Search PubMed⌕ Search

Biomedical subjects

F Zito

Publications and source records attributed to F Zito.

At least 55 records · Page 3Linked to original sources

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↗

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↗

High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease: comparison with fluorine-18-FDG PET.

UNLABELLED: SPECT studies of regional cerebral perfusion with a high-resolution system were compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21 patients with probable Alzheimer's disease (AD). Ten normal subjects were also evaluated with SPECT and 10 with PET. METHODS: rCMRglc (for PET) and counts (for SPECT) in the associative cortices were normalized to the average rCMRglc, and counts in the calcarine cortex and basal ganglia were considered as a "reference area" to obtain a ratio. The ratio differences between patients and controls were tested with ANOVA performed separately for PET and SPECT. RESULTS: The difference between probable AD patients and controls was significant for both PET (p < 0.00001) and SPECT (p < 0.005); this difference was significant for the frontal, temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p < 0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were detected in all subjects with PET and in 90% with SPECT. CONCLUSION: PET and SPECT are able to detect characteristic temporo-parietal abnormalities in probable AD. However, the presence of abnormalities in other associative areas is better evaluated with PET.

Adult↗

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↗

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↗

In vivo metabolism and kinetics of 99mTc-HMPAO.

The cerebral distribution of 99mTc-labeled d, l, hexamethyl-propylene-amine-oxime (99mTc-HMPAO) as a function of rCBF and time was examined in rats and in man. The results of this study confirm that 99mTc-HMPAO is distributed in brain in proportion to rCBF. However, the rapid systemic breakdown of the tracer in blood results in considerable difficulties in the assessment of the arterial concentration of the parent compound; incomplete extraction of 99mTc-HMPAO from blood to brain and significant efflux from brain represent further limitations in the use of this tracer for quantification of rCFB. Despite these limitations 99mTc-HMPAO is of potential interest for a qualitative assessment of rCBF in specific clinical conditions.

Animals↗

Scar formation following impulse noise-induced mechanical damage to the organ of Corti.

The terminal stages of the healing process of the organ of Corti in the chinchilla following exposure to blast-waves at 160 dB peak SPL, were studied by scanning electron microscopy (SEM) and by surface preparation technique. Extensive lesions of the sensory epithelia consisting in the absence of the OHC's, Deiter cells and Hensen cells, were replaced by scar tissue formed by single, flat, irregularly polygonal cells, arising from the Claudius cell area sealing off the endolymphatic spaces. When the pillar cells have been destroyed the scar epithelium from the Claudius cells has reached the IHC's, which show a remarkable resistance to acoustic trauma. Their presence in a large healed area may be the only remnants of a previous sensory region. When even the IHC's are absent, the entire organ of Corti can be replaced both by Claudius cells and by inner sulcus cells covering the denuded basilar membrane without any clear morphological difference between the two cellular sources.

Animals↗

The acoustic reflex pattern studied by the averaging technique.

The acoustic reflex threshold and its pattern in response to stimuli of different intensities, were investigated by means of the signal-averaging technique in 20 normal, 20 sensorineural-impaired and 10 successfully stapedectomized ears. Trains of tone bursts between 110 and 0 dB HL were used. The frequencies tested were 500, 1 000, 2 000 and 4 000 Hz. In all normal subjects, the pattern of the acoustic reflex for stimuli between 110 and 100 dB HL was biphasic with an initial positive plateau followed by a longer negative one. For stimuli below 80 dB HL, the pattern of the reflex was monophasic with a single positive peak. In the sensorineural-impaired ears, the same double pattern of the waveform was obtained. In the stapedectomized ears, no compliance changes were observed for any sound stimuli. By the averaging technique, the difference between the acoustic reflex threshold and the auditory threshold was found to be between 7.5 and 32.5 dB, in normal and sensorineural-impaired ears.

Acoustic Impedance Tests↗

[Study of the wave-form of the stapedial reflex in response to sonorous stimuli of different intensity].

The threshold of the acoustic reflex and its pattern in response to different intersity stimuli, was investigated by means of the signal-averaging technique in 10 normal ears. Trains of tone bursts between 100 and 0 dB HL were used. The frequencies tested were 500, 1000, 2000 and 4000 Hz. In all subjects the pattern of the acoustic reflex for stimuli between 110 and 100 dB HL was biphasic, with an initial positive plateau followed by a longer negative one. For stimuli < 80 dB HL the pattern of the reflex was monophasic, characterized by a single positive peak (latency between 120 and 170 msec).

Acoustic Impedance Tests↗

[Pseudocyst of the pancreas fistulized into the right pleural cavity].

The development of a pancreatic pseudocyst which fistulized into the right pleural cavity through a lesion in the diaphragm is described. The case is the 2nd in Italian literature and the 5th in the world. The relationships between pancreatic and thoracic pathology are examined, particularly the various ways in which pancreatic enzymes are spread and transferred to the abdomen and thorax. Such a fistulization phenomenon is the ultimate expression of an erosive process of the pancreatic juice and is considered quite exceptional with respect to the more frequent cases of pleural exudation with high amylase content which are often encountered in concomitance with verified pancreatic pathology.

Female↗