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Biomedical subjects

F Zito

Publications and source records attributed to F Zito.

At least 19 recordsLinked to original sources

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

[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

Effects of long rise time stimuli on the latencies of the slow V potentials.

Tone bursts with 5, 250 and 500 msec rise time and 70 dB HL (ISO) intensity at the plateau were used to evoke the slow V potentials in ten adults. The mean prolongations of the latencies have been determined and correlated with the subjective auditory thresholds, obtained before each test by conventional push-button audiometry. In normal-hearing subjects our results show a prolongation of the latencies of the slow V potentials when stimuli with longer rise time were used. In subjects with elevated auditory thresholds an almost linear correlation was found between the prolongations of the latencies and the subjective auditory thresholds.

Acoustic Stimulation

MRI, antibody-guided scintigraphy, and glucose metabolism in uveal melanoma.

To evaluate the usefulness of structural and biochemical imaging techniques for the diagnosis of uveal melanoma, 12 patients with choroidal melanoma were examined. Magnetic resonance imaging was used in 11 of 12 patients, as one had a metal prosthesis. All the subjects underwent single photon planar scintigraphy (SPPS) and single photon emission computed tomography (SPECT) using the 99mTc-labeled F(ab')2 of the anti-melanoma monoclonal antibody 225.28S ([99mTc]MoAb) and positron emission tomography (PET) using [18F]fluorodeoxyglucose ([18F]FDG). Magnetic resonance identified 6 of 11 melanotic lesions (definite melanomas) and 4 of 11 hypomelanotic lesions (probable melanomas), whereas in one case it was inconclusive. [99mTc]MoAb uptake was observed in 5 of 12 lesions using SPPS and 8 of 12 lesions using SPECT. [18F]FDG uptake was observed in 3 of 12 lesions by PET. These results demonstrate that both MR and radioimmunoscintigraphy are sensitive techniques for the diagnosis of choroidal melanomas and suggest that the detection of melanomas by MR, SPPS, and SPECT is largely dependent upon their size. The validity of these conclusions was verified in four subjects in whom the diagnosis was based on MR and/or SPECT findings only and confirmed by histology. The finding that only some of the uveal melanomas of larger size are visualized based on [18F]FDG uptake suggests that melanomas can have either high or low glucose consumption.

Choroid Neoplasms

[Interaction between continuous and impulse noise: anatomic and functional evaluation in relation to the intensity of the exposure].

Interaction between continuous and impulse noise was studied. One group of chinchillas was exposed to octave band of noise of 0.5 kHz 95 dB SPL intensity. Three groups were exposed to impulse noises of 113, 119 and 125 prak SPL emitted at 1 imp/sec, 1 imp/4 sec and 1 imp/16 sec respectively. Three groups were exposed to noise created by a combination of above continuous and impulse noises. All exposures lasted for 5 days. Hearing thresholds were measured in 35 animals using auditory evoked potentials. The combined continuous and impulse noises showed equal energy contents, but the groups exposed to 119 and 125 dB impulse noise intensities developed an exacerbation of PTS and cell hair loss. Therefore, the critical level, under which the damage associated with noise exposure is related to the total noise energy (Equal Energy Hypothesis) was reduced when impulse noise was added to continuous noise.

Animals

A new method for faster blood clearance in radioimmuno-guided surgery.

A major inconvenience of intraoperative tumor detection with radiolabeled monoclonal antibody (MoAb) by means of a probe is the long interval needed between the injection of MoAb and surgery (at least 20 days). We describe a new method which entails injection of 125I-labeled biotinylated monoclonal antibodies and cold avidin in order to obtain a rapid blood clearance of the radiotracer. The first clinical application of this protocol has been carried out in a colon cancer patient operated on six days after the administration of 125I-labeled biotinylated MoAb and cold avidin, with an optimal tumor-to-normal tissue ratio and with 90% of the circulating radioactivity cleared in two days.

Abdominal Neoplasms