Biomedical subjects

J C Reynolds

Publications and source records attributed to J C Reynolds.

At least 145 records · Page 8Linked to original sources

PubMed1988

Brownian dynamics simulation of protein association.

The Brownian Dynamics (BD) method is applied to study the diffusive dynamics and interaction of two proteins, cytochrome c (CYTC) and cytochrome c peroxidase (CYP). We examine the role of protein electrostatic charge distribution in the facilitation of protein-protein docking prior to the electron transfer step, assessing the influence of individual charged amino acid residues. Accurate interaction potentials are computed by iterating the linearized Poisson-Boltzmann (PB) equation around the larger protein CYP. The low dielectric constant inside proteins, electrolyte screening effects and irregular protein surface topography are taken into account. We observe a large ensemble of electrostatically stable encounter complexes seemingly with acceptable geometric requirements for electron transfer rather than a single dominant complex. Stabilities of the large variety of docking complexes are rationalized in terms of generalized charged residue complementarities. However, it is found that the electrostatic interactions giving rise to complex stabilities are somewhat nonspecific in nature. A large series of additional simulations are performed in which individual charged residues on CYTC have been chemically modified. Resulting perturbations of the association rate are significant and qualitatively similar to results observed in comparable kinetics experiments. We therefore demonstrate the potential of the Brownian dynamics method to estimate the effects of site-directed mutagenesis on protein-protein and protein-ligand diffusional association rates.

Amino Acids↗

PubMed1988

Barrett's esophagus in scleroderma: increased prevalence and radiographic findings.

Ten of 27 patients (37%) with scleroderma who underwent endoscopy at our hospital between 1980 and 1984 for symptoms of reflux esophagitis had biopsy-proven Barrett's esophagus. Two of those 10 patients had esophageal adenocarcinomas. In a blinded review of esophagrams (all but 2 using double-contrast technique) from 16 of the 27 patients, only 1 patient was thought to be at high risk for Barrett's esophagus due to a high esophageal stricture with an adjacent reticular pattern of the mucosa. The latter patient had biopsy-proven Barrett's mucosa. Eight patients were thought to be at moderate risk for Barrett's esophagus due to reflux esophagitis and/or distal strictures in 6 and polypoid intraluminal masses in 2. Three of the 6 patients with esophagitis and/or strictures had Barrett's esophagus, and both patients with masses had adenocarcinomas arising in Barrett's mucosa. Finally, 7 patients who had no esophagitis or strictures were thought to be at low risk for Barrett's esophagus. None of those 7 had histologic evidence of Barrett's mucosa. Thus, the major value of double-contrast esophagography is its ability to classify patients into high-, moderate-, and low-risk for Barrett's esophagus to determine the relative need for endoscopy and biopsy in these patients.

Adenocarcinoma↗

PubMed1988

Evidence for a direct and indirect action of leucine enkephalin at the feline ileocecal sphincter.

An in vitro whole organ bath preparation was used to examine the effects of leucine enkephalin on the cat ileocecal sphincter (ICS) intraluminal pressure and myoelectric activity. The bath allowed separation of the bathing media surrounding the ICS and the ileum. Leucine enkephalin (2 x 10(-7) M) when added to the ileal bathing medium caused a delayed increase in ICS spike activity and pressure which was blocked by tetrodotoxin (10(-5)M). In contrast, leucine enkephalin (2 x 10(-7)M) added directly to the ICS bathing medium caused an immediate spike-associated contractile response which was tetrodotoxin-resistant. Thus both an indirect and direct opiate action at the ICS was demonstrated.

Action Potentials↗

PubMed1988

Peritoneal carcinomatosis: imaging with intraperitoneal injection of I-131-labeled B72.3 monoclonal antibody.

