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Biomedical subjects

L Maffioli

Publications and source records attributed to L Maffioli.

At least 19 recordsLinked to original sources
PubMed2003

Effect of an intensive chemotherapy followed by mediastinal irradiation on pulmonary and cardiac function in advanced Hodgkin's disease.

Mediastinal irradiation combined with chemotherapy in patients with Hodgkin's disease have been associated with cardiopulmonary toxic effects that can last over the years. In this study we monitored pulmonary and cardiac function in 39 patients affected by advanced Hodgkin's disease (stage II B-III and IV) with mediastinal involvement and submitted to an intensive chemotherapy regimen (epirubicin, vincristine, ciclophosphamide, and etoposide) followed by involved field irradiation. Pulmonary function was verified with chest x-ray, spirometric parameters, arterial blood gas analysis, single breath CO transfer factor (DLCO), and its components Dm and Vc. Cardiac function was verified with electrocardiogram (EKG) and left ventricular ejection fraction (LVEF) by means of radionuclide angiocardiography. The median follow-up was 40 months. Spirometric parameters did no show modifications at the end of treatment, on the contrary they improved during the follow-up. Chest x-ray showed radiographic parenchimal damage in 51% of patients. DLCO remained constantly decreased. sEKG did not show significant modification, whereas LVEF significantly decreased at the end of treatment and remained persistently decreased during follow-up. None of the patients with reduction of DLCO or LVEF showed clinical symptoms of heart and pulmonary dysfunctions. One patient, 49 years old, suffered from myocardial infarction 25 months after the completion of radio-chemotherapy. These data indicate that this combined regimen can induce persistent pulmonary and cardiac damages at subclinical level.

Adolescent↗
PubMed2001

Production and validation of the pharmacokinetics of a single-chain Fv fragment of the MGR6 antibody for targeting of tumors expressing HER-2.

The HER-2 antigen, which is overexpressed in many breast carcinomas, is an ideal target for monoclonal antibodies due to its low expression in normal tissue and its homogeneous distribution in the tumor mass. We have developed and characterized the murine MAb MGR6 against HER-2, which is able to inhibit proliferation of tumor cells overexpressing HER-2. On the basis of these preclinical results, phase I studies in breast carcinoma patients were conducted and radiolocalization data indicated an antibody half life which directly paralleled that of other whole antibodies and thus resulting in a limited in vivo diagnostic capacity. To obtain a smaller reagent with possibly improved in vivo properties, a single chain variable fragment (scFv) of the original MGR6-producing hybridoma was generated by phage display technology. Biologically active MGR6 scFv was purified rapidly and at high yield by metal affinity chromatography. Competition FACS and ELISA analyses identified an epitope on the HER-2 extracellular domain that was shared by the scFv and the parental MAb. BlAcore analysis indicated a Koff of 9.3 x 10(-4) s(-1), similar to that of the intact MGR6 MAb. Distribution and elimination half-lives of MGR6 scFv, calculated from in vivo preclinical evaluations, were much faster (13 min and 6.2 h, respectively) than previously published results for the intact MAb (mean t1/2beta of 46 h). This represents a theoretical improvement in pharmacokinetics with respect to the parental murine MAb and points to the potential for utilizing this fragment in redirecting therapeutic agents, such as radioisotopes, to different human carcinomas overexpressing HER-2.

Amino Acid Sequence↗
PubMed2001

Bone scintigraphy and the added value of SPECT (single photon emission tomography) in detecting skeletal lesions.

Skeletal metastases are one of the major clinical problems for the oncologist. Over the last several decades bone scintigraphy has been used extensively in detecting bone involvement since it can provide information about disease location, prognosis and the effectiveness of treatment. Bone scan offers the advantage of total body examination, and images bone lesions earlier than other techniques. In this paper the main clinical problems related to the most common applications of bone scan in breast, prostate, lung cancer and other tumours are discussed. The experience carried out at the National Cancer Institute of Milan by using bone SPECT to detect single bone metastases is reported. One hundred and eighteen patients with bone metastases (from different tumour types: breast, lung, prostate, lymphomas, etc.) were studied by planar scintigraphy, SPECT and other radiological modalities (CT, MRI or X-rays). The overall performances of bone SPECT were sensitivity: 90.5% (19/21), specificity 92.8% (90/97), positive predictive value 73% (19/26), negative predictive value 97.8% (90/92), accuracy 92.4% (109/118). Considering breast cancer, the most frequent pathology in our series, and the lumbar spinal tract, the most common skeletal segment involved, the figures of merit of SPECT were: sensitivity 100% (4/4), specificity 95.3% (41/43), positive predictive value 66.7% (4/6), negative predictive value 100% (41/41), accuracy 95.7% (45/47). In conclusion bone SPECT showed very good performances, in particular improving the predictive value of planar scan in the diagnosis of vertebral metastases.

