RIS, CT scan, US and MRI was done. RIS and MRI had the highest accuracy (86%) followed by CT scan (68%) and US (54%).

Carcinoembryonic Antigen↗
PubMedDate not supplied

Enhancement of in vivo monoclonal antibody targeting with recombinant interferon and cytokines.

Up to now a number of studies have been performed to determine whether the combined use of cytokines and monoclonal antibodies (MAbs) directed against tumor-associated antigens (TAA) can increase the sensitivity of radioimmunoscintigraphy (RIS). It is well known that human natural and recombinant interferons can enhance the cell surface expression of HLA Class I and II antigens as well as some specific tumor antigens, but there is scanty and conflicting information about the expression and shedding of TAA. Some authors reported that alpha-IFN enhances the expression of a melanoma-associated antigen (MAA), recognized by conventional antiserum. Other authors have found no changes in the expression of MAA identified by MAbs. In a pilot study on patients with malignant melanoma Rosenblum demonstrated an increase in tumor uptake of the anti-melanoma MAb 96.5 after IFN administration. In our study we performed immunoscintigraphy with the anti-melanoma MAb 225.28S in the same patient before and after IFN administration in different doses. We point out the difference in biodistribution in different organs and in blood clearance and discuss the possibility to improve the sensitivity of RIS.

Antibodies, Monoclonal↗
PubMedDate not supplied

Single determination of CA 15.3 and bone scintigraphy in the diagnosis of skeletal metastases of breast cancer.

Single determination of CA 15.3 and bone scintigraphy were performed on the same day as follow-up procedures in 864 patients with breast cancer. The sensitivity and specificity of bone scintigraphy for skeletal metastases were 99% and 88.8%, respectively. The overall sensitivity and specificity of CA 15.3 (cut-off for pathological values greater than 30 U/mL) for cancer recurrence or distant metastases were 69.2% and 92.1%, respectively. The sensitivity of CA 15.3 for bone metastases was lower (69.4%) than that of bone scintigraphy. This was mainly due to the relatively high proportion of false-negative CA 15.3 levels in patients with 1-2 bone metastases (sensitivity = 33.3%). According to this result, the circulating levels of CA 15.3 showed a good correlation with tumor extension and, in patients with bone metastases, with the number of skeletal lesions. As regards the contribution of CA 15.3 to the diagnosis of bone metastases, the demonstration of elevated CA 15.3 values in patients with positive bone scintigraphy could support the diagnosis of skeletal metastases. In fact, the positive predictive value of CA 15.3 in patients with positive bone scintigraphy was significantly higher than with only bone scintigraphy (53.8%) or CA 15.3 (50.4%). Finally, very high values of CA 15.3 in patients with known bone metastases could indicate the presence of visceral metastases (mean CA 15.3 in patients with bone metastases = 125.8 U/mL; mean CA 15.3 in patients with bone and visceral metastases = 420.5 U/mL).

Adult↗