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At least 19 recordsLinked to original sources
PubMed1993

Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts.

Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60Co teletherapy unit. Control groups received saline, unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Subcutaneous CEA-expressing LS174T human colon carcinoma tumors were measured over time. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 microCi, 175 microCi, and 225 microCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 microCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 microCi and 175 microCi resulted in growth delays of 9 and 19 days, respectively. The 120 microCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity.

Animals↗
PubMed1989

[Radioimmunotherapy combined with chemotherapy and immunotherapy for nude mice bearing human hepatocellular carcinoma].

A comparative study of multiple modalities, radioimmunotherapy combined with cisplatin and MBV was made. The tumor size and macrophage activity (acid phosphatase) were measured after treatment. The results showed that the tumor inhibition rates were 48, 55, 74, 76, 79% in radioimmunotherapy, cisplatin, radioimmunotherapy + MBV, radioimmunotherapy + cisplatin and radioimmunotherapy + MBV + cisplatin groups, respectively. Radioimmunotherapy was effective in controlling tumor growth, especially in sequential treatment by two injections. Both cisplatin and MBV could increase therapeutic effect of radioimmunotherapy. Therefore, combination of the three modalities is the best choice for tumor growth control. The effectiveness of MBV may be related to the increase of macrophage activity. Preliminary clinical results were satisfactory. Decline in serum AFP level and shrinkage of tumor were observed in 80% (12/15) and 65% (13/20) of the patients. It is suggested that combination of multiple treatment modalities may provide an important approach to treat moderately advanced liver cancer.

Animals↗
PubMed1994

Experimental radioimmunotherapy. A brief overview.

This overview highlights the use of experimental models in selecting monoclonal antibodies and radiolabels with promise for clinical radioimmunotherapy, discusses some of the experimental therapeutic approaches being studies in these models, and reviews some of the limitations of animal models caused by the allometric and other differences between man and mouse. These differences in scale must be considered when attempting to extrapolate animal radioimmunotherapy study data to human trials of radioimmunotherapy. With appropriate recognition of their limitations, experimental models of radioimmunotherapy have proven valuable and will continue to play a critical role as the place to first study innovations in radioimmunotherapy, before extension of the most promising reagents and treatment concepts into clinical therapeutic trials.

Animals↗
PubMed1992

[Evaluation of radioimmunotherapy in the multimodality treatment of hepatocellular carcinoma (HCC)].

The evaluation of radioimmunotherapy using 131I-anti HCC isoferritin IgG antibody in the multimodality treatment of HCC was reported. Forty three patients with surgically verified unresectable HCC have been treated by radioimmunotherapy as a part of multimodality treatment during 1985-1990. The short-term responses and prolong survival were compared with that in control group of 39 patients with HCC receiving conventional multimodality treatment. The rates of tumor shrinkage, AFP level decline and second resection in radioimmunotherapy group were 67.4% (29/43), 69.6% (16/23) and 30.2% (13/43) respectively, significantly higher than those in control group 23.1% (15/39), 40.0% (8/20) and 10.3% (4/39) respectively. The 1, 3, 5-year survival rates were 61.5%, 40.4% and 35.5% in radioimmunotherapy group, however, in control group were 51.3%, 20.1% and 15.5%, respectively. The results suggested that radioimmunotherapy is one of modalities of choice, particularly for the treatment of unresectable HCC in the multimodality treatment regimen.

Adult↗
PubMed1992

5-Iododeoxyuridine increases the efficacy of the radioimmunotherapy of human tumors growing in nude mice.