Bone Neoplasms↗
PubMed1999

Current applications and perspectives of diagnostic nuclear medicine in oncology. Task Group of Oncology.

The characteristic of nuclear medicine is that it gives images of organs, structures and physiological or pathological processes, detecting the distribution of several radio-pharmaceuticals according to their uptake and metabolism. Its imaging can provide morphological information while at the same time containing data on cellular activity and functions. Such molecular imaging fulfils the modern orientations of oncology, where there is a need to define the presence of a malignancy in the earliest and most effective way, to characterise the neoplasm in terms of biological characteristics (e. g., proliferation, aggressiveness, differentiation, receptor status) and to obtain fundamental issues in patient management such as evaluation of disease extent, monitoring of therapies and study of treatment-induced side effects. The aim of this position paper is to discuss the main indications of nuclear medicine in diagnostic oncology reporting the most recent developments in nuclear medicine, and an extensive list of the major indications for nuclear medicine procedures. The techniques have been labelled as when considered essential in the diagnostic process, when they can give useful additional or information in combination with other instrumental diagnostic approaches, and alternative when they may be performed instead of other tests. These indications were derived by a general consensus within the Task Group of Oncology of the World Federation of Nuclear Medicine and Biology, and it should be stressed that only the current role of nuclear medicine was considered. The Task Group does not claim to have covered the entire range of nuclear medicine indications; in fact it was agreed to include only the most widely used techniques. The highly specific or very exceptionally used applications, or those still in development or under evaluation in clinical trials were not taken into consideration. The conclusion is that the current relationship between nuclear medicine and oncology can be defined not only as satisfactory but also as extremely promising, as nuclear medicine has the potential to compete with the most advanced radiological techniques of imaging, perhaps not so much in terms of sensitivity but more so in terms of specificity and biological characterisation. Several novel diagnostic procedures are able to solve clinical problems for which traditional radiology has shown clear limitations. Nuclear medicine remains today a dynamic medical specialty because it includes a combination of advances in basic science research, technology, cell biology and medical practice and it cannot be excluded that the new lines of research both towards new radiopharmaceuticals and advanced instrumentation will offer in the future new stimulating opportunities.

Forecasting↗
PubMed1998

Nuclear medicine approaches for detection of axillary lymph node metastases.

In breast cancer patients the detection of axillary lymph node involvement is a very critical issue, in view of the earlier diagnosis of the disease in recent years, and the increased frequency of very small tumors at first presentation. The size of cancer is related to the risk of axillary metastases, and this may affect the prognosis and the therapeutic strategies. Axillary lymph node involvement is generally recognized as an index of distant microdiffusion, and as it affects overall and disease-free survival, represents the basis for adoption of adjuvant chemotherapy. Routine axillary lymph node dissection (ALND) is expensive, and does not benefit about 70% of early breast cancer patients which are node negative (pN-). Today most of these patients have to sustain the potential morbidity and the economic costs of ALND. The clinical approach is known to be an unreliable diagnostic tool, and for the detection of axillary metastases, conventional X-ray techniques are also unable to solve the problem. By contrast, nuclear medicine procedures have revealed a very interesting diagnostic potential in recent years. This paper analyzes the numerous studies conducted in the field of lymph node visualization and the heterogeneity of the published experiences, taking into account the different approaches proposed in the literature: a) imaging with gamma-emitting tumor seeking agents; b) radioimmunoscintigraphy intravenous (i.v.) or by the interstitial route; c) lymphoscintigraphy with colloids and gamma probe sentinel biopsy; d) positron emission tomography (PET). Although it is very difficult to make a definitive statement about the clinical efficacy of all these methods, this paper reports the most important series of patients examined in the literature as well as the author's own experiences. This can serve as the basis for a better understanding of the potential of nuclear medicine procedures, and gives the reader the opportunity to weigh advantages and drawbacks of each method. At present, lymphoscintigraphy with gamma probe sentinel biopsy and FDG-PET are the nuclear medicine approaches with the best diagnostic performance. However, a correct comparison of the methods will not be possible, until their careful assessment in the same patients is performed. In addition, a final statement today should consider also the increasing need to carry out an economic analysis by evaluating the cost-effectiveness of the examinations.

