Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of conjugation on the biodistribution of 111In-labelled antibodies was studied in nude mice carrying human prostatic cancer xenografts (PC-82). Two monoclonal antibodies and their fragments raised against human prostate-specific acid phosphatase (PAP) and prostate-specific antigen (PSA) were used. We used the cyclic anhydride of DTPA (CA-DTPA) as a chelating agent, or, alternatively, 1-(p-aminobenzyl)diethylenetriaminepentaacetic acid (NH2-Bz-DTPA) was attached as a linker to the carbohydrate components of the parent molecules. The conjugation method, the amount of circulating antigen and the size of the antibody component affected the blood clearance of the labelled derivatives. F(ab')2 fragments displayed a faster blood clearance than the corresponding derivatives of intact IgG1s. Aminobenzyl derivatives of anti-PAP-IgG1 showed a faster blood clearance than the corresponding CA-DTPA derivatives, but, in the case of derivatives of anti-PSA-IgG1, this was less clear, possibly due to the high PSA concentrations in the mouse sera. All the derivatives studied accumulated in the liver independently of the size of the antibody derivative, most probably due to the formation of antigen-antibody complexes. All CA-DTPA derivatives showed a higher kidney accumulation than the corresponding aminobenzyl derivatives. CA-DTPA-anti-PAP-F(ab')2 fragments showed a higher kidney uptake than the corresponding anti-PSA-F(ab')2 derivatives, since a large fraction of the latter are complexed with circulating antigen, thereby slowing down its reabsorption by the kidney. In addition, the lower kidney accumulation for anti-PSA-F(ab')2 fragments might be, at least partly, due to the electronegative charge of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of conjugation on the biodistribution of 111In-labelled anti-PAP and anti-PSA monoclonal antibodies examined in nude mice with PC-82 human tumor xenografts. 172 16

We evaluated 14 consecutive patients with leptomeningeal metastasis prospectively, using both T1-weighted (T1W) gadolinium-DTPA-enhanced MR (Gd-MR) and contrast-enhanced CT (CE-CT). Thirteen had positive CSF cytology; the remaining patient had an atypical CSF lymphocytosis and primary CNS lymphoma. The patients (8M/6F) ranged in age from 8 to 70 years (median, 42 years). Tumor histology included 3 systemic and 2 primary CNS lymphomas, 3 breast carcinomas, 2 leukemias, 1 malignant schwannoma, 1 small cell lung cancer, 1 prostate cancer, and 1 melanoma. Both imaging methods demonstrated parenchymal volume loss equally well in all patients. Gd-MR revealed abnormal enhancement of meninges or parenchyma in 10 patients, including all 5 patients with positive CE-CT. Neither technique revealed any foci of abnormal enhancement in 4 patients. Gd-MR was superior to CE-CT in demonstrating and quantifying enhancing subarachnoid and parenchymal nodules in 6 patients and in demonstrating sulcal, dural, cisternal, tentorial, and ependymal enhancement. Our findings indicate that T1W Gd-MR is the preferred imaging modality in leptomeningeal metastasis and suggest that CE-CT is unnecessary.
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PMID:Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. 231 84

F(ab')2 fragments (at concentrations of 5-30 mg/ml) derived from monoclonal antibodies raised against human prostate specific acid phosphatase were derivatized with a bicyclic anhydride of diethylenetriaminepentaacetic acid (cDTPAA) in the molar ratios of cDTPAA/F(ab')2 of 1:1, 5:1, 10:1 or 50:1. The most optimal product, aimed at radioimaging of prostatic cancer was obtained when the antibody fragment concentration was at least 10 mg/ml and the molar ratio of cDTPAA to F(ab')2 was 5:1. cDTPAA was added dissolved in dimethylsulfoxide (DMSO). Under these conditions, 1.8-2.2 DTPA molecules/F(ab')2 molecule were bound, giving a coupling efficiency of 37%-44%, and the labelling efficiency with 111In (3 mCi/1 mg protein) was 95% +/- 3% (n = 7). The antibody fragment completely retained its immunoreactivity measured by radioimmunoassay and showed no aggregation when studied using sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). For evaluation of the degree of conjugation of DTPA to the antibody fragment, a novel technique was developed relying on the use of EuCl3, and the measurement of europium fluorescence employing time resolved fluorometry. Results by EuCl3 labelling were identical to those obtained by the conventional 111InCl3 labelling method.
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PMID:Radiolabelling of monoclonal antibodies: optimization of conjugation of DTPA to F(ab')2-fragments and a novel measurement of the degree of conjugation using Eu(III)-labelling. 246 81