Recently, there has been much interest in the use of radionuclide conjugated monoclonal antibodies for the treatment of human malignancies. One way to potentially maximize the therapeutic effectiveness of radioimmunotherapy would be to sensitize tumor cells to the radiation dose delivered by the antibody. Since radioimmunotherapy can potentially treat disseminated disease, including micrometastasis, we chose to study a halogenated pyrimidine radiosensitizer, a class of compounds that affect nonhypoxic cells. 5-Iododeoxyuridine, administered with pyrimidine metabolism modulators, increased the therapeutic effectiveness of radioimmunotherapy, resulting in individual cures of human tumors growing in BALB/c nu/nu (nude) mice. 5-Iododeoxyuridine was administered with N-(phosphonacetyl)-L-aspartic acid and 5-fluoro-deoxycytidine plus tetrahydrouridine. This drug treatment was combined with radioimmunotherapy using 131I conjugated to a monoclonal antibody, Mc5. Mc5 binds to a mucin component of the human milk fat globule. This antigen is expressed on the surface of MX-1 cells, the transplantable human tumor used in this study. Tumor-bearing mice treated with both the drug protocol and 131I-Mc5 (540 microCi, 10 microCi/micrograms) showed a regression in average tumor volume. The average tumor volume was reduced below the initial size at treatment for 50 days; two of five cures were obtained. Neither cures nor regressions were observed with either the drug or antibody treatments alone. Our results indicate the potential for increasing the therapeutic effectiveness of radioimmunotherapy of human solid tumors with halogenated pyrimidines.

Animals↗
PubMed1995

Selection of tumor-specific epitopes on target antigens for radioimmunotherapy of breast cancer.

Evidence is presented for two different breast epithelial antigens that some epitopes have greater tumor specificity and are more effective targets for radioimmunotherapy than others. The two antigens, which are major components of the human milk fat globule membrane, are breast mucin and a M(r) 46,000 glycoprotein (BA46). Of five monoclonal antibodies (Mc5, Mc1, BrE-1, BrE-2, and BrE-3) against breast mucin, all recognize overlapping amino acid epitopes on the tandem repeat domain. However, each have unique and different tissue and tumor specificities and unique epitope structures on the fully glycosylated breast mucin. In preclinical studies, radioimmunoconjugates of all five monoclonal antibodies inhibit growth of transplantable breast tumors in immunodeficient mice. In human clinical trials, radioiodinated Mc5 was very poor in localizing breast tumor metastases. On the other hand, 111In-labeled BrE-3 imaged almost 90% of breast tumors and showed promise in radioimmunotherapy when labeled with 90Y. The failure of Mc5 in clinical trials may be partly attributed to the high levels of its epitope on circulating mucin compared to the epitope of BrE-3. The Mc5 binding affinity increased significantly with glycosylation, while the BrE-3 epitope was masked by glycosylation. The BA46 glycoprotein is a breast tumor-associated membrane antigen containing an NH2-terminal, epidermal growth factor-like domain into which a cell adhesion sequence (RGD) is inserted and a COOH-terminal domain with homology to the phospholipid binding C1/C2 domain of coagulation factors V and VIII. It promotes cell attachment in an RGD-dependent manner. Monoclonal antibody Mc8, which binds to the C2-like domain, is only moderately effective in experimental radioimmunotherapy, while Mc3, which binds an epitope in the EGF-like RGD domain, was highly effective in destroying breast tumors in nude mice. With 90Y-labeled Mc3, 6 of 7 mice are cured of the tumors. These results indicate that by selecting appropriate monoclonal antibodies, a normal antigen can be used as a target for radioimmunotherapy.

3T3 Cells↗
PubMed1991

Radioimmunotherapy of malignancies.

The critical issues in radioimmunotherapy are highlighted, and novel ways of improving the therapeutic indexes of radioimmunotherapeutic agents are outlined. The use of radioactively labeled monoclonal antibodies to treat malignant tumors has been investigated in animals and humans. Radionuclides suitable for labeling antibodies for such use include iodine 125, iodine 131, yttrium 90, rhenium 188, and copper 67. Radiobiological factors to be considered in radioimmunotherapy include the size and density of the tumor and the ability of a radiolabeled antibody to penetrate the tumor nodule. The dose of radiation required to destroy a tumor varies; however, the whole-body dose must not exceed 200 rads to avoid irreversible toxicity to the bone marrow. Despite the theoretical inadequacy of radiation doses to tumors indicated by conventional dosimetry, responses have been observed in animals and humans. More reliable and accurate dosimetric methods are under development. The induction of human antimouse antibodies can alter the pharmacokinetics of radiolabeled antibodies. Improving the therapeutic index of radioimmunotherapeutic agents may be achieved through regional therapy, administering a secondary antibody to improve clearance, combining radioimmunotherapy with external-beam irradiation, using an avidin-biotin conjugate system to deliver the radiolabeled antibodies, and addressing the problem of tumor antigen heterogeneity. Researchers are working to reduce or eliminate the clinical problems associated with radioimmunotherapy. Hematologic malignancies, such as lymphomas, are more likely than solid tumors to respond satisfactorily.