Axilla↗
PubMed1998

Gallium-67 scintigraphy evaluation of therapy in non-Hodgkin's lymphoma.

UNLABELLED: Patients with diffuse large cell lymphoma may achieve complete remission (CR) after chemotherapy, and the time to reach CR may be predictive of treatment outcome. Partial remission, or recurrence from CR, is associated with poor survival. Gallium-67 imaging has proven to be useful in evaluating lymphoma patients. In tumor models, this radiotracer is an indicator of tumor viability. Gallium-67 uptake is seen only in avid and viable lymphoma tissue, not in fibrotic or necrotic tissue. In this study, we prospectively assessed the ability of this radiotracer to define residual disease. In addition, we evaluated the possibility of predicting the clinical outcome in patients with diffuse cell lymphoma on the basis of scan positivity during chemotherapy. METHODS: Thirty-three consecutive patients with histologically proven diffuse large cell lymphoma were investigated with 67Ga scintigraphy 48-72 hr after injection of 185-259 MBq 67Ga-citrate for staging and during follow-up after four to six cycles of intensive chemotherapy. Patients were monitored for a mean of 56.0 mo (range 7-90 mo), and they were restaged using physical examination, CT and all necessary imaging modalities. RESULTS: Patients were divided into two groups according to the positivity or negativity of 67Ga scan after four to six cycles of chemotherapy. Of the 33 patients studied, 14 (42.4%) showed persistent abnormal uptake of 67Ga-citrate after four to six cycles of chemotherapy. In this group, 9 patients (64.2%) died of lymphoma at a mean of 24.3 mo from presentation with the diagnosis (range 7-71 mo). Four patients had no evidence of disease at an average of 71.7 mo after diagnosis, and 1 patient was considered to be in partial remission. In the second group of 19 67Ga-negative patients, after four to six cycles of chemotherapy, 4 died and 15 are alive and considered to be in CR. A statistical analysis of the association between 67Ga scan results after four to six cycles of chemotherapy and survival was performed using the log-rank test; there was a statistically significant association between scan results and survival (p=0.00125). CONCLUSION: We conclude that 67Ga scintigraphy is an excellent predictor of residual tumor viability in lymphoma patients and that persistent positivity of the scan predicts poor outcome and may justify a change in treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Comparison of three different methods for radiolabelling human activated T lymphocytes.

One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.

Cell Death↗
PubMed1997

Comparison of gallium scan, computed tomography, and magnetic resonance in patients with mediastinal Hodgkin's disease.

BACKGROUND: In patients with Hodgkin's disease, the use of gallium-67 scintigraphy (Ga-67) compared to conventional staging and restaging techniques is still controversial. In particular, in a combined modality treatment with chemotherapy and radiotherapy given in sequence, its role in detecting active disease after chemotherapy may be useful in planning the subsequent radiotherapeutic strategy. PATIENTS AND METHODS: From March 1990 to September 1994, 125 patients with previously untreated histologically proven Hodgkin's disease were enrolled in two different prospective trials according to clinical stage. Staging procedures included Ga-67, chest-abdominal computed tomography (CT), and/or magnetic resonance (MR). All three tests were performed in 53 patients at staging and in 47 at restaging. Results of Ga-67 at staging were compared to conventional procedures or pathological findings. Results of Ga-67, CT scan, and MR at restaging were compared to disease outcome during the follow-up. Finally a cost/benefit ratio for each test was determined. RESULTS: At staging, Ga-67 showed lower sensitivity than CT and MR (90 vs. 96 and 100%, respectively) because of the number of false-negative images. Nevertheless, by using both CT and Ga-67 scan, the sensitivity is equal to that observed with MR (100%). At restaging, Ga-67 is superior to CT scan and equivalent to MR in detecting true negative patients (specificity: 98% vs. 45% vs. 92%). CONCLUSIONS: As a single technique, Ga-67 scan cannot substitute for CT scan or MR in staging patients with Hodgkin's disease. Nevertheless, Ga-67 scan has an important role in defining complete remission after treatment and therefore in planning subsequent treatment. Considering the lower costs of CT scan plus Ga-67 ($320) versus MR alone ($810), the two tests may be considered procedures of choice in staging as well as in restaging patients with Hodgkin's disease.

