PubMed Health⌕ Search

Biomedical subjects

G Paganelli

Publications and source records attributed to G Paganelli.

At least 109 records · Page 6Linked to original sources
PubMed1994

Immunoscintigraphy with three step monoclonal pretargeting technique in diagnosis of uveal melanoma: preliminary results.

Several problems still limit the full use of the diagnostic potential of immunoscintigraphy (IS) with technetium-99m labelled monoclonal antibodies (MoAbs) 225-28S directed to high molecular weight melanoma associated antigen (HMW-MAA). The principal problem is the unfavourable ratio of tumour to non-tumour activity (T/nT), due to the poor tumour uptake and the high aspecific uptake of the tissue surrounding the tumour. Recently, it was demonstrated that using the tumour pretargeting technique based on the injection of monoclonal antibody and the avidin/biotin system (three step immunoscintigraphy), an improvement in the T/nT ratio can be obtained in patients with carcinoembryonic antigen secreting tumours. The aim of this study was to compare the diagnostic sensitivity of traditional immunoscintigraphy with that of three step immunoscintigraphy in seven patients with uveal melanoma. All the patients underwent immunoscintigraphy with MoAb 225.28S radiolabelled with technetium-99m, and a three step immunoscintigraphy 1 week later. No patients demonstrated immediate toxic effects after receiving the reagents, no matter which of the two methods was used. The traditional immunoscintigraphy had a diagnostic sensitivity of 71.4%, diagnosing five out of seven melanomas tested. The three step study detected all the melanomas examined (7/7) with a diagnostic sensitivity of 100% and showed a drastic reduction in background. The preliminary results confirm the feasibility of visualising the uveal melanoma and show that the three step immunoscintigraphy is more diagnostically sensitive than traditional immunoscintigraphy, particularly in small lesions.

Aged↗
PubMed1994

Rest distribution of 99mTc-MIBI in patients with coronary artery disease assessed by SPECT: comparison with the distribution of [18F]FDG assessed by PET.

The distribution of 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI), assessed by single photon emission computed tomography (SPECT) was compared to the distribution of 2-[18F]-2-deoxy-D-glucose ([18F]FDG) assessed with positron emission tomography (PET) under fasting conditions, in 21 patients with coronary artery disease (CAD) and severe left ventricular dysfunction in order to evaluate the potential usefulness of SPECT/99mTc-MIBI for the identification of viable myocardium. Stress and rest SPECT/99mTc-MIBI studies were scored based on the percent of 99mTc-MIBI uptake defined by semi-quantitative circumferential-profile analyses. PET metabolic studies with [18F]FDG under fasting conditions, were adopted as a standard of viability. The results of the comparison of 99mTc-MIBI and [18F]FDG distribution showed that among the segments with stress hypoperfusion, [18F]FDG uptake was present in 95% of the segments that had > 40% of the peak tracer uptake at the rest SPECT/99mTc-MIBI study. [18F]FDG uptake was also present, however, in 25% of the segments that had < 40% uptake at the rest SPECT/99mTc-MIBI scintigraphy. We conclude that in patients with CAD the pattern of 99mTc-MIBI distribution appears to underestimate the extent of viable myocardium but only in those regions that are very severely hypoperfused.

Aged↗
PubMed1994

Human biodistribution, dosimetry and clinical use of technetium(III)-99m-Q12.

UNLABELLED: Technetium(III)-99m-Q12, trans-(1,2-bis(dihydro-2,2,5,5-tetramethyl- 3(2H)furanone-4-methyleneimino)ethane)bis(tris(3-methoxy-1-propyl) - phosphine)technetium(III)-99m, is a nonreducible complex of Tc(III) which is herein evaluated as a myocardial perfusion imaging agent. METHODS: The biodistribution and dosimetry of 99mTc-Q12 were assessed in 10 normal volunteers, while its potential clinical use was evaluated in 70 patients. RESULTS: Safety parameters measured up to 24 hr postinjection demonstrate no clinically significant drug-related adverse reactions. Technetium(III)-99m-Q12 exhibits good heart uptake (2.2% injected dose at 1 hr postinjection under resting conditions) and no detectable myocardial washout or redistribution up to 5 hr postinjection. The biodistribution is characterized by very rapid hepatobiliary clearance which allows effective myocardial imaging at times as short as 15 min postinjection. Blood and plasma clearances and myocardial uptake are rapid, while lung uptake is minimal. The heart-to-lung and heart-to-liver ratios are higher at stress than at rest, independent of the time elapsed between injection and image acquisition, and independent of whether the patient is fasted or fed after tracer administration. A preliminary correlation shows that 46/47 patients with angiographically demonstrated CAD also have perfusion defects demonstrated by 99mTc-Q12. CONCLUSIONS: On the basis of the studies reported herein, 99mTc-Q12 appears to be a promising myocardial perfusion imaging agent.