Animals↗
PubMed1990

Current status of animal radioimmunotherapy.

Progress in animal radioimmunotherapy has been reviewed by highlighting 22 successful experiments using human xenografts in rodent models. Significant tumor growth delay has been observed in all experiments with five groups reporting tumor control 100 days post-tumor implantation. The radiobiological significance of these experiments is analyzed through a proposed framework for the comparison of radioimmunotherapy to external beam therapy in both animals and humans. The limits of applicability of animal modeling to the clinical setting are evaluated in terms of intrinsic radiosensitivity, tumor volume effects, tumor bed effects, and the host defense mechanism. A generalized strategy for the development of clinical radioimmunotherapy is proposed based on utilization of radioimmunotherapy as a boost therapy in combination with external beam radiation.

Animals↗
PubMed1994

Overview of radiation myelotoxicity secondary to radioimmunotherapy using 131I-Lym-1 as a model.

The radiation dose-limiting toxicity from radioimmunotherapy has been myelotoxicity in the absence of bone marrow reconstitution (transplantation). Myelotoxicity can be assessed directly by biopsy examination of the bone marrow and indirectly by peripheral blood counts. In patients with B-cell malignancies, thrombocytopenia has been the initial and most severe manifestation of 131I-Lym-1 radiation toxicity from treatment. Manifestations of myelotoxicity varied greatly among the patients and from one treatment dose to another in the same patient, suggesting that additional factors were present. There was an increased likelihood of Grade 3-4 hematopoietic toxicity after 131I-Lym-1 treatment if the patient had peripheral blood cell abnormalities before undergoing 131I-Lym-1 treatment. Fractionation of the total 131I-Lym-1 dose was associated with less toxicity. In many patients, myelotoxicity could not be explained by marrow radiation dose (0.36 +/- 0.13 rads per administered mCi) from 131I-Lym-1 in the blood and body alone. Bone marrow examination and 131I-Lym-1 imaging usually provided evidence for additional marrow radiation from 131I-Lym-1-targeting of marrow malignancy and also for residual toxic effects from prior treatment in these patients. Immunohistologic and imaging examination of the bone marrow performed with the intended treatment antibody allowed assessment of extent of marrow malignancy and prediction of degree of myelotoxicity from subsequent treatment. Treatment programs (and protocols) for radioimmunotherapy should incorporate these methods into the decision process. Larger amounts of 131I-Lym-1 can be used in patients selected to have relatively normal peripheral blood cell counts and normocellular bone marrows uninvolved by the malignancy. These observations appear to be relevant to the maximum tolerated dose in radioimmunotherapy for other malignancies as well.

Antibodies, Monoclonal↗
PubMed1994

Radiation dosimetry for radioimmunotherapy. An overview of current capabilities and limitations.

