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PubMedDate not supplied

Preliminary study on radioimmunodiagnosis of experimental tumor models using technetium-99m-labeled anti-C-erbB-2 monoclonal antibody.

AIMS AND BACKGROUND: One of the great challenges of oncology is to improve methods for early tumor detection. Diagnosis of premalignant lesions and early stage primary tumors is crucial for the success of cancer therapy and increased survival rates. Growth factor receptors localized to the cell membrane play a vital role in cancer. Monoclonal antibodies labeled with radioisotopes have been used extensively for radioimmunodiagnosis and radioimmunotherapy of various malignancies. A preliminary study on immunoscintigraphy was carried out on animal tumor models using 99mTc-labeled monoclonal antibody CIBCgp185 generated against the CerbB-2 oncoprotein with a view to develop technologies for in vivo radioimmunodetection and localization of human breast cancer. METHODS: Mammary tumor xenografts induced using BT474 cells, a breast carcinoma cell line showing overexpression of C-erbB-2, were used for immunoscintigraphic studies. RESULTS: Scintigrams showed high radiolabel uptake by the tumor tissue of the mice belonging to the experimental group, whereas in control animals no radiolabel uptake was visualized. Biodistribution studies correlated well with scintiscans. CONCLUSIONS: The results indicate the potential application of this monoclonal antibody for in vivo diagnosis of occult malignancies of tumors with overexpression of C-erbB-2.

Animals↗
PubMedDate not supplied

Clinical utility of radioimmunoscintigraphy of non-Hodgkin's lymphoma with radiolabelled LL2 monoclonal antibody, LymphoSCAN: preliminary results.

AIMS AND BACKGROUND: Adequate clinical staging of non-Hodgkin's lymphoma patients is essential because only localized disease can be treated satisfactorily. Many imaging procedures are necessary to stage the disease accurately. The objective of this study was to evaluate the efficacy of an antilymphoma antibody in the Fab' fragment form, labelled with 99mTc, to detect malignant lesions. METHODS: Radioimmunodetection (RAID) with 99mTc-labelled B-cell lymphoma monoclonal antibody IMMU-LL2-Fab' (LymphoSCAN; Immunomedics, Morris Plain, NJ, USA) was investigated in 10 patients (5 females and 5 males; age range, 20-72 years) with histologically proved non-Hodgkin's lymphoma. Of the 10 lymphomas, 7 were intermediate grade and 3 were low grade. Whole body images with multiple planar views were obtained at 30 min, 4-6 and 24 h after i.v. injection of 1 mg LL2-Fab' labelled with 740-925 MBq of 99mTc. SPET of the chest or abdomen was performed in all patients 5-8 h after the immunoreagent injection. RESULTS: No adverse reactions were observed in any patient after Mab infusion, and no appreciable changes were seen in the blood counts, renal or liver function tests. A total of 18 of 21 (85.7%) lymphoma lesions were detected by RAID. All the tumor localizations were confirmed by clinical examination and with other imaging techniques, such as CT scan, MRI or gallium scan. In this series of patients no false-positive results were noted. As regards the biodistribution of the immunoreagent, no appreciable bone marrow activity was seen; splenic targeting was demonstrated in all patients; the tumor-to-non-tumor ratios ranged from 1.2 to 2.8 ad measured by the ROI technique; no difference in uptake was noted for different tumor grades. The images obtained 24 h after injection did not reveal new lesions, but areas of doubtful uptake were seen as positive focal areas in the delayed scan. CONCLUSIONS: LymphoSCAN seems to be useful for detection, staging and follow-up of non-Hodgkin's lymphoma patients.

Adult↗
PubMed1995

Diagnosis of breast carcinoma with radiolabeled monoclonal antibodies (MoAbs) to carcinoembryonic antigen (CEA) and human milk fat globulin (HMFG).