Adult↗
PubMed1994

Radioimmunoguided surgery using iodine-125-labeled biotinylated monoclonal antibodies and cold avidin.

UNLABELLED: One of the limitations of intraoperative tumor detection with radiolabeled monoclonal antibody (Mab), by means of a gamma-detecting probe (GDP), is the long time interval needed between Mab injection and surgery to obtain low blood-pool activity. Such an interval can be shortened considerably, exploiting the high affinity between avidin and biotin. METHODS: Twenty patients with colorectal cancer were injected with 1 mg of biotinylated 125I monoclonal antibodies followed, 48 hr later, by a chase of cold avidin. During surgery, the GDP was used to detect radioactive emissions from the tumor and normal tissue. Tumor tissue samples were analyzed in vitro by immunohistochemical tests for the presence of tumor antigens and in vivo antibody localization. RESULTS: At the time of surgery (average 7 days postinjection), the mean value of circulating radioactivity was 6% +/- 3% of the injected dose. Of 20 patients studied, tumors were localized in 13 cases (65%). Subclinical tumors were detected in 3 patients (15%). CONCLUSION: The use of 125I-labeled biotinylated Mabs followed by avidin as a chase enhances the applicability and effectiveness of radioimmunoguided surgery technology and will allow the use of radioisotopes with a shorter half-life than 125I.

Antibodies, Monoclonal↗
PubMed1993

Egg-related Salmonella enteritidis, Italy, 1991.

In recent years, Salmonella enteritidis has become an increasingly important public health problem in Italy. In some parts of the country, the fraction of total human salmonella isolates accounted for by S. enteritidis has risen from 3-4% in the mid-1980s to more than 30% in 1990. Between 1990 and 1991, the number of reported S. enteritidis outbreaks increased more than sixfold. The 33 outbreaks reported in 1991 occurred in seven contiguous regions in northern and central Italy and were clustered in time between June and October: in the majority, products containing raw or undercooked shell eggs were implicated. Five of the egg-related outbreaks that occurred within a 30 kilometre radius over a 7-week period were investigated in detail. A phage type 1 strain containing a 38.9 MDa plasmid appeared responsible for three of the outbreaks, while in the remaining two a phage type 4 strain, also with a 38.9 MDa plasmid was isolated. Efforts are being made to enhance epidemiological surveillance and laboratory evaluation, and the use of pasteurized eggs has been recommended for high-risk populations.

Disease Outbreaks↗
PubMed1993

Localization of biotinylated monoclonal antibodies (B72.3 and F023C5) in patients with colorectal cancer.

The recognition and treatment of neoplastic lesions in early phases are among the most important aims of research using monoclonal antibodies (MoAb). Recent studies have demonstrated that the use of radiolabelled MoAb directed against tumor associated antigens and hand-held gamma detecting probe (GDP) could help in the recognition of primary tumors and metastases. The goal of this study was to investigate the in vivo antibody reaction as shown by histologic preparations after injection of 125I biotinylated MoAb (B72.3 or F023C5) before surgery and to compare the immunohistochemical results with those obtained with GDP in colorectal cancer. We studied 15 cases of patients with primary or recurrent colorectal cancer. The biotinylated, radiolabelled antibody administered in vivo could be seen in frozen sections with streptoavidin peroxidase complex. In 14 cases there was agreement between GDP observations and detection of the in vivo injected biotinylated MoAb with direct staining using streptoavidin peroxidase conjugate. The use of MoAbs thus provides a means of correlating the intraoperative signal with the presence of the injected antibodies on the tumor.

Antibodies, Monoclonal↗
PubMed1993

Three-step tumor pre-targeting in lung cancer immunoscintigraphy.