Adult↗
PubMed1997

Breast cancer seeking agents: basic approach.

The knowledge of biochemical and physiological mechanisms involved in tissue localization is important so as to understand the information given by diagnostic nuclear medicine imaging, and eventually to design new radiopharmaceuticals. The cellular mechanisms which permit a high cancer uptake involve the perfusion and metabolism around the tumour tissue, the interference with normal function, the altered perfusion and/or metabolism within the tumour. All these phenomena can contribute to a high concentration of particular radiotracers in cancer and can create a favourable tumour/background ratio uptake sufficient for cancer imaging. Those molecules might be also powerful tools for reaching an advanced understanding of neoplastic and even "normal" cell biology. During these last years, some radiotracer specifically designed for different applications proved to be promising radiopharmaceuticals for breast cancer imaging. This is the case of monoclonal antibodies (Mabs) developed in the past against membrane cancer antigens. Other tracers, originally proposed for the study of vascular perfusion (cardiovascular tracers), have also revealed a capacity to be taken up by cancer cells. The radiopharmaceuticals mostly used as tumour seeking agents today (Radiothallium, Sestamibi, Tetrophosmin) were generated with other applications in mind. In this paper we review the mechanisms of uptake of the most relevant agents currently proposed for breast cancer imaging, including 18F-fluorodeoxyglucose (FDG). The radiotracers will be examined on the basis of the available scientific evidence regarding their cellular uptake and release. Moreover, we report our preliminary studies on the cellular uptake and release of these and other compounds recently introduced in clinical trials.

Breast Neoplasms↗
PubMed1996

Clinical role of technetium-99m sestamibi single-photon emission tomography in evaluating pretreated patients with brain tumours.

One of the main problems regarding the follow-up of patients with brain tumours treated with radiotherapy is the distinction between radiation necrosis and tumour relapse. In many cases computed tomography (CT) scan is unable to distinguish between the two. We assessed the usefulness of brain single-photon emission tomography (SPET) with technetium-99m-sestamibi in cases where CT scan was not conclusive. The absence of tracer uptake in normal brain, the sharp uptake in neoplastic tissue, and the favourable physical properties of technetium make the scintigraphic method particularly accurate. We therefore propose the association of CT scan with 99mTc-sestamibi brain SPET in the follow-up of patients in whom a distinction between radiation necrosis and active disease is needed for an adequate therapeutic decision.

Adolescent↗
PubMed1996

Comparing reconstruction with Roux-en-Y to a pouch following total gastrectomy.

BACKGROUND: Although more than 50 methods of gastric replacement after total gastrectomy have been used, none of them has demonstrated a substantial nutritional advantage. The Roux-en-Y esophagojejunostomy is still the preferred type of reconstruction, more because of its simplicity than the lack of postprandial disturbances. STUDY DESIGN: A randomized controlled trial was conducted to compare two reconstructive procedures, Roux-en-Y esophagojejunostomy (n = 24) and Hunt-Rodino-Lawrence pouch (HRL, n = 24), by evaluating nutritional status (body weight, arm circumference, and serum nutritional parameters), nutritional habits (number of meals, energy intake, and postprandial disturbances), and emptying time of the jejunal loop. RESULTS: Twenty-seven patients were studied two years after operation (12 had undergone Roux-en-Y and 15 had undergone HRL). No difference was found in either postoperative morbidity or mortality, emptying time, frequency of meals, or variation of body weight. Postprandial disturbances were more frequent in patients having Roux-en-Y. In a subset of patients, there was a correlation between nutrient intake and change of body weight, but not between nutrient intake and type of reconstruction. CONCLUSIONS: The simple use of a reservoir such as the HRL pouch after total gastrectomy is of no benefit to the patient as compared with the Roux-en-Y reconstruction.