The current study attempted to assess the potential proficiency of radioimmunodetection (RAID) of primary, residual, multicentric, and recurrent breast carcinoma using two radiolabeled murine monoclonal antibodies (MoAbs), anti-human milk fat globulin (HMFG1) labeled with iodine (123I) and anti-carcinoembryonic antigen (CEA) labeled with technetium (99Tc). Thirteen patients with suspicious clinical and/or mammographic primary or recurrent breast carcinoma were studied in a phase I-II prospective, consecutive, nonrandomized, noncontrolled study. Five patients received intravenous infusion with 0.5-2.0 mg anti-CEA MoAb type CYT 380 labeled with 99Tc [13-22 millicurie (mCI)] and 8 patients received intravenous infusion with 0.25-1.0 mg anti-HMFG1 MoAb (Unipath, U.K.) labeled with 123I (4-17 mCI). Both MoAbs used in this study demonstrated ability to bind specifically to breast cancer lesions, resulting in successful RAID in 10 of 12 of studied patients (5 of 5 patients in the anti-CEA-99Tc and 5 of 7 in the anti-HMFG-123I group--accuracy 83.3%). One patient was excluded due to protocol violation. Seven patients had true-positive scans when correlated with surgery (sensitivity 87.5%). The MoAb scans accurately diagnosed lesions in 3 of the 4 primary invasive breast carcinomas confirmed histologically. Presence of residual carcinoma following wide excision was established in 1 of 2 patients and presence of soft tissue metastases in 3 patients. Three patients had true-negative scan (specificity 75%): 2 patients presented with suspicious mammographic recurrence postlumpectomy and 1 patient had questionable soft tissue recurrence. One patient with primary breast carcinoma had a false-negative scan and another had a false-positive scan in the presence of fibrosis following lumpectomy and radiation therapy. No adverse reactions were noted in the patients studied. RAID findings were confirmed by immunohistochemistry in 6 of 9 cases studied. Our data suggest that radiolabeled MoAbs used in this study are potentially useful diagnostic agents for evaluation of primary or recurrent breast carcinoma, particularly in the areas where conventional methodology is limited.

Adult↗
PubMed2000

Interferon-alpha-2b immunoconjugate for improving immunoscintigraphy and immunotherapy.

UNLABELLED: A pretreatment with a single dose of an immunoconjugate (IC) that promises to enhance tumor uptake and decrease liver uptake of radiolabeled monoclonal antibodies (MAbs) might be of use in radioimmunodetection and radioimmunotherapy (RIT). We have shown previously that an interferon (IFN)-MAb (1:1) immunoconjugate (IC) enhances tumor uptake by a factor of 2 or more and reduces liver uptake by 50% in nude mice bearing human tumors. The aim of this study was to determine whether IFN modulates antigenic expression and to ascertain the most effective route of its administration, the optimal quantity to be administered, and the optimal duration of time to lapse between the administration of IC and the radiolabeled MAb. METHODS: IFN-alpha-2b and anticarcinoembryonic antigen-F6 (IgG2a) MAb were conjugated (1:1), and F(ab')2 of the MAb was labeled with 99mTc. Human colorectal tumors were grown in nude mice by implanting 5 x 10(6) LS174T confluent cells grown in culture. Mice, 5 in each group, received 20 x 10(3) IU intravenously, intramuscularly, or intraperitoneally and 40 x 10(3), 60 x 10(3), and 80 x 10(3) IU intravenously 30 min before the intravenous administration of 25.9 MBq 99mTc/20 microg F(ab')2. Mice in the control groups received 99mTc-F(ab')2 but not the conjugate. Twenty-four hours later mice were killed and imaged, and tissues were removed for quantitative (percentage injected dose/g [% ID/g]) distribution of 99mTc. RESULTS: In all conjugate-receiving mice, the tumor uptake was higher and the liver uptake was lower (P < 0.01) than that in the control mice with the exception of liver uptake, which was not significantly different in mice receiving 80 x 10(3) IU conjugate. The optimal results were apparent in mice pretreated with 40 x 10(3) IU conjugate in which tumor uptake was enhanced by a factor of 2.3 (4.8 +/- 0.5 %ID/g versus 11 +/- 0.7 %ID/g; P < 0.01). The renal uptake remained unchanged, and the tumor-to-muscle ratios increased from 11.5 +/- 6.8 to 14.6 +/- 3.9, and the tumor-to-blood ratios increased from 4.4 +/- 1.8 to 8.3 +/- 2.4. The liver uptake decreased from 9.5% +/- 1% to 5% +/- 1.6%. Results were attributed to enhanced tumor blood flow, increased antigenic expression, and blocking of hepatic nonspecific Fc receptors. CONCLUSION: A pretreatment with IFN-MAb conjugate is a worthwhile approach to consider in radioimmunoscintigraphy and RIT.

Animals↗
PubMed2000

[Iodine-125 labeled monoclonal antibody 3H11: in radioimmunoguided surgery for primary gastric cancer].

OBJECTIVE: To evaluate the clinical usefulness of iodine-125 labeled monoclonal antibody (MAb) 3H11 in radioimmunoguided surgery (RIGS) for patients with gastric cancer. METHODS: Thirty-five patients with primary gastric cancer were enrolled. Via endoscopy, iodine-125 labeled MAb 3H11 was injected into submucosa around the tumor. All patients underwent surgery 4 to 11 days after administration. Intraoperative radioimmunodetection was performed using a hand-held gamma-detecting probe. The counts of target sites were obtained, and tumor-to-normal tissue (T/NT) ratios were calculated. The T/NT ratio of 3.5:1 was taken as the lowest threshold value of positive gastric wall infiltration, and 3.0:1 for lymph node metastasis. Serial sections of those RIGS-positive lymph nodes, which were originally diagnosed as negative by routine histology, were made. Immunohistochemical staining was performed to detect the existence of lymphatic micrometastasis. RESULTS: Of thirty-five patients, 33 underwent RIGS successfully. The accuracy rate in detecting tumor infiltration of the incision margins was 97.0%, and the specificity 98.5%. In the group of patients with an interval of 6 to 8 days between injection and operation (n = 25), the RIGS results were satisfying. For the detection of lymphatic metastasis, the sensitivity of RIGS was 83.6%, the specificity 95.0%, and the accuracy 91.3%. The existence of lymphatic micrometastasis were verified immunohistochemically in 52.6% (10/19) of those RIGS positive but histologically negative lymph nodes. CONCLUSION: This study validates the use of iodine-125 labeled monoclonal antibody 3H11 for the intraoperative detection of carcinomatous lesions in gastric cancer.

Adult↗
PubMed1992

[Significance and application of anti-malignant hepatoma MAb HAb18 in radioimmunal diagnosis of human hepatocellular carcinoma].

In this study, 125I or 131I labelled intact IgG and its F(ab')2 fragments of an antihuman hepatoma monoclonal antibody, HAb18, was used for in vivo radioimmunoimaging of malignant hepatomas. Clear imaging of the tumor was obtained in 168 hours for intact IgG or in 72 hours for F(ab')2 fragments after iv injection or via selective catheterization of the arteriae hepatica communis. In addition, 99mTc-PHY (500 microCi) was simultaneously injected for static scanning of the liver, with which the tumor appeared as defects. All the 20 patients in this study were operated and the lesions were pathologically examined to verify the imaging results. The tumor: liver isotopic ratios were 2.15 +/- 0.15 and 2.63 +/- 0.21 for intact IgG and F(ab')2 fragments, respectively. In other vital organs, such as heart, brain, spleen, lungs and kidneys, as well as non-hepatoma neoplasms, including 3 cases of liver cavernous hemangioma and 2 cases of gastric cancer metastasized to the liver, no radioisotopic concentration was observed. Both the labelled IgG and F(ab')2 fragments had the same targeting potential, but a better contrast was obtained with F(ab')2 fragments. Furthermore, its clearance rate was faster than intact IgG. The smallest tumor diagnosed with this antibody was 0.5 cm in diameter and the positive rate for imaging primary hepatoma was 86.7% (13/15). The results obtained in this study promisingly indicate that HAb18 antibody may become the first choice for the early radioimmunodetection of human hepatoma.

Carcinoma, Hepatocellular↗
PubMed1992

Anti D dimer monoclonal antibodies: a possible scintigraphic agent for immunodetection of thrombi.

The aim of this work was to produce a MoAb able to react with clots but not with fibrinogen. Monoclonal antibodies directed towards DD dimers, against specific products of plasmic digestion of cross-linked fibrin, were obtained. One of these antibodies, F 60/43/8, showed a 1.79 x 10(9) l mol-1 binding constant in spite of the presence of fibrinogen at a 4000 times greater concentration than the cross-linked fibrin. In vitro studies with 125I-F(ab')2 of F 60/43/8 showed that 34-80% of the radioactivity can be found in human clots, in the presence of physiologic concentrations of fibrinogen, and that 96-h washing does not remove the labelled F(ab')2 from the clot. 131I-F(ab')2 was injected into rabbits in which a clot had formed in an artery (six rabbits) or in a vein (six rabbits) of the left ear. Scintigraphic images of the clot were always obtained. In conclusion, the results of this work suggest that F 60/43/8 may be used as a specific antibody for the radioimmunodetection of thrombi.

Animals↗
PubMed1995

Improved staging of B-cell non-Hodgkin's lymphoma patients with 99mTc-labeled LL2 monoclonal antibody fragment.

Radioimmunodetection (RAID) with the 99mTc-labeled Fab' fragment of monoclonal antibody (MoAb) LL2 has been reported to have a high lesion detection rate for malignant lymph nodes as well as for visceral and skeletal tumor masses (20). Our purpose in this study was to evaluate the safety and staging efficacy of the 99mTc-labeled Fab' fragment of MoAb LL2 in patients with various grades and stages of B-cell non-Hodgkin's lymphoma (NHL). Thirty adult patients, 13 male and 17 female, ranging in age from 20 to 80 years, with at least one biopsy-proved malignant node (> or = 0.5 cm) and a Karnofsky performance score of > or = 60% were enrolled in this study. Patients underwent selected planar and single photon emission computed tomographic imaging at 6 and 18 h after receiving an i.v. infusion of 0.25-1 mg of LL2 Fab' fragment labeled with 25-30 mCi of 99mTc. RAID findings were compared with physical examination, chest radiography, computed tomography, magnetic resonance imaging, and bone and 67Ga scan findings. The RAID scan was positive in all but three patients. The sensitivity for known lesions was 90% and for suspected lesions, 89%, with an overall positive predictive value of 96%. Twenty-nine of the 30 patients had either low- or intermediate-grade NHL. Fifteen of 16 (94%) low-grade patients were correctly staged by RAID; three of these patients were correctly upstaged. Twelve of the 13 (92%) intermediate-grade patients were correctly staged by RAID; two of these patients were correctly upstaged. The high-grade NHL patient was staged correctly by RAID. Infused doses of 99mTc-labeled LL2 Fab' of 0.5 and 1.0 mg did not affect lesion sensitivity. The RAID sensitivity decreased as the total tumor burden increased > or = 100 g. On the basis of these initial results, the 99mTc-labeled Fab' fragment of MoAb LL2 (LymphoScan) seems to yield useful clinical information, especially for the staging of B-cell NHL patients who do not have bulky disease (i.e., tumor burdens of < or = 100 g).

Adult↗
PubMed1994

[The experimental study of anti-human AFP variant McAb in radioimmuno-detection and radioimmuno-therapy of human hepatocellular carcinoma model in nude mice].

Anti-human AFP variant monoclonal antibody (AFP-R-LCA McAb) was labeled by 131I and injected intraperiton ealy. The 131I-AFP-R-LCA McAb was gathered in tumor of nude mice bearing human hepatocellular carcinoma (HCC). The tumor/liver radioactivity redio was 5.2, but normal mice IgG labeled by 131I-(131-mIgG) or free 131I was not gathered in tumor and distributed everywhere in average. The group of 131I-AFP-R-LCA McAb was positively visualized by gamma camea. The test showed that 131I-AFP-R-LCA McAb cured the nude mice bearing HCC. The tumor inhibition rate in 131I-AFP-R-LCA McAb group at the 4th week after treatment was significantly higher than those of the other groups (85%, 45%, 20%, 7% respectively, P < 0.05). The result showed that the AFP-R-LCA McAb have strong affinity and special combination to HCC cells and it can be recognized as a carrier for radioimmunodetection and radioimmunotherapy.

Animals↗
PubMedDate not supplied

Feasibility of radioimmunoguided surgery of colorectal carcinoma using indium 111 CEA specific antibody and simulation with a phantom using 2 steps targetting with bispecific antibody.

The study was undertaken to define the potential use of radiolabelled (Indium 111 or Technetium 99 m) carcinoembryonic antigen specific antibody (CEA f(ab')2) for the radioimmunodetection of colorectal cancer using an intraoperative hand-held gamma probe. A clinical study performed with ten patients showed that tumor with good uptake of CEA specific antibody could be detected with sufficient contrast only in two patients. Results of a biodistribution study performed with tumor fragment and normal tissue countings in a gamma counter showed high tumor uptake in five patients. There was no correlation between tumor uptake and the count rates measured intraoperatively. To increase the signal/background of the gamma probe, a simulation study with a peritoneal cavity phantom was performed. We determined the efficiency of a two steps targetting method compared to the direct method. We simulated different tumor sizes with plexiglas balls (0.5, 1, 2, 5 ml) and tested two scintillators (NaI, BgO). Experiments were performed with 111 In and 99 m Tc. The two steps targetting method was better than direct method. The results of simulation with direct method radiolabelled with 111 in confirmed our clinical study: no efficiency of a gamma probe for the surgeon to detect a tumor. However the two steps targetting method (indirect labelling method) was very encouraging to detect tumors (size 1 and 2 ml) and definitively convincing with 99 m Tc.

Antibody Specificity↗
PubMed1994

In vivo behavior of 111In-labeled monoclonal anti-prostatic acid phosphatase antibody after intraprostatic and intravenous injections.

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)

Acid Phosphatase↗
PubMedDate not supplied

Radioimmunoassisted follow-up and surgery vs traditional examinations and surgery after radical excision of colorectal cancer.

The authors report their experience in the radioimmunodetection of recurrent colorectal cancer in comparison with traditional examinations. 485 patients were studied after radical surgery for colorectal cancer: 168 (Group 1) were studied with a radioimmunoassisted follow-up plan including: Immunoscintigraphy (IS), serum markers assays, Radioimmunoguided Endoscopy (RIGE), Intraoperative Radioimmuno-localization (IORIL) in case of reoperation; 317 (Group 2) underwent a protocol with traditional examinations. In 24 patients of Group 1 IS was performed even at the time of their admission for primary cancer. 7 patients underwent RIGE for primary cancer and 16 in the follow-up. IORIL was performed in 12 patients with primary cancer and in 16 in the course of reoperation. The radioimmunodiagnostic methods were performed after a single administration of the radiolabeled MAb (111In F(ab')2 a-CEA and 111In B72.3). The radioimmunoassisted follow-up plan detected a greater number of recurrences than traditional examinations (27% vs 13%). The rates of radical reoperation in Group 1 and 2 were 61% and 37% respectively. 33% of the patients of Group 2 were alive 24 months after radical reoperation vs 62.5% of the patients of Group 1. Immunoscintigraphy demonstrated a good sensitivity and specificity, mainly in the detection of pelvic recurrences (sens. 92%, spec. 84%). The radioimmunoassisted follow-up plan was well accepted by the patients. RIGE led to the detection of 3 periluminal recurrences of rectal cancer that traditional investigations failed to demonstrate and in 5 cases influenced the patients management. IORIL detected minimal tumor foci (2 mm.) where pre and intraoperative study were negative, while the histopathologic examination gave evidence of tumor. Considering that the costs of the radioimmunodiagnostic methods and of traditional examinations are very similar, we can conclude that the radioimmunoassisted follow-up plan has a favorable cost/benefit rate and a remarkable impact on the treatment of patients with colorectal cancer.

Aged↗
PubMed1993

Three-step tumor pre-targeting in lung cancer immunoscintigraphy.

Radiolabelled MoAbs have been used in both the diagnosis and the treatment of a variety of tumors. Recently, a three-step tumor pre-targeting strategy has been proposed to overcome one of the major limiting factors in radioimmunodetection: the low tumor-to-background ratio. We evaluated this pre-targeting protocol in 10 patients diagnosed as having pulmonary carcinoma. One milligram of biotinylated anti-CEA MoAb (FO23C5) was administered i.v. (1st step); 24 hours later 5 mg of avidin was injected i.v. (2nd step) followed by 100-500 ng of 111In-biotin (5 mCi) the day after (3rd step). Imaging was performed using single photon emission tomography (SPET). No toxicity and no adverse reactions were observed. Tumor was detected in 8 out of 10 patients. Mediastinal metastases were also localised in 2 out of 3 patients, and adrenal gland recurrency in 1 out of 2 patients. The tumor/background (normal lung), heart, liver and spine ratios were respectively 2.0, 1.0, 1.3 and 4.1 at 90 minutes post-injection. These preliminary data show that the three-step pretargeting method is safe and allows SPECT tumor localization soon after the injection of the radiolabel. In the future, the use of MoAbs with higher specificity could result in improved tumor-targeting, and in the possibility of lung cancer radioimmunotherapy.

Aged↗
PubMed1993

Colorectal cancer imaging with iodine-123-labeled CEA monoclonal antibody fragments.

This prospective, randomized multicenter study in 62 patients was designed to evaluate the efficacy and safety of radioimmunodetection (RAID) with 123I-labeled fragments, F(ab')2 and Fab', of IMMU-4, an anti-CEA monoclonal antibody (Immu-RAID-CEA). It was found that ImmuRAID-CEA was safe and disclosed colorectal cancer sites at least 1 cm in size. The positive predictive value by lesions was 77% initially, and increased to 91% after 7 mo of follow-up. Only one patient developed a low level of HAMA. In 17 patients with 32 surgically confirmed lesions, there were 9% true-positive lesions for CT when RAID was false-negative, and 22% for RAID when CT was false-negative. Either CT or RAID detected all 32 lesions. In this small series, therefore, RAID was shown to complement CT findings by confirming suspected tumors and disclosing new lesions which had previously been occult.

Adult↗
PubMed1997

Radiolabelled monoclonal antibodies in clinical and surgical oncology: a review.

Over the past decade, the role of immunoscintigraphy using radiolabelled monoclonal antibodies has been steadily growing in clinical oncology, and in particular, in radioimmunotherapy and radioimmunoguided surgery for the treatment of primary, recurrent, and metastatic colorectal, ovarian, gastric, and prostate cancer. Herein, the authors review the requirements for successful tumour radioimmunodetection and related procedures.

Antibodies, Monoclonal↗
PubMed1996

[Labeling of antihuman bladder carcinoma monoclonal antibody with a technetium-99m and radioimmunoimaging of human bladder carcinoma xenograft in nude mice].

Anti-human bladder carcinoma cell line BIU-87 monoclonal antibody-BDI-1 was labeled with 99mTc by direct mercaptoethanol reducing method. Quality control tests showed that the labeling yield was 69.9%; the radiochemical purity was higher than 90%; the immunoreactive fraction of 99mTc-BDI-1 was 81% and the association constant was 1.22 x 10(-9) M-1. The radioimmunoimaging of human bladder carcinoma xenograft in nude mice and the biodistribution of 99mTc-BDI-1 were studied. After having been scintigraphed at three time intervals (at 4, 16 and 22 hour), the animals were sacrificed for biodistribution of 99mTc-BDI-1. Tumor can be seen clearly at 22 hour after intravenous injection of 99mTc-BDI-1; %ID/g (percentage of the injected dose per gram of tissue) of tumor was 20.70, the average T/NT was 10.52, the minimum T/NT was 2.90 (tumor/kidney) and the maximum T/NT was 20.70 (tumor/small intestine or muscule). The results above indicated that 99mTc-BDI-1 can be used for radioimmunodetection of human bladder carcinoma in vivo and BDI-1 may be suitable as a targeting device in patients.

Animals↗
PubMed1997

Manipulation of blood clearance to optimize delivery of residualizing label-antibody conjugates to tumor cells in vivo.

UNLABELLED: We have attempted to improve the therapeutic index of radioimmunotherapy by manipulating the blood clearance rate and the catabolism of the radiolabel. The general strategy is to allow the antibody (Ab) to circulate in the blood for 2-3 days, then to clear it rapidly by a method that delivers the Ab to hepatocytes. In addition, the radiolabel selected has two key properties: it is a residualizing label (which is lysosomally trapped after catabolism), so it is retained well by tumor cells, but is excreted rapidly by hepatocytes into bile. METHODS: In initial experiments, three residualizing radiolabels were tested for their rate of excretion after specific delivery in vivo to either hepatocytes, via galactosylated Ab, or Kupffer cells, via immune complexes. A label showing rapid biliary excretion only after delivery to hepatocytes, (111)In-benzyl-diethylenetriamine tetraacetic acid, was then used for radioimmunodetection in a protocol of delayed rapid blood clearance in which clearance was by hepatocytes. This was achieved by using galactosylated Ab, combined with temporary inhibition of the asialo-glycoprotein receptor on hepatocytes. Ab RS11 and the lung adenocarcinoma Calu-3 xenograft in nude mice were used. Control experiments were performed with a conventional 125I label and with 125I-dilactitol-tyramine. RESULTS: Indium-benzyl-diethylenetriamine tetraacetic acid was identified as a label that was excreted more rapidly from hepatocytes than from Kupffer cells, by biliary excretion. Using this radiolabel with delayed rapid blood clearance, very high tumor/blood ratios were obtained, 166:1 at day 3, but tumor/normal tissue ratios for other tissues were not as high. There appeared to be some uptake of the radiolabel by all normal tissues tested, including the lungs and muscle. Dosimetry calculations suggested that the therapeutic index was no better than with a simple Ab injection. CONCLUSION: Antibody catabolism can be directed towards either hepatocytes or Kupffer cells, and this difference can strongly affect the excretion rate of radiolabels, since only hepatocytes can excrete degradation products into bile. Processing will also depend on the particular radiolabel. These factors are particularly important for protocols involving delayed rapid blood clearance, since liver uptake is so rapid. The methods described should stimulate other approaches of manipulating Ab blood clearance and radiolabel catabolism to achieve improved therapeutic results.

Animals↗
PubMed1998

Radioimmunolocalization of primary and metastatic breast cancer.

The appropriate therapy for breast cancer depends mainly upon early and reliable tumor detection, correct tumor staging and accurate re-staging after therapy. Current radiological imaging methods are based primarily on morphology resulting in high sensitivity but lacking specificity. Established nuclear medicine techniques are sensitive but not very specific. To improve specificity, a number of monoclonal antibodies, selected against a particular tumor-associated antigen expressed on the surface of breast cancer cells, have been radiolabeled for imaging in vivo tumor localizations. In theory, radioimmunodetection offers the potential to demonstrate cancer cells even in subradiological disease, or when anatomy-based imaging methods may be unable to distinguish the nature of an evident mass, making the differential diagnosis between an inflammatory reaction, a postsurgical fibrosis, or a truly viable tumor impossible. Suspected tumor recurrence indicated by increasing tumor marker levels could be another clinical indication for radioimmunolocalization, even if standard imaging modalities are negative. A large number of antibodies against different epitopes of human neoplastic breast tissue have been investigated previously. However, a highly specific and sensitive monoclonal antibody for immunoscintigraphy and radioimmunotherapy has not yet been found. This review addresses tumor-biological considerations, radioisotopes and radiolabeling methods, tumor targets and different monoclonal antibodies used for immunoscintigraphy (incl. SPECT amd PET) of breast cancer.

Antibodies, Monoclonal↗