Monoclonal antibody (MoAb) B72.3 is reactive with a variety of carcinomas such as colorectal and ovarian carcinoma and not reactive with a range of normal tissues in adults. Twelve patients, ranging in age from 16 to 63 years, with metastatic colorectal or appendiceal carcinoma were studied by means of radioimmunoscintigraphy after injection of 5-10 mCi (185-370 MBq) of iodine-131-labeled B72.3 immunoglobulin G (IgG). Eight of the 12 patients had positive scans. In three of these patients the MoAb scan depicted tumors that were not found by other means. Positive scans had excellent correlation with surgical findings in seven patients and caused underestimation of the extent of disease in one patient. In one patient the scan was technically inadequate and could not be evaluated. In three patients the scan was negative. No adverse reactions were associated with the infusions.

Adenocarcinoma↗

PubMed1988

Famotidine in the management of duodenal ulcer: an analysis of multicenter findings worldwide.

An integrated analysis of the fifteen published prospective multicenter studies that have examined the safety and efficacy of famotidine for the short-term (13) and maintenance (2) therapy of duodenal ulcer included over 2,600 patients. The thirteen studies of endoscopically proved acute duodenal ulcer that were published in English or were available in a complete English translation were reviewed. Six of these studies compared famotidine with ranitidine, one with cimetidine, one with gefarnate, and one with placebo, and four were uncontrolled. In controlled studies of the short-term therapy of symptomatic duodenal ulcer, famotidine was equal in efficacy to ranitidine or cimetidine and superior to placebo and gefarnate at all times examined. The efficacy of famotidine was examined in three oral dosing regimens--20 mg BID, 40 mg HS, and 40 mg BID. There were no significant differences in efficacy or side effects associated with these three regimens. Overall, the cumulative healing rate with famotidine was 46% at two weeks, 77% at four weeks, and 91% at eight weeks. In studies involving 50 patients or more, famotidine 40 mg orally HS resulted in healing rates for active duodenal ulcer of 82% to 100% after four weeks. Adverse effects were uncommon with all dosages examined. Adverse effects led to the discontinuation of therapy in three patients--two owing to the development of rash and one because of dizziness. Headache and constipation were the most common adverse experiences, but in no study were the adverse experiences that were seen with famotidine significantly more frequent than those seen with ranitidine or placebo. No patient undergoing therapy for active duodenal ulcer had a biochemical abnormality that required a change in therapy or that was drug related in the opinion of the investigator. Multicenter studies examining the efficacy of famotidine in reducing the incidence of duodenal ulcer recurrence showed that famotidine was superior to placebo at all intervals examined. In conclusion, the data from the studies included in this review show that famotidine is highly effective and generally well tolerated both in the short-term treatment of active duodenal ulcer and in the maintenance therapy of duodenal ulcer.

Drug Administration Schedule↗

PubMed1988

Correlation of mechanical properties of vertebral trabecular bone with equivalent mineral density as measured by computed tomography.

We tried to determine whether mineral-equivalent measurements that were obtained using computed tomography could be used to predict the mechanical properties of vertebral trabecular bone. Vertebral bodies that had been obtained during routine autopsy were evaluated by computed tomography. The mechanical properties of the vertebral trabecular bone were determined by subjecting cylindrical specimens to simple compression until failure occurred. The ultimate strength and elastic modulus were determined from load time curves, using constant displacement rate loading. Atomic absorption spectrophotometry was used to determine the weight per cent calcium of each specimen, and quantitative light microscopy was used to determine area fraction bone. Significant positive correlations were found between the observed mechanical properties of the trabecular bone and the equivalent mineral density as measured by computed tomography. Compressive strength (r = 0.720), elastic modulus (r = 0.574), trabecular calcium density (r = 0.780), and area fraction bone (r = 0.579) were all correlated with the equivalent mineral density.

Aged↗

PubMed1988

Effect of antibody dose on the imaging and biodistribution of indium-111 9.2.27 anti-melanoma monoclonal antibody.