We performed MRI in several recent cases of bladder cancer and prostatic cancer using a general coil or a 5-inch general purpose surface coil with or without Gd-DTPA. The surface coil improves the spacial resolution, density resolution and signal to noise ratio but reduces the field and the signal detection drops off as the depth from the surface increases. Moreover, additional time is required for patient positioning. In Gd-DTPA enhanced images of bladder cancer, the muscle layer became more distinct, and the images of tumor and bladder mucosa were enhanced, suggesting that facilitates evaluation of the extent of bladder wall invasion of the tumor. In Gd-DTPA enhanced images of prostatic cancer, the area conside to correspond to the tumor was enhanced. MRI using a surface coil and Gd-DTPA is considered to provide detailed information of bladder and prostatic cancer.
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PMID:[Clinical application of MRI for urological malignancy. 3: A new trial of MRI for bladder cancer and prostatic cancer; surface coil and GD-DTPA]. 323 21

The 111In-labeled monoclonal anti-prostatic acid phosphatase (PAP) monoclonal antibody F(ab')2 fragment was used for the radioimmunodetection of prostate cancer in two different patient groups: 15 patients with surgically verified T1-2 prostate cancer were imaged prior to staging lymphadenectomy and total prostatectomy using lymphatic administration (intraprostatic (ipr) injection), and 15 patients with verified metastatic prostatic cancer were imaged after intravenous (i.v.) injection. The patients were studied on several occasions (at 0-180 hours) after injecting a 1 mg MoAb fragment labeled with 75-150 MBq111In (DTPA-chelation). The extirpated tissues were counted for radioactivity, and studied immunohistochemically (IHC) and histologically. The anti-PAP MoAb was labeled with high efficiency (87-99%) and it demonstrated good immunoreactivity (90-95%) and a high affinity to the target antigen. In the excised prostates, cut into 12-18 smaller pieces, there was a clear correlation between the PAP content (as detected by IHC) and absolute radioactivity (% ID of 111In anti-PAP/g prostate). However, there was no correlation between radioactivity and the amount of cancer tissue (% of histological slices) inside the removed prostate tissue. In the pharmacokinetic studies, maximum activity in the serum was obtained within 3-5 hours after ipr injection; after that the kinetic behavior was similar to that after i.v. injection. After i.v. injection, two components could be distinguished the pharmacokinetic curves; the half-lives for mean distribution and elimination were 0.62 and 35.6 hours, respectively. The mean distribution half-life as well as the AUC from the pharmacokinetic curves correlated significantly with serum PAP (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo behavior of 111In-labeled monoclonal anti-prostatic acid phosphatase antibody after intraprostatic and intravenous injections. 763 61

Although Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in magnetic resonance imaging (MRI), it is known that contrast enhancement effect is not uniform if the concentration of Gd-DTPA increases beyond some levels. In this study, to evaluate the proper pulse sequences for dynamic MRI in the human kidney, the concentration of Gd-DTPA was quantitatively measured by inductively coupled plasma (ICP) emission spectrometry in human biological samples after administration of Gd-DTPA. The signal intensity of MRI in the solutions of several concentrations of Gd-DTPA was measured. The results were that in using a low magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 mumol/g under saturation recovery sequences (flip angle = 60 degrees or 90 degrees). Using a high magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 or 3.0 mumol/g under spin-echo or gradient-echo sequences. Gd-DTPA concentration of the renal cortex ranged from 0.132 to 0.152 mumol/g tissue at 5 min after IV injection of Gd-DTPA 0.05 mmol/kg body weight in six patients with adrenal tumor or renal cell cancer, and one patient with both urinary bladder cancer and prostatic cancer. Six of the patients showed normal renal function and the other had renal insufficiency (GFR = 25 ml/min/1.48 m2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does gadolinium-diethylene triamine pentaacetic acid enhanced MRI of kidney represent tissue concentration of contrast media in the kidney? In vivo and in vitro study. 800 71

Although Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in magnetic resonance imaging, it is known that contrast enhancement effect disappears if the concentration of Gd-DPTA increases beyond some levels. In this study, to evaluate the proper pulse sequences for dynamic magnetic resonance imaging (MRI) in the human kidney, the concentration of Gd-DTPA was quantitatively measured by inductively coupled plasma (ICP) emission spectrometry in human biological samples after administration of Gd-DTPA, and the signal intensity of MRI is the solutions of several concentrations of Gd-DTPA was measured. The results were; 1. In using a low magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 mumol/g under saturation recovery sequences (flip angle was 60 degrees or 90 degrees). Using a high magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 or 3.0 mumol/g under spin echo or gradient-echo sequences. 2. Gd-DTPA concentration of the renal cortex ranged from 0.132 to 0.152 mumol/g tissue at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight in 7 patients with adrenal tumor or renal cell cancer, and 1 patient with both urinary bladder cancer and prostatic cancer. Seven of them showed normal renal function and the other had renal insufficiency (GFR 25 ml/min/1.48 m2). Gd-DTPA concentrations of renal medulla and renal cell cancer tissue were 0.123 and 0.108 mumol/g tissue, respectively, at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight. These results suggest that the signal intensity of renal cortex, renal medulla, and renal cell cancer tissue may linearly correlate with Gd-DTPA concentration of tissues at 5 min after intravenous injection of Gd-DTPA 0.5 mmol/kg body weight.
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PMID:Concentration of gadolinium-diethylene triamine pentaacetic acid in human kidney--study on proper time for dynamic magnetic resonance imaging of the human kidney on low and high magnetic fields. 812 80

Purified human prostate acid phosphatase (PAP) was used to generate a specific monoclonal antibody (FC 3001) for detection of PAP expressed by some prostatic carcinomas. DTPA derivatives of MoAb-F(ab')2-fragments were labeled with indium-111 chloride. This labeled antibody was tested in 15 prostate cancer patients who underwent staging pelvic lymphadenectomy; 9 of them received labeled antibody alone whereas 6 received simultaneous injections of labeled and unlabeled antibody with two dose levels (40 or 80 mg). Biodistribution data obtained by direct blood measurements and imaging procedures indicated that simultaneous injection of unlabeled antibody reduced both the blood elimination rate and the accumulation in the liver. Accumulation of the radionuclide in pelvic lymph node metastases was observed in some patients but in a couple of patients accumulation was noted also in normal lymph nodes. The method cannot in its present design replace staging pelvic lymphadenectomy and further studies are needed for elaboration of clinically useful radioimmunodetection methods.
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PMID:Radioimmunodetection of prostate cancer by 111In-labeled monoclonal antibody against prostatic acid phosphatase. 830 18

Sandostatin, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with a commonly available, inexpensive radionuclide, 99mTc, and evaluated for its suitability for in vivo imaging. Labeling was accomplished by reduction of the cystine bridge, which provided two sulfhydryl groups for chelation with 99mTc. The complex was examined for thermodynamic stability in vitro and in experimental animals. Receptor specificity of the complex was determined using rat brain cortex membrane rich in somatostatin receptors, and its tissue distribution was studied in nude mice bearing human prostate cancer. In these studies, 99mTc-labeled oxytocin, a nonspecific peptide with similar molecular weight, served as a control and 111In-DTPA-octreotide served as a standard. The labeling method was simple, did not require protecting and deprotecting functional groups and yields were high (ca. 70%). The in vitro and in vivo stability was excellent, and Kd values were in the nanomolar range, similar to those of 111In-DTPA-octreotide. At 24 hours post-injection, the tumor uptake for 99mTc-Sandostatin, expressed as percent of injected dose per gram (% ID/g), was higher, but the tumor/blood and tumor/muscle ratios were lower than those for 111In-DTPA-octreotide. This agent, with its improved target-to-nontarget ratios, should prove to be of value for imaging somatostatin receptor-positive tumors.
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PMID:Sandostatin labeled with 99mTc: in vitro stability, in vivo validity and comparison with 111In-DTPA-octreotide. 887 94

To provide appropriate therapy for prostate cancer, accurate staging of the patient's disease is essential. Determination of tumor size, location, periprostatic extension and metastatic disease in the skeleton and soft tissue are needed to stage properly. Current diagnostic modalities may lead to understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both at the time of initial diagnosis and in patients with suspected local recurrence, can significantly alter the type of therapy given. Clinical studies using the (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab pendetide), have shown the superiority of radioimmunoscintigraphy over other diagnostic modalities in the detection of both primary and metastatic prostate cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of tumor-associated antigen rather than lesion size. Earlier detection of extraprostatic invasion and metastases by means of radioimmunoscintigraphy provides valuable information for treatment decisions. A case of metastatic prostate cancer in the abdomen of a patient without local disease, in which the extent of disease was confirmed at autopsy after sudden cardiac arrest, is presented.
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PMID:Prostate cancer abdominal metastases detected with indium-111 capromab pendetide. 954 74


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