Anastomosis, Roux-en-Y↗
PubMed1995

111In-DTPA-D-Phe-1-octreotide scintigraphy of small cell lung cancer.

Twenty-one patients with small cell lung cancer (SCLC) were investigated with 111in-octreotide (111-In-OCT) scintigraphs, 5 hours after the i.v. injection of 111 MBq of the radiotracer. Whole-body and planar scintigraphy as well as SPECT of the thorax were required. The scintigraphic results were compared to those of other conventional diagnostic procedures used for the staging and follow-up of SCLC patients. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy, being positive for all 20 SCLC lesions and negative for one lung adenocarcinoma. 111In-OCT showed a high sensitivity for mediastinal metastases (94%) and good sensitivity for bone (75%) and abdominal lymph node metastases (71%). It did not detect 2 liver metastases but revealed 5 unknown lesions which were then confirmed by other diagnostic examinations. 111In-OCT was also effective in patients with low levels of NSE. Three patients received cold octreotide for seven days to investigate whether this treatment might affect SCLC imaging. Scans were performed before and after treatment. The 111In-OCT uptake increased in the cancer lesions while the fixation in normal tissues decreased, demonstrating enhancement of SCLC imaging following cold octreotide administration.

Adenocarcinoma↗
PubMed1994

Comparison of radioimmunodetection with other imaging methods in evaluating local relapses of colorectal carcinoma.

BACKGROUND: The prognosis for colorectal cancer patients is related closely to the extent of tumor at the time of diagnosis, and early detection of metastatic or recurrent disease is an important prerequisite for successful treatment. Radioimmunodetection is a relatively new technique to image colorectal cancer using radiolabelled monoclonal antibodies (MoAb). The goal of this study was to evaluate the clinical use of radioimmunodetection with the anti-carcinoembryonic antigen MoAb FO23C5, radiolabelled with 131I, in patients submitted to surgery for colorectal cancer and with suspected local recurrences. The results of radioimmunodetection were compared with those of computed tomography, ultrasonography, magnetic resonance imaging, and other diagnostic techniques (gastrointestinal x-ray, endoscopy, and, in selected cases, a surgical second look). METHODS: Fifty-nine patients with a rise in carcinoembryonic antigen serum levels or a clinical suspicion of recurrences entered the study. Scintigraphy was performed at multiple interval times (4-100 hours) after an intravenous injection of radiolabelled FO23C5 F(ab')2 fragments. RESULTS: The cumulative results showed the high sensitivity (89%), specificity (78%), and accuracy (86%) of radioimmunodetection. Of the radiologic methods, only magnetic resonance imaging had the same accuracy (86%), with lower specificity (64%) and higher sensitivity (93%). Computed tomographic scan and ultrasonography displayed the poorest accuracy (68% and 47%, respectively). CONCLUSIONS: Radioimmunodetection is an important imaging technique that can be used in clinical practice for the follow-up of the patient with colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed1994

Scintigraphic detection of melanoma metastases with a radiolabeled benzamide ([iodine-123]-(S)-IBZM).

UNLABELLED: Iodine-123-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ([123I]-(S)-IBZM) is a radiolabeled benzamide usually employed to study neuropsychiatric disorders, such as schizophrenia and Parkinson's disease. The ectodermic origin of melanocytes and the presence of melanin in the substantia nigra are the theoretic basis of the experimental use of this class of tracers for melanoma imaging. METHODS: Eleven patients with proven metastatic melanoma entered the study. Whole-body and planar scintigrams were performed 2, 4 and 24 hr after intravenous injection of a mean tracer activity of 205 MBq. The dosimetric evaluation was performed by the Medical Internal Radiation Dose Committee method. RESULTS: The [123I]-(S)-IBZM scans allowed the detection of all six cutaneous lesions, five of six superficial pathologic lymph nodes, four of five pulmonary and one of two hepatic metastases. The maximum tumor-to-background ratio was 2.6 in planar images. The hepatobiliary excretion of the tracer may limit detection of intra-abdominal lesions. Dosimetry is similar to data for nononcologic patients. CONCLUSION: Although it is unclear if the mechanism of radiopharmaceutical uptake in melanoma is due to binding to membrane receptors or due to interactions with intracellular structures, radiolabeled benzamide is a promising tracer to detect melanoma.

Adult↗