Eleven patients with metastatic melanoma underwent serial gamma camera imaging and biodistribution measurements after i.v. injection of escalating doses of [111In]9.2.27, an antimelanoma murine monoclonal antibody. Patients received a fixed dose of 1 mg of [111In]9.2.27, with no additional 9.2.27 (five patients), or co-infused with 49 mg (five patients) or 99 mg (one patient) of unlabeled, unconjugated 9.2.27. Higher doses resulted in prolonged blood-pool retention, less uptake in spleen and bone marrow, and appeared to have a positive effect in improving tumor imaging. A dose of 1 mg of 9.2.27 permitted detection of tumors in two of five patients and two of ten lesions, while with greater than or equal to 50 mg, tumors were detected in all patients and in 24 of 32 lesions. Human gamma globulin injected prior to administration of [111In]9.2.27 failed to block the prominent liver, spleen, and bone marrow uptake. No toxicity was observed. These results indicate the feasibility of imaging metastatic melanoma with [111In]9.2.27 and suggest that antibody dose may be a critical determinant of biodistribution and tumor uptake.

Antibodies, Monoclonal↗

PubMed1988

Radioimmunoscintigraphy of colon cancer with iodine-131-labeled B72.3 monoclonal antibody.

The monoclonal antibody B72.3 is a murine IgG1 that is reactive with a wide range of carcinomas while demonstrating little or no reactivity to normal adult tissues. We have shown (27) quantitative analyses demonstrating selective targeting of [131I]B72.3 IgG to metastatic colorectal cancer. We have also shown (28) that (a) B72.3 localization in metastases correlated with the percentage of tumor cells in the biopsy specimen; (b) B72.3 could localize in carcinomas of various degrees of differentiation with best localization in well-differentiated tumors and (c) [131I]B72.3 could penetrate tumor masses, as determined by autoradiographic studies. We report here the various parameters effecting radioimmunoscintigraphy with [131I]B72.3 IgG. Sixteen of 35 patients with colorectal carcinoma had positive scans (without blood-pool subtraction). High circulating TAG-72 antigen levels correlated with positive scans. No dose dependent differences were seen in biodistribution or tumor imaging. The plasma clearance and urinary excretion of [131I]B72.3 and [125I]BL-3 (nonspecific control) were not significantly different. No toxicity was noted. Approximately one-half of patients developed human anti-mouse immune response.

Adolescent↗

PubMed1987

Immunolymphoscintigraphy and the dose dependence of 111In-labeled T101 monoclonal antibody in patients with cutaneous T-cell lymphoma.

Serial gamma camera imaging was performed in 11 patients with cutaneous T-cell lymphoma after s.c. injection between the toes of 111In-labeled T101, a pan T-cell monoclonal antibody. Two of the patients also received 111In-labeled 9.2.27, an isotype-matched control monoclonal antibody. Three doses of T101 (0.1, 0.5, and 1.0 mg), coupled with 0.5 mCi 111In, were used to measure lymph node uptake and dose response. A single 0.5-mg (0.5 mCi) dose of 111In-9.2.27 was used as control antibody to assess nonspecific uptake. Low-dose (0.1 mg) T101 administration produced rapid, intense uptake in inguinal-femoral and iliac nodes with minimal uptake in the paraaortic nodes and liver. The 0.5-mg dose and higher produced consistent uptake in all subdiaphragmatic nodes with greatest accumulation of liver activity at the 1.0-mg dose. In the two control studies, the ratio of specific:nonspecific antibody uptake in the inguinal-femoral, iliac, and paraaortic nodes averaged 7.7,5.9, and 1.9 at 48 h, respectively. In another patient, inguinal-femoral node biopsy contained over 2% of the injected dose of 111In-T101 per gram at 7 days. These findings suggest efficient and specific antibody binding in nodes nearest to the injection site, with progressive uptake of remaining antibody in more distant nodes as proximal sites approach saturation. Higher doses increase overflow of unbound antibody into the systemic circulation. There appears to be an optimal s.c. dose of approximately 0.5 mg (0.25 mg/foot) for T101 immunolymphoscintigraphy of subdiaphragmatic lymph nodes in patients with cutaneous T-cell lymphoma.

Adult↗

PubMed1987

Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72.3) in patients with carcinoma.

Monoclonal antibody (MAb) B72.3 has been shown to have selective reactivity for a wide range of carcinomas (colorectal, ovarian, breast, lung, gastric, and endometrial) versus normal adult tissues. 131I-Labeled B72.3 IgG has recently been shown to selectively bind carcinoma lesions when administered i.v. in patients with metastatic colorectal cancer. We report here the first direct comparison of i.p. administered [131I]B72.3 IgG to specifically localize metastatic carcinoma. Three of 10 patients studied were negative for tumor detection by both CAT scan and X-ray but were positive for tumor localization via gamma scanning i.p. administered 131I-labeled MAb B72.3 IgG. Direct analyses of biopsy specimens of carcinoma and normal tissues demonstrated ratios of greater than 70:1 (based on percentage of injected dose/mg) for tumor MAb localization versus normal tissues. Specificity of [131I]B72.3 tumor targeting was demonstrated by the concomitant administration of an equal dose of an 125I-labeled isotype identical (IgG1) control MAb. Simultaneous i.p. administration of [131I]B72.3, and i.v. administration of [125I]B72.3 in individual patients demonstrated: peritoneal implants are targeted more efficiently via i.p. MAb administration, and hematogenously spread and lymph node metastases as well as local recurrences are targeted more efficiently by i.v. administered MAb. No antibody toxicity was observed in any patients. Pharmacokinetics of MAb clearance demonstrated that only 10 to 30% of the i.p. administered MAb was found in plasma. These studies thus demonstrate the efficacy of intracavitary MAb administration as well as the advantage of the concomitant use of intracavitary and i.v. administered MAbs for tumor targeting and for potential MAb guided therapy of metastatic carcinoma.

Adolescent↗

PubMed1987

Kinetic model for the biodistribution of an 111In-labeled monoclonal antibody in humans.

Using data from 12 patients, we have analyzed the pharmacokinetics of 111In-9.2.27, an antimelanoma monoclonal antibody, following i.v. infusion. Plasma data and scintillation camera images obtained from patients receiving either 1, 50, or 100 mg of monoclonal antibody indicated dose-dependent (i.e., saturable) kinetics. Based on these observations and known immunoglobulin kinetics, we developed a nonlinear compartmental model to describe the biodistribution of 111In-9.2.27 and the other coinjected 111In-associated compounds. The model included (a) three compartments representing intact 111In-9.2.27 ("plasma," "nonsaturable," and "saturable binding" compartments), (b) four compartments representing 111In-diethylenetriaminepentaacetic acid, and (c) one compartment representing 111In in an undetermined chemical form ("extravascular delay" compartment). Analysis of the rate of urinary excretion relative to plasma concentration indicated that the saturable binding compartment was a site for catabolism of monoclonal antibody. Further examination of the urinary data, together with previous studies of the site(s) of immunoglobulin catabolism, suggested that additional elimination took place from either the plasma or the nonsaturable compartment. The model indicated that to fill the saturable sites would require a dose of approximately 0.5 mg and suggested that greater than 3.5 mg would maintain saturation for 200 h. Computer integration of gamma camera counts over the spleen revealed a clear saturable component of uptake, whereas integration over the liver showed no such pattern. The proposed model was fitted to the liver and spleen imaging data by summing fractions of model simulations of each compartment. That analysis confirmed the suspected saturable uptake by the spleen (21% of the saturable binding compartment) and revealed a quantitatively important component of saturation in the liver (35% of the saturable binding compartment) that was not obvious from initial examination of the images. When the results were expressed on a concentration basis, the spleen accounted for 247% of the saturable compartment per kg, whereas the liver accounted for 25%/kg. The bone marrow also showed saturable uptake; hence, the saturable uptake may relate to the sinusoidal blood supply characteristic of liver, spleen, and marrow. The model predicts the dose levels required to overcome saturable background, suggests appropriate doses and schedules for cold loading strategies, and provides a format for explicit inclusion of tumor antigen.

Antibodies, Monoclonal↗

PubMed1987

Quantitative analyses of selective radiolabeled monoclonal antibody localization in metastatic lesions of colorectal cancer patients.

We have previously demonstrated, using in vitro assays, a high degree of selective binding of monoclonal antibody (MAb) B72.3 for carcinomas of the colon, ovary, and breast versus normal adult tissues using in vitro assays. We report here a demonstration of selective tumor localization in colorectal cancer patients of i.v. administered 131I-labeled MAb B72.3 immunoglobulin G prior to surgery. Radiolocalization indices (RI) were obtained by direct analyses of biopsy materials (i.e., cpm of 131I-labeled MAb per g of tumor versus cpm per g of normal tissues). Using as a "positive" localization, RI of 3 times greater than normal tissue (i.e., RI greater than 3.0), tumor lesions in various sites from 17 of 20 patients scored positive. In eight of these patients, all tumor lesions demonstrated RIs of greater than 3, while in five patients RIs of some lesions were greater than 10 and as high as 30 to 46. Seventy % (99 of 142) of tumor lesions showed RIs of greater than 3, while only 12 of 210 histologically confirmed normal tissues examined showed RIs of greater than 3. These tissues, moreover, were either adjacent to tumor or draining tumor masses, or, as in the case of two patients, apparently due to high levels of circulating immune complexes that were deposited in the spleen. Positive gamma scans (confirmed at surgery) were observed in 14 of 27 patients. An isotype-identical control immunoglobulin G was coinjected and showed RIs considerably lower than that of B72.3. No toxicity or adverse reaction was observed with either MAb. These studies are among the most comprehensive to date concerning the definition of the actual delivery of radiolabeled MAb to carcinoma lesions versus a wide range of adjacent and distal normal tissues and lead the way for other diagnostic and potential therapeutic applications of this antibody either alone, or in combinations with other monoclonal antibodies.

Antibodies, Monoclonal↗

PubMed1987

Quantitative and qualitative aspects of radiolocalization in colon cancer patients of intravenously administered MAb B72.3.

Monoclonal antibody (MAb) B72.3 has been previously shown, by in vitro assays, to have a high degree of specificity for carcinomas of the colon, ovary and breast versus normal adult tissues. B72.3 IgG was labelled with 131I and injected i.v. into 20 patients with known or suspected colorectal cancer. All patients subsequently underwent surgical exploration, with tumor and selected normal tissues removed for staging purposes. The selective localization of 131I-MAb B72.3 IgG was demonstrated in biodistribution studies in which the % ID/g of each tumor was compared with that of the normal tissues, thus providing a relative RI for each lesion. Of the tumor lesions, 70% (99/142) had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues), and 31% of the tumor lesions had RIs of over 10. Only 12 of 210 (6%) histologically normal tissues had RIs of greater than 3; either these tissues were adjacent to or draining tumor masses or, as in the case of 2 patients, the high RI values were apparently due to deposition of immune complexes in the splenic tissues. Several parameters were studied to determine factors that might influence MAb localization. Whereas tumors of all histologic types localized the MAb, 31% of the well-differentiated mucinous carcinomas displayed tumor-to-normal ratios greater than 10, while less than 5% of the lesions of other tumor types demonstrated similar localization. The expression of the antigen (TAG-72) detected by MAb B72.3 in these tumors, as studied by immunohistochemical techniques using tissue sections, did not always correlate with the outcome of the MAb distribution. No differences in MAb uptake were observed among the carcinoma lesions from numerous anatomic locations, demonstrating the ability of i.v. administered B72.3 to reach all the tumor sites. Furthermore, autoradiographic studies of tumors showed good penetration of the MAb into the medial areas of the tumors, regardless of their size.

Adolescent↗

PubMed1987

Esophageal chest pain. Value of high-dose provocative testing with edrophonium chloride in patients with normal esophageal manometries.

The unequivocal diagnosis of esophageal chest pain requires the demonstration of simultaneous manometric changes and chest pain. Numerous provocative agents have been used to enhance the diagnostic value of esophageal manometry. Our aims were to: evaluate consecutively a large group of patients with proven noncardiac chest pain and normal baseline manometric studies, using edrophonium chloride, 10 mg, and determine the value of provocative testing in clinical practice. One hundred twenty patients with normal standard baseline esophageal manometries were studied using blinded testing with edrophonium chloride and followed clinically by questionnaire. A positive response of both chest pain and manometric changes was observed in 34%, a negative response in 49%, and an indeterminate response in 17% of patients. Baseline manometric features, including high-amplitude contractions, did not predict the response to edrophonium chloride. Following edrophonium chloride administration, the change in amplitude, duration, and number of repetitive contractions from baseline was significantly greater in positive responders. Edrophonium decreased the velocity of propagated contractions in positive responders (P less than 0.05), but not in nonresponders. Response to edrophonium chloride could not be predicted by patient age, sex, or clinical symptomatology. Seventy percent of patients in both groups had symptoms indistinguishable from ischemic heart disease. After making a specific diagnosis of esophageal chest pain, patients showed a marked clinical improvement, with a significant decrease in physical limitation, emergency room visits, hospital and CCU admissions, and in further cardiac testing. We conclude that provocative testing with edrophonium chloride will make it possible to definitively implicate the esophagus in over 30% of patients with normal baseline manometric findings and noncardiac chest pain.

Adult↗

PubMed1987

Barrett's metaplasia and adenocarcinoma of the esophagus in scleroderma.

Gastroesophageal reflux is well documented in scleroderma, but the complications of Barrett's metaplasia and adenocarcinoma are not well described. The records of 75 patients with scleroderma seen over a four-year period at the Hospital of the University of Pennsylvania were retrospectively reviewed to determine the prevalence of Barrett's metaplasia and adenocarcinoma of the esophagus and to identify clinical, manometric, laboratory, or radiographic criteria that might predict the presence of these lesions. Twenty-four of these patients underwent endoscopy. In this group, the prevalence of Barrett's metaplasia was 37 percent (nine patients) and adenocarcinoma was also present in two of these patients. The patients with and without Barrett's metaplasia were similar in age (range, 22 to 64 compared with 28 to 79, respectively), sex (six of nine compared with 12 of 15 female, respectively), frequency of esophageal motility disorders, presence of proximal skin involvement, digital ulceration, and pulmonary involvement as measured by diffusion capacity. Barrett's metaplasia was diagnosed on the basis of double-contrast esophagographic results in only one of eight patients with Barrett's metaplasia so-studied. Patients with Barrett's metaplasia tended to have longer duration of heartburn (90 +/- 40 months compared with 11 +/- 35 months) and dysphagia (39 +/- 22 months compared with 7 +/- 3 months). Patients with Barrett's metaplasia also tended to have greater impairment of lower esophageal sphincter pressure either at end-expiration (4.0 +/- 2.1 compared with 6.1 +/- 1.8 mm Hg) or mid-respiration (13.0 +/- 3.0 compared with 16.9 +/- 2.5 mm Hg). Using chi-square analysis, however, none of these differences reached statistical significance. Discrimination did occur on the basis of the presence of the CREST (calcinosis, Raynaud's phenomenon, esophageal manifestations of scleroderma, sclerodactyly, and telangiectasis) variant (55 percent compared with 7 percent, p less than 0.01), a duration of dysphagia of more than five months (p less than 0.03), and mid-respiratory lower esophageal sphincter pressure of less than 10 mm Hg (p less than 0.05). It is suggested that: Barrett's metaplasia of the esophagus occurs in one third of patients with scleroderma; clinical, manometric, laboratory, and radiographic features are poor predictors of the presence of Barrett's metaplasia; patients with CREST syndrome, prolonged dysphagia, or a very low lower esophageal sphincter pressure may have an increased risk for the development of metaplasia; patients with scleroderma and Barrett's metaplasia have an increased risk of complications such as stricture or adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMed1987

Properties of the feline pyloric sphincter in vitro.

The purpose of this study was to determine the intrinsic functions of the feline pylorus in vitro. The myoelectric and pressure characteristics of the intact pylorus, antrum, and duodenum, free of extrinsic hormonal or neural influences, were studied in an in vitro bath that allowed separation of the bathing medium surrounding the different bowel segments. Basal recordings revealed a zone of tonic high pressure of 28.4 +/- 3.5 mmHg (mean +/- SEM) at the pylorus. The basal slow wave frequencies in the pylorus and duodenum were 2.8 +/- 1.4 and 12.6 +/- 0.6 cycles/min, respectively. Spontaneous action potential-associated phasic contractions of the pylorus were noted in 38% of preparations. Enteric nerve stimulation with direct electric current (10 Hz, 1 ms, 10-50 V) applied proximal to the pylorus gave relaxation of the pylorus at the lower voltages and rebound excitation at higher voltages. Electrical stimulation distal to the pylorus yielded phasic contractile pyloric response during the entire stimulus. The duodenal instillation of 0.5 N HCl produced action potential-associated phasic contractions of the pylorus and duodenum but not the antrum. Pyloric responses to electrical stimulation or acidification were abolished by tetrodotoxin (10(-5) M). Bethanechol (10(-6) M) or substance P (10(-7) M) produced a contractile response at the site of stimulation but this response was not transmitted to include adjacent bowel segments. These studies suggest that the pyloric sphincter with its intrinsic reflex properties can be studied in vitro.

Action Potentials↗

PubMed1987

Radiolabeled monoclonal antibody B72.3 localization in metastatic lesions of colorectal cancer patients.

We have previously demonstrated a high degree of selective binding of monoclonal antibody (MAb) B72.3 to carcinomas of the colon, ovary, and breast in contrast to normal adult tissues using in vitro assays. In this report we demonstrate selective tumor localization in colorectal cancer patients after intravenously administering 131I-labeled MAb B72.3 IgG. Radiolocalization Indices (RI) (i.e. cpm 131I-labeled MAb per gram of tumor vs cpm per gram of normal tissues), were obtained by direct analyses of biopsy materials. Using an RI of greater than or equal to 3 as a positive localization, tumor lesions in various sites from 17/20 patients scored positive. In eight of these patients, all tumor lesions demonstrated RIs of greater than 3, while in five patients RIs of some lesions were greater than 10 and as high as 30-46. Seventy percent (99/142) of the tumor lesions showed RIs of greater than 3, while only 12 of 210 histologically confirmed normal tissues examined showed RIs of greater than 3. These tissues were either adjacent to the tumor or the draining tumor masses or, as in the case of two patients, was caused by high levels of circulating immune complexes that deposited in the spleen. Positive scintigraphic images (confirmed at surgery) were observed in 14/27 patients. No toxicity or adverse reactions were observed with either MAb. These studies provide absolute quantitative analyses of the actual delivery of radiolabeled MAb to carcinoma lesions vs a wide range of adjacent and distal normal tissues and establishes the means for other diagnostic and potential therapeutic applications of this antibody alone, or in combinations with other monoclonal antibodies.

Antibodies, Monoclonal↗

PubMed1987

Indium-111 T101 monoclonal antibody is superior to iodine-131 T101 in imaging of cutaneous T-cell lymphoma.

We have reported that [111In]T101 is highly effective in the detection of cutaneous T-cell lymphoma (CTCL) in nodal and cutaneous (erythroderma and tumor) sites. This study compares the biodistribution of [131I]T101 (1 to 7.1 mg, 2 mCi) in four patients with CTCL; two of these patients also received [111In]T101 (1 mg, 5 mCi). There was rapid clearance of [131I]T101 from whole-body, spleen, liver, and bone marrow, with evidence of loss of 131I tracer from the T101. Lymph node uptake was minimal in three of four patients, and there was no localization in skin lesions. This contrasted with [111In]T101 where there was prolonged retention of activity in these organs and excellent uptake in skin tumors, erythroderma, and lymph nodes. The study showed that [131I]T101 was suboptimal for imaging CTCL patients and demonstrates that the isotope or labeling method can dramatically alter the apparent biodistribution and tumor targeting of a given monoclonal antibody.

Animals↗