BACKGROUND. The two major uncertainties associated with absorbed dose calculations involve: (1) measurement errors from assessment of radioactivity in specific organs and tissues by direct counting; and (2) application of standard anthropomorphic and biokinetic models for dose assessment. Uncertainties in direct counting result from the inherent difficulty of measuring radioactivity inside the body. Although the system recommended by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine provides a general framework and conceptual basis for the dosimetry of administered radiopharmaceuticals, it does not provide complete methods for assessing some of the more important quantities of interest in radioimmunotherapy, such as dose to tumors and descriptions of spatial dose distributions within tissues. Current MIRD anthropomorphic models are only crude representations of the human body. Generalized biokinetic models used in the MIRD system may vary considerably from the actual biokinetics of radiolabeled compounds in the body. This review describes limitations of the present MIRD system for radioimmunotherapy; they include assumptions used in treatment planning and the lack of specific methods for tumor dosimetry, multi-cellular dosimetry, microdosimetry, small animal dosimetry, and uncertainty analysis. CONCLUSIONS. Treatment planning for radioimmunotherapy requires patient-specific organ models and customized biokinetic parameters. Improvements are also needed in marrow dosimetry to account for the amount and distribution of red marrow relative to that found in adjacent source regions, skeletal structures, and circulating blood. Simplified assumptions with regard to the locally absorbed fraction of beta-particle energy in tissues adjacent to source regions should not be used when depth-dose profiles are needed; for example, radiation absorbed doses to intestinal walls should be calculated over the entire mass of tissue or described by absorbed-dose distributions. Additional research is needed to develop improved measurement techniques and computational methods to assess more accurately internal dose distributions within tumors and normal tissues.

Humans↗
PubMed1992

Does immunoscintigraphy serve clinical needs effectively? Is there a future for radioimmunotherapy?

Since 1980, immunoscintigraphy has been performed in thousands of patients, and its clinical value has been demonstrated for selective indications in malignant (early detection of recurrences of colorectal and ovarian carcinomas) and non-malignant (cardiovascular and inflammatory) pathology. However, many clinicians are not yet very convinced of its efficiency. Opinions range between favourable interest and marked scepticism. The causes of this inconclusive verdict include an often moderate target-to-background ratio in images, the immunogenicity of injected murine antibodies and the fact that a true benefit for the patient has not yet been clearly demonstrated in large series of patients. Future prospects could significantly improve this and involve the reduction of non-specific activity in normal tissues (to improve disease target contrast and thus make image interpretation easier) and the decreased immunogenicity of injected immunoconjugates (to permit repetition of examinations). Radioimmunotherapy, an innovative and promising approach, is still limited by numerous problems. The results of clinical studies are still inconclusive, being encouraging only for specific indications. In the future, pre-targetting techniques should allow the rapid elimination of radioactivity from normal tissues, resulting in a significant increase in tumour-to-normal tissue ratios. Progress is also required in the choice of radionuclides and labelling techniques and in methods for dosimetric estimations. The clinical indications of radioimmunotherapy after systemic injection will concern mainly radiosensitive tumours such as lymphomas, small-cell lung cancers and neuroblastomas. After endocavitary injection, radioimmunotherapy could prove efficient in the treatment of micrometastases of ovarian carcinomas. For all indications, this new approach should be combined with other therapeutic modalities.

Evaluation Studies as Topic↗
PubMed1995

Optimising the radioimmunotherapy of malignant disease: the broadening choice of carrier and effector moieties.

The treatment of cancer by radioimmunotherapy remains an experimental approach successful only in a limited number of selected disease conditions. One ground for optimism over the future of radioimmunotherapy lies in the fact that where cures have been obtained it has been despite the design of the immunoconjugate rather than because of it. As the choice of available functional components for conjugate construction increases, the process of evaluation and optimisation is underway. The replacement of the commonly used 131I with radionuclides possessing radiation characteristics more suited to particular disease states, and tailored to the behaviour of the carrier vehicle, should bring improved energy deposition within tumour while reducing whole body radiation burden. Similarly, the introduction of chemically or genetically engineered targeting molecules in place of conventional antibodies may bring improved pharmacokinetic characteristics and higher tumour accumulation. Optimisation of the therapeutic and carrier moieties employed in radioimmunotherapy should bring distinct improvements in clinical efficacy.

Animals↗
PubMed1993

Cell cycle alterations, apoptosis, and response to low-dose-rate radioimmunotherapy in lymphoma cells.

