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Biomedical subjects

A M Scott

Publications and source records attributed to A M Scott.

At least 55 records · Page 3Linked to original sources
PubMed1999

Positron emission tomography: radioisotope and radiopharmaceutical production.

A Centre for Positron Emission Tomography (PET) has been operational within the Department of Nuclear Medicine at the Austin & Repatriation Medical Centre (A&RMC) in Melbourne for seven years. PET is a non-invasive imaging technique based on the use of biologically relevant compounds labelled with short-lived positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. The basic facility consists of a medical cyclotron (10 MeV proton & 5 MeV deuteron), six lead-shielded hotcells with associated radiochemistry facilities, radiopharmacy and a whole body PET scanner. A strong radiolabelling development program, including the production of 15O-oxygen, 15O-carbon monoxide, 15O-carbon dioxide, 15O-water, 13N-ammonia, 18F-FDG, 18F-FMISO, 11C-SCH23390 and 11C-flumazenil has been pursued to support an ambitious clinical and research program in neurology, oncology, cardiology and psychiatry.

Drug Design↗
PubMed1998

The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic imaging to radiotherapy planning in lung cancer.

A retrospective analysis was performed to determine whether coronal thoracic [18F]fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) scans, if viewed at the time of radiotherapy (RT) planning, would have influenced the anterior-posterior (AP) RT volumes that were administered to a group of unoperated lung cancer patients. Viewing of PET and diagnostic images enabled a qualitative assessment of whether abnormal thoracic PET activity was present in areas regarded as normal by diagnostic imaging; this would, therefore, have influenced the RT volume if done prospectively. Additionally a method of graphical co-registration was devised to quantitate the adequacy of coverage of each patient's abnormal PET activity by his/her actual RT field. Of 15 patients analyzed, 26.7% (four patients) would have had their RT volume influenced by PET findings, highlighting the potential value of PET in treatment planning.

Fluorine Radioisotopes↗
PubMed1998

Direct immobilization of gangliosides onto gold-carboxymethyldextran sensor surfaces by hydrophobic interaction: applications to antibody characterization.

We describe a novel immobilization technique to investigate interactions between immobilized gangliosides (GD3, GM1, and GM2) and their respective antibodies, antibody fragments, or binding partners using an optical biosensor. Immobilization was performed by direct injection onto a carboxymethyldextran sensor chip and did not require derivatization of the sensor surface or the ganglioside. The ganglioside appeared to bind to the sensor surface by hydrophobic interaction, leaving the carbohydrate epitope available for antibody or, in the case of GM1, cholera toxin binding. The carboxyl group of the dextran chains on the sensor surface did not appear to be involved in the immobilization as evidenced by equivalent levels of immobilization following conversion of the carboxyl groups into acyl amino esters, but rather the dextran layer provided a hydrophilic coverage of the sensor chip which was essential to prevent nonspecific binding. This technique gave better reactivity and specificity for anti-ganglioside monoclonal antibodies (anti-GD3: KM871, KM641, R24; and anti-GM2: KM966) than immobilization by hydrophobic interaction onto a gold sensor surface or photoactivated cross-linking onto carboxymethydextran. This rapid immobilization procedure has facilitated detailed kinetic analysis of ganglioside/antibody interactions, with the surface remaining viable for a large number of cycles (>125). Kinetic constants were determined from the biosensor data using linear regression, nonlinear least squares and equilibrium analysis. The values of kd, ka, and KAobtained by nonlinear analysis (KAKM871 = 1.05, KM641 = 1.66, R24 = 0.14, and KM966 = 0.65 x 10(7) M-1) were essentially independent of concentration and showed good agreement with data obtained by other analytical methods.

Antibodies, Monoclonal↗
PubMed1998

Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole.

OBJECTIVE: To show that PET with 18F-fluoromisonidazole (18F-FMISO) can detect peri-infarct hypoxic tissue in patients after ischemic stroke. BACKGROUND: PET with (15)O-labeled oxygen and water is the only established method for identifying the ischemic penumbra in humans. We used PET with 18F-FMISO in patients after ischemic stroke to identify hypoxic but viable peri-infarct tissue likely to represent the ischemic penumbra, and to determine how long hypoxic tissues persist after stroke. METHODS: Patients with acute hemispheric ischemic stroke were studied using PET with 18F-FMISO either within 48 hours or 6 to 11 days after stroke onset. The final infarct was defined by CT performed 6 to 11 days after stroke. Tracer uptake was assessed objectively by calculating the mean activity in the contralateral (normal) hemisphere, then identifying pixels with activity greater than 3 SDs above the mean in both hemispheres. Positive studies were those with high-activity pixels ipsilateral to the infarct. RESULTS: Fifteen patients were studied; 13 within 48 hours of stroke, 8 at 6 to 11 days, and 6 during both time periods. Hypoxic tissue was detected in 9 of the 13 patients studied within 48 hours of stroke, generally distributed in the peripheries of the infarct and adjacent peri-infarct tissues. None of the 8 patients studied 6 to 11 days after stroke exhibited increased 18F-FMISO activity. All 6 patients studied both early and late exhibited areas of increased activity during the early but not the late study. CONCLUSIONS: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).

Acute Disease↗
PubMed1998

Rapid and specific targeting of monoclonal antibody A33 to a colon cancer xenograft in nude mice.

Monoclonal antibody (mAb) A33 detects a glycoprotein homogeneously expressed by > 95% of human colon cancers and by normal colon cells. The A33 antigen is not secreted or shed and after mAb A33 binds to antigen on the cell membrane, a fraction of membrane-bound mAb A33 is internalized into endosomes. Phase I 131I-mAb A33 biodistribution studies have shown consistent, specific tumor-targeting, and phase I radioimmunotherapy trials with 131I- or 125I-mAb A33 have demonstrated antitumor effects. Here we describe a nude mouse model that was established using a human colon cancer cell line, SW1222, which grows as a relatively hypovascular, invasive heterotransplant when injected i.m. Peak uptake of 131I-labeled or 111In-chelated mAb A33 was observed at 48-96 h, with a mean of 34% (SE +/- 5.0) and 46.7% (SE +/- 1.7) injected dose per gram of tumor tissue, respectively. 111In-mAb A33 was retained in tumor tissue longer than halide radioimmunoconjugates. The specificity of antibody localization was assessed using a control antibody (tumor uptake and pharmacokinetics), a control tumor, corrections for vascular antibody blood-pooling in tumor tissue, and blocking of radiolabeled mAb A33 localization by pretreating mice with excess unlabeled mAb A33. These experiments demonstrate that mAb A33 localization in tumor was specific, and they emphasize the unexpected rapidity with which the antibody localizes. Our conclusions were confirmed by immunohistochemical techniques which allowed direct visualization of localization and distribution of the humanized version of mAb A33 in tumor tissue. Furthermore, antibody doses approximating tumor-saturating doses demonstrated that a homogeneous distribution of antibody in tumor is possible. This model will be valuable for studies focusing on general physiologic aspects of antibody-to-tumor cell localization and critical as a guide to the evaluation of various A33 antibody constructs and combinations with other therapies for the treatment of colon cancer.

Animals↗
PubMed1998

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma.

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.

Adult↗
PubMed1997

Kinetic analysis of the interaction between the monoclonal antibody A33 and its colonic epithelial antigen by the use of an optical biosensor. A comparison of immobilisation strategies.

The interaction between the humanised A33 monoclonal antibody and the corresponding F(ab)'2 or Fab' fragments with the colonic epithelial A33 antigen, purified by micropreparative HPLC from membrane extracts of the colonic carcinoma cell line LIM 1215, has been studied with the BIAcore 2000 biosensor using surface plasmon resonance detection. The surface orientation of immobilised antibody and the Fab' fragment onto the biosensor surface was controlled using alternative immobilisation chemistries. This resulted in significantly higher molar binding activities compared with the conventional N-hydroxysuccinimide (NHS)/N-ethyl-N'-dimethylaminopropylcarbodiimide (EDC) chemistry. This increase in signal resulted in a concomitant increase in sensitivity of detection, which facilitates analysis of low levels of A33 antigen. The apparent association rate (ka) and dissociation rate (kd) constants obtained with the different immobilisation chemistries were determined. These analyses showed that the kinetic constants obtained for the IgG were not significantly affected by the method of immobilisation. F(ab)'2 and Fab' fragments immobilised using NHS/EDC chemistry showed significantly lower apparent affinity. By contrast the use of the thiol coupling chemistry with the Fab' fragment gave a five fold increase in observed KA, resulting in a similar affinity to that observed with the intact IgG molecule.

Antibodies, Monoclonal↗
PubMed1997

The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily.

The mAb A33 detects a membrane antigen that is expressed in normal human colonic and small bowel epithelium and > 95% of human colon cancers. It is absent from most other human tissues and tumor types. The murine A33 mAb has been shown to target colon cancer in clinical trials, and the therapeutic potential of a humanized antibody is currently being evaluated. Using detergent extracts of the human colon carcinoma cell lines LIM1215 and SW1222, in which the antigen is highly expressed, the molecule was purified, yielding a 43-kDa protein. The N-terminal sequence was determined and further internal peptide sequence obtained following enzymatic cleavage. Degenerate primers were used in PCRs to produce a probe to screen a LIM1215 cDNA library, yielding clones that enabled us to deduce the complete amino acid sequence of the A33 antigen and express the protein. The available data bases have been searched and reveal no overall sequence similarities with known proteins. Based on a hydrophilicity plot, the A33 protein has three distinct structural domains: an extracellular region of 213 amino acids (which, by sequence alignment of conserved residues, contains two putative immunoglobulin-like domains), a single hydrophobic transmembrane domain, and a highly polar intracellular tail containing four consecutive cysteine residues. These data indicate that the A33 antigen is a novel cell surface receptor or cell adhesion molecule in the immunoglobulin superfamily.

Amino Acid Sequence↗
PubMed1997

Pneumocystis carinii pneumonia postrestorative proctocolectomy for ulcerative colitis: a role for perioperative prophylaxis in the cyclosporine era? Report of a case and review of the literature.

PURPOSE: Medical management of severe ulcerative colitis has used cyclosporine with increasing frequency as an adjuvant to systemic steroids and mercaptopurine. However, the effects of combined management with cyclosporine and prednisone may lead to significant immune compromise and adversely affect operative morbidity in the event urgent surgery is required. METHODS: A case is reported of a 43-year-old white male who presented with severe ulcerative colitis. The patient had been initially treated with prednisone and cyclosporine for six weeks before surgical intervention. The intractability of his ulcerative colitis caused the patient to present to surgery, where he underwent restorative proctocolectomy. RESULTS: On initial presentation, the patient manifested systemic signs of severe ulcerative colitis with hypoalbuminemia, anemia, and weight loss, despite continuous prednisone and cyclosporine management. Before surgical intervention, a chest x-ray and the patient's respiratory status were normal. A total abdominal colectomy with ileal pouch reconstruction and temporary loop ileostomy were performed without incident. On the fifth postoperative day, the patient developed respiratory failure, which was subsequently diagnosed as Pneumocystis carinii pneumonia. Although ventilator support and both aggressive medical and surgical management eventually resulted in successful outcome, significant perioperative morbidity occurred. CONCLUSIONS: In the era of aggressive medical management for ulcerative colitis with both steroids and cyclosporine, the complications of immunosuppression may be significant, including opportunistic pneumonia. Prophylaxis against P. carinii pneumonia with sulfa antibiotics should be considered, especially in patients for whom proctocolectomy is a potential end point.

Adult↗
PubMed1997

Antibody-based immunological therapies.

Clinical research in the area of antibody-based tumor-targeted therapy has been driven for many years by the prospect of identifying cell surface antigens with sufficient restrictive tissue expression patterns to allow for the selective and specific accumulation of antibody in tumor tissue. Few, if any, such antibody-antigen systems have been identified which can effectively deliver a large fraction of an administered therapeutic agent to metastatic cancer. Despite this limitation, however, a greater understanding of the biological and physiological principles of tumor-targeted therapy has resulted in successful antibody-based therapy of lymphoma, colon cancer and breast cancer in recent clinical trials.

Antibodies, Neoplasm↗
PubMed1997

Resuscitation from hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, or hetastarch.

BACKGROUND: An oxygen-transporting hemoglobin solution should be more effective than a nonhemoglobin solution for resuscitation from hemorrhagic shock. A way to evaluate this effectiveness is to determine whether a hemoglobin solution can reverse the base deficit accumulated during hemorrhage at a faster rate than a nonhemoglobin solution. Using this criterion, we compared the resuscitative powers of autologous blood, hetastarch (Het), and diaspirin cross-linked hemoglobin (DCLHb). METHODS: Fifteen sedated, spontaneously breathing sheep (37.5 +/- 10.2 kg) were bled until base deficits fell to -5 to -10 mEq/L, and plasma lactate concentrations rose to 6 to 9 mg/L. The animals were resuscitated with autologous blood (n = 5), Het (n = 5), or DCLHb (n = 5) (3.5-4.0 mL/kg every 15 minutes) until base deficits returned to prehemorrhage baseline. RESULTS: Exsanguination to target base deficits required removal of an average of 41.4 +/- 5.5 mL blood/kg (estimated total blood volume, 80 mL/kg). Resuscitation required 18 +/- 3, 38 +/- 2 (different from blood), and 35 +/- 1 (different from blood) mL/kg of autologous blood, Het and DCLHb, respectively, over periods of 78 +/- 8, 163 +/- 10 (different from blood), and 129 +/- 9 minutes (different from blood and different from Het (p < or = 0.05)). Based on regression analysis, autologous blood, Het, and DCLHb corrected the base deficit at rates of, respectively, 0.074 (different from Het (p < or = 0.05)), 0.016, and 0.056 (different from Het (P < or = 0.05)) mEq/L/min. CONCLUSIONS: Based on the rate of base deficit correction and the volume of solution required, autologous blood was the most effective resuscitation solution. However, DCLHb was more effective than Het. DCLHb may be an attractive alternative to blood for resuscitation from hemorrhagic shock.

Animals↗
PubMed1997

Implementation and evaluation of patient-specific three-dimensional internal dosimetry.

UNLABELLED: Current methods for calculating the absorbed dose in a target region from a source region rely on a standard "reference man" geometry and assume an uniform distribution of radiolabel. While this approach is acceptable at the low levels of radioisotope administered for most diagnostic purposes, the generality of the calculations is not adequate for doses at the higher levels required for therapy and is not easily extendible to tumor dosimetry. METHODS: We have developed an integrated system which utilizes patient anatomy and radionuclide distribution in the calculation of absorbed dose rate or total dose to any user-defined target region. Images of radionuclide distribution (PET/SPECT) are registered to anatomic images (CT/ MRI) and then entered into a three-dimensional internal dosimetry software system (3D-ID) where regions of interest are defined. Dose calculations are performed by the mathematical convolution between a user-specified, dose-point kernel with the activity in the source volume over the target volume. The resulting dose rate distribution may be scaled by cumulated activity to yield absorbed dose. In addition to calculating the mean dose, dose-volume histograms may be generated which plot absorbed dose with respect to percent of volume. The method was evaluated using selected standard man phantom organs. RESULTS: Dose estimates for two patient studies are included to illustrate differences between patient-specific and MIRD-based calculations. The package provides an alternative approach to image display and three-dimensional internal dose calculations. CONCLUSION: The dose-volume histogram representation of absorbed dose to a target volume provides valuable information in assessing tumor control probability and normal tissue toxicity.

Dose-Response Relationship, Radiation↗
PubMed1996

Purification and characterization of a novel restricted antigen expressed by normal and transformed human colonic epithelium.

A cell surface antigen that is expressed by normal and 95% of transformed colonic epithelium and is recognized by the monoclonal antibody A33 (Welt, S., Divgi, C. R., Real, F. X., Yeh, S. D., Garin-Chesa, P., Finstad, C. L., Sakamoto, J., Cohen, A., Sigurdson, E. R., Kemeny, N., Carswell, E. A., Oettgen, H. F., and Old, L. J. (1990) J. Clin. Oncol. 8, 1894-1906) has been purified to homogeneity from the human colonic carcinoma cell line LIM1215. The A33 protein was purified from Triton X-114 extracts of LIM1215 cells under nondenaturing conditions. These extracts were applied sequentially to Green-Sepharose HE-4BD, Mono-Q HR 10/10, Superose 12 HR 10/30, and micropreparative Brownlee Aquapore RP 300. The purification was monitored by biosensor analysis using surface plasmon resonance detection with a F(ab')2 fragment of the humanized A33 monoclonal antibody immobilized on the sensor surface and Western blot analysis following SDS-polyacrylamide gel electrophoresis (PAGE) under nonreducing conditions using humanized A33 monoclonal antibody. The purified A33 antigen has a Mr on SDS-PAGE of 43,000 under nonreducing conditions. By contrast, the purified protein displayed a Mr of approximately 180,000 under native conditions on both size exclusion chromatography and native PAGE, possibly due to the formation of a homotetramer. N-terminal amino acid sequence analysis of the purified protein identified 34 amino acid residues of a unique sequence: ISVETPQDVLRASQGKSVTLPXTYHTSXXXREGLIQWD. A polyclonal antibody was raised against a synthetic peptide corresponding to residues 2-20 of this sequence. The antipeptide serum recognized the purified protein using Western blot analysis under both nonreducing (Mr 43,000) and reducing (Mr 49,000) conditions.

Amino Acid Sequence↗
PubMed1996

Thoracic versus lumbar epidural anesthesia's effect on pain control and ileus resolution after restorative proctocolectomy.

BACKGROUND: Epidural anesthesia as a perioperative adjunct has been shown to provide superior pain control and has been implicated in more rapid ileus resolution after major abdominal surgery, possibly through a sympatholytic mechanism. Studies suggest that the vertebral level of epidural administration influences these parameters. METHODS: One hundred seventy-nine patients (120 male, 59 female; average age, 36 years) underwent restorative proctocolectomy for ulcerative colitis or familial polyposis between 1989 and 1995. Patients were grouped according to type of anesthesia. Group THO (n = 53) received thoracic (T6 to T10) epidurals. Group LUM (n = 51) received lumbar (L2 to L4) epidurals, and group PCA (n = 75) received patient-controlled intravenous narcotic analgesia. Patients were compared for complications, perioperative risk factors, postoperative pain, and ileus resolution. RESULTS: Epidural narcotics, alone or combined with local anesthetics, were administered for an average of 2 (LUM) to 4 (THO) days without significant complications. Infrequent problems related to the epidural catheters included self-limited headaches or back pain (four) and site infections (two). Epidural failure, as measured by conversion to PCA for inadequate pain control, was not significantly greater for LUM (25%) than THO (23%). Average pain scores, rated daily on a visual analog scale, were significantly higher (indicating more pain) for PCA patients (4.2) during postoperative days 1 through 5 than for LUM (3.5) (p < 0.05) and for THO (2.4) (p < 0.05). Ileus resolution, as determined by stool output and return of bowel sounds, was significantly faster in THO than in LUM or PCA (p < 0.05). Resolution of ileus was not significantly different between PCA and LUM (p > 0.05). CONCLUSIONS: Thoracic epidural analgesia has distinct advantages over both lumbar epidural or traditional patient-controlled analgesia in shortening parameters measuring postoperative ileus and in reducing surgical pain. The procedure is safe and associated with low morbidity. Thoracic epidural anesthesia is also economically justifiable and may prove to impact significantly on future postoperative management by reducing length of hospitalization. Our data and those of others are most striking in these regards for patients with thoracic catheters, indicating the importance of vertebral level in epidural drug administration.

Adolescent↗
PubMed1996

Comparison of optimised planar scintigraphy with SPECT thallium, exercise ECG and angiography in the detection of coronary artery disease.

BACKGROUND: Thallium SPECT has been shown to be more sensitive than planar imaging in the detection of coronary heart disease (CAD) in a number of reported series. Early (< 10 minutes) redistribution on planar imaging has been demonstrated in clinical studies and this may partly contribute to its lower sensitivity. AIM: To determine whether thallium SPECT is superior to planar scintigraphy (with the timing of imaging performed optimally so that it was commenced within five minutes of injection) in the detection of CAD. METHODS: Planar and SPECT studies were performed in 44 patients with significant (> 70% stenosis) CAD, seven patients with borderline stenoses (50-69%) and in 18 patients with no significant CAD. RESULTS: The sensitivity of planar imaging was 66% which was higher than exercise ECG 54% (ns) but significantly lower than SPECT 86% (p < 0.005). The specificity of planar thallium scintigraphy was 100% which was higher than SPECT (83%) and significantly higher than exercise ECG 72% (p < 0.05). SPECT had a significantly higher sensitivity for LAD and single vessel disease than planar imaging and this was unrelated to a history of prior myocardial infarction. CONCLUSION: Even when planar imaging is timed optimally to minimise the impact of early redistribution, SPECT is more sensitive than either planar imaging or exercise ECG in the detection of CAD, but its specificity is lower.

Adult↗
PubMed1996

Phase I/II study of iodine 125-labeled monoclonal antibody A33 in patients with advanced colon cancer.

PURPOSE: A phase I/II study was designed to determine the maximum-tolerated dose (MTD) of iodine 125-labeled monoclonal antibody A33 (125I-mAb A33), its limiting organ toxicity, and the uptake and retention of radioactivity in tumor lesions. PATIENTS AND METHODS: Patients (N = 21) with advanced chemotherapy-resistant colon cancer who had not received prior radiotherapy were treated with a single 125I-mAb A33 dose. 125I doses were escalated from 50 to 350 mCi/m2 in 50-mCi/m2 increments. Radioimmunoscintigrams were performed for up to 6 weeks after 125I-mAb A33 administration. RESULTS: All 20 patients with radiologic evidence of disease showed localization of 125I to sites of disease. Twelve of 14 patients, who underwent imaging studies 4 to 6 weeks after antibody administration, had sufficient isotope retention in tumor lesions to make external imaging possible. No major toxicity was observed, except in one patient with prior exposure to mitomycin who developed transient grade 3 thrombocytopenia. Although the isotope showed variable uptake in the normal bowel, gastrointestinal symptoms were mild or absent, and in no case did stools become guaiac-positive. The MTD was not reached at 125I doses up to 350 mCi/m2. However, cytotoxicity assays demonstrated that patients treated with the highest dose had sufficiently high serum levels of 125I-mAb A33 to lyse colon cancer cells in vitro. Among 21 patients, carcinoembryonic antigen (CEA) levels returned to normal in one patient and decreased by 35% and 23%, respectively, in two patients; one additional patient had a mixed response on computed tomography. Additional, significant responses were observed in those patients treated with chemotherapy [carmustine [BCNU], vincristine, flourouracil, and streptozocin [BOF-Strep]) after completion of the 125I-mAb A33 study. CONCLUSION: Low-energy emission radioimmunotherapy with doses of up to 350 mCi/m2 of 125I-mAb A33 did not cause bowel or bone marrow toxicity. The modest antitumor activity in these heavily pretreated patients is encouraging because of lack of toxicity at the doses studied. The long radioactivity retention in tumors suggests that isotopes with a long half-life may have a therapeutic advantage, based on calculated dose delivery to tumor versus normal tissue. Due to the low bone marrow dose, further 125I trials with humanized mAb A33 are warranted, and controlled studies must be conducted to evaluate the combination of radioimmunotherapy and chemotherapy.

Adult↗