Radiolabelled MoAbs have been used in both the diagnosis and the treatment of a variety of tumors. Recently, a three-step tumor pre-targeting strategy has been proposed to overcome one of the major limiting factors in radioimmunodetection: the low tumor-to-background ratio. We evaluated this pre-targeting protocol in 10 patients diagnosed as having pulmonary carcinoma. One milligram of biotinylated anti-CEA MoAb (FO23C5) was administered i.v. (1st step); 24 hours later 5 mg of avidin was injected i.v. (2nd step) followed by 100-500 ng of 111In-biotin (5 mCi) the day after (3rd step). Imaging was performed using single photon emission tomography (SPET). No toxicity and no adverse reactions were observed. Tumor was detected in 8 out of 10 patients. Mediastinal metastases were also localised in 2 out of 3 patients, and adrenal gland recurrency in 1 out of 2 patients. The tumor/background (normal lung), heart, liver and spine ratios were respectively 2.0, 1.0, 1.3 and 4.1 at 90 minutes post-injection. These preliminary data show that the three-step pretargeting method is safe and allows SPECT tumor localization soon after the injection of the radiolabel. In the future, the use of MoAbs with higher specificity could result in improved tumor-targeting, and in the possibility of lung cancer radioimmunotherapy.

Aged↗
PubMed1993

[Apropos of preventive ophthalmologic interventions in the child population of compulsory school age. Authors' experience].

The results are reported of work carried out during the last five years by the Center of Social Ophthalmology, director Prof. G. Scuderi, which is part of the II Division of the Ophthalmologic Clinic of Rome University "La Sapienza" with the object of trying out together with territorial units a model of preventive intervention acting as a filter for specialized university facilities. In other words, already existing facilities and medical personnel were to be used and trained for specific methods and techniques. From 1985 through 1990, 787 children selected by ophthalmologic screening by school doctors among the compulsory school population of the RM 3 and 5 districts were seen and submitted to periodic checks. This cohort included children aged 5 to 14 without significant differences in sex distribution and with prevalence of the 8 to 10 year olds. Each subject was submitted to complete eye examination including refractometry and orthoptics, color vision, biomicroscopic and ophthalmoscopic examination. The principal findings show that about 36% of subjects examined have a natural vision of 11/10 while the high percentage of ametropia observed was mainly represented by astigmatism and hypermetropy, albeit of minor intensity. Strabismus was found in 2.79% and implied marked visual deficit that was often refractory to any type of treatment. In addition, the prevalence was determined of other abnormalities concerning eye motility, color vision and pathologies involving anterior segment and eyeground. In their conclusion, the authors stress the rarity of organic ocular pathology in children (mostly represented by inflammatory changes of the adnexes and conjunctiva) whereas amblyopia was one of the main causes of visual deficit in children. They stress the importance of early therapeutic intervention in order to allow complete visual rehabilitation. The results of the clinical model for prevention were excellent so that it can even be proposed for large scale prevention of amblyopia.

Adolescent↗
PubMed1993

Joint uptake and body distribution of a technetium-99m-labeled anti-rat-CD4 monoclonal antibody in rat adjuvant arthritis.

Joint uptake and body distribution of a 99mTc-labeled monoclonal antibody (Mab) to the rat CD4 molecule (W3/25; IgG1) were investigated after intravenous injection in normal rats and in animals with experimentally induced adjuvant arthritis. An isotype-matched Mab with irrelevant specificity (anti-human carcino-embryonic-antigen) was used as control. A 4 hr sequential gamma-camera imaging revealed that both anti-CD4 and control Mab accumulated to a higher degree in arthritic than in normal ankle joints; the accumulation was comparable for the two Mabs. In contrast to the inflamed joints, a specific accumulation of the anti-CD4 Mab was found in organs rich in CD4-positive cells, i.e. spleen, bone marrow and lymph nodes, as assessed by direct well counter measurements 16 hr after injection. The control Mab displayed no preferential organ accumulation in either normal or diseased animals. These results indicate that a specific accumulation of anti-CD4 Mabs occurs in CD4-positive-cell-rich tissues in both normal and diseased animals and that immunoglobulins accumulate preferentially in inflamed joints regardless of their antibody specificity.

Animals↗
PubMed1992

Presurgical identification of hibernating myocardium by combined use of technetium-99m hexakis 2-methoxyisobutylisonitrile single photon emission tomography and fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography in patients with coronary artery disease.

We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗
PubMed1992

Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin.

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3-5 days later by 100-150 micrograms of indium-111 streptavidin, at the specific activity of 280-370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1-8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1-30:1) and 45:1 (range 12:1-120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1-30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01-0.3) for recurrences and 0.05 for primary tumour (range 0.005-0.2). Over 24-48 h 14% i.d. (range 8-18% i.d.) was found in the urine, 14% i.d. (range 6-29% i.d.) in the blood and 63% i.d. (range 56-70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer.

Bacterial Proteins↗
PubMed1991

Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients.

We describe a method to postlabel, in vivo, biotinylated monoclonal antibodies pretargeted onto tumor deposits when most of the non-tumor-bound antibodies have already been cleared as avidin-bound complexes. The application of this principle to tumor detection by immunoscintigraphy was tested in 20 patients with histologically documented cancer and increased circulating carcinoembryonic antigen levels. One mg of biotinylated anti-carcinoembryonic antigen monoclonal antibody (FO23C5) was administered i.v. (first step). After 3 days, 4-6 mg of cold avidin were injected i.v. (second step), followed 48 h later by 0.2-0.3 mg of a biotin derivative labeled with 111In (2-3 mCi) (third step). No evidence of toxicity was observed. Whole body radioactivity distribution was measured in five patients at various intervals postinjection by the conjugate counting technique. Tumors and metastases were detected in 18 of 19 patients (the remaining patient was a true negative) within 3 h after administration of 111In-biotin by planar or single photon emission tomography imaging. At the time of imaging, tumor/blood pool ratio was 5.5 +/- 3.2, and tumor/liver ratio was 6.7 +/- 3.9. Blood clearance of 111In-biotin was multiexponential, with the fast component having a t1/2 of 5 +/- 3 min. Urinary excretion of radioactivity over 3 h was 63.5 +/- 4.9% of the injected dose. Radioactivity at 3 h was 6.5 +/- 1.8% in blood, 1.6 +/- 0.3% in the kidney, and 2.4 +/- 0.6% in the liver. This approach represents an improvement in immunoscintigraphic techniques for tumor localization. The potential use for radioimmunotherapy is discussed.

Antibodies, Monoclonal↗
PubMed1991

Surgery for colorectal cancer guided by radiodetecting probe. Clinical evaluation using monoclonal antibody B72.3.

Radioactive antibodies that react with tumour-associated antigens to "tag" antigen-positive tumour cell deposits were given to 20 patients with primary or recurrent colorectal cancer. The tumour associated antigen TAG 72-specific monoclonal antibody B72.3 labelled with 125-Iodine was used, and the radioactivity in the tumour was sought during operation with a hand-held gamma detecting probe. Tumour was detected by the probe in 7 of 15 patients with primary cancer, with a mean tumour: normal tissue ratio of 3.9, and in 4 of 5 patients with recurrent disease, with a mean tumour: normal tissue ratio of 2.0. Immunohistochemical analysis of surgical specimens confirmed the results of the intraoperative detection. The incidence of TAG 72-positive tumours (11/20, 55%), detected by immunohistochemistry, was lower than the 80% in the other series, possibly because of sampling errors or because the cases studied were uncomplicated with small primary tumours. Results obtained with the probe were instrumental in modifying the operation in two of the four "positive" patients with recurrences, allowing the removal of tumour masses that would otherwise have been overlooked.

Adenocarcinoma↗
PubMed1990

Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies.

We describe 2-step and 3-step strategies for intraperitoneal tumor radio-localization by means of monoclonal antibodies (MAbs). Nude mice bearing intraperitoneal human colon carcinoma tumors were injected i.p. with biotinylated MAb AUAI, followed 24 hr later by radioiodinated streptavidin (2-step). The uptake of radioactivity in tumor and normal tissues was measured 4 hr after injection of radioactive compound. A 3-step strategy consisted in administering biotinylated antibody, cold avidin after 24 hr and 111In-labelled biotin after a further 4 hr; mice were then killed 2 hr later. Tumor localization of intraperitoneally-administered biotinylated antibody and direct targeting of radioactive streptavidin to biotinylated antibody bound to tumor sites were demonstrated using immunohistochemistry and autoradiography. Our results show that (i) the 2-step approach increased the percentage of radioactivity uptake by tumor with respect to directly labelled antibodies (24% vs. 6%) and improved the tumor/non-tumor ratio; (ii) the 3-step approach allowed faster blood clearance of the radioactive probe (111In-biotin) and yielded high tumor/non-tumor ratios. "Pre-targeting" methods appear to have advantages over the conventional 1-step approach with directly radiolabelled antibody.

Animals↗