PURPOSE: In an attempt to elucidate some aspects of the radiobiological basis of radioimmunotherapy, we have evaluated the in vitro cellular response patterns for malignant lymphoma cell lines exposed to high- and low-dose-rate radiation administered within the physiological context of antibody cell-surface binding. METHODS AND MATERIALS: We used two different malignant lymphoma cell lines, a Thy1.2+ murine T-lymphoma line called EL-4 and a CD20+ human B-lymphoma line called Raji. Cells were grown in suspension cultures and exposed to high-dose-rate gamma radiation from an external 137Cs source or low-dose-rate beta radiation from DTPA-solubilized 90Y in solution. In some experiments, cells were pre-incubated with an excess of nonradioactive antibody in order to assess the effects of immunoglobulin surface binding during radiation exposure. Irradiated cells were evaluated for viability, cell-cycle changes, patterns of post-radiation morphologic changes, and biochemical hallmarks of radiation-associated necrosis and programmed cell death. RESULTS: The EL-4 line was sensitive to both high-dose-rate and low-dose-rate irradiation, while the Raji showed efficient cell kill only after high-dose-rate irradiation. Studies of radiation-induced cell cycle changes demonstrated that both cell lines were efficiently blocked at the G2/M interface by high-dose-rate irradiation, with the Raji cells appearing somewhat more susceptible than the EL-4 cells to low-dose-rate radiation-induced G2/M block. Electron microscopy and DNA gel electrophoresis studies showed that a significant proportion of the EL-4 cells appeared to be dying by radiation-induced programmed cell death (apoptosis) while the Raji cells appeared to be dying primarily by classical radiation-induced cellular necrosis. CONCLUSION: We propose that the unusual clinical responsiveness of some high and low grade lymphomas to modest doses of low-dose-rate radioimmunotherapy may be explained in part by the induction of apoptosis. The unusual dose-response characteristics observed in some experimental models of radiation-induced apoptosis may require a reappraisal of standard linear quadratic and alpha/beta algorithms used to predict target tissue cytoreduction after radioimmunotherapy.

Animals↗
PubMed1993

Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody.

BACKGROUND: Many patients with non-Hodgkin's lymphomas are not cured by current therapies, and new approaches to treatment are needed. As part of an ongoing phase 1 study, we examined the effect of radioimmunotherapy with 131I-labeled B-cell-specific anti-CD20 monoclonal antibody in 10 patients with CD20-positive B-cell lymphomas in whom primary chemotherapy had failed. METHODS AND RESULTS: Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with 131I (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, without pretreatment with unlabeled anti-B1 antibody, to all 10 patients; then, with pretreatment with 135 mg of unlabeled antibody, to 8 patients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactivity were obtained after each tracer dose. All known disease sites larger than 2 cm could be imaged. The effect of a pretreatment dose of unlabeled anti-B1 antibody on targeting of the tumor with the radiolabeled antibody was variable. The pretreatment dose of unlabeled antibody that produced the highest ratio of the tumor dose to the whole-body dose in tracer studies was then used to deliver higher doses of radioactivity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treated twice, six to eight weeks apart), four patients received 35 cGy (one patient treated twice), and two patients received 45 cGy (one patient treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients with bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objective responses to tracer infusions before they received radioimmunotherapeutic doses. Of the four patients with complete remissions, one remained in remission for eight months and the other three continue to have no disease progression (for 11, 9, and 8 months). There was mild or no myelosuppression. CONCLUSIONS: Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.

Adult↗
PubMedDate not supplied

Experimental radioimmunotherapy.

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Time-dose-fractionation in radioimmunotherapy: implications for selecting radionuclides.

As currently practiced, the doses delivered to tumors in radioimmunotherapy are less than desirable primarily because of dose-limiting bone marrow toxicity, thus reducing the therapeutic efficacy of this modality. The biological effectiveness of internal radionuclide therapy depends on the total dose, the rate at which it is delivered, and the fractionation schedule of the radiolabeled antibodies administered. A new approach, based on time-dose-fractionation (TDF), which has been used in conventional radiotherapy, is advanced. This approach incorporates differences in dose rates, biological half-lives of the antibodies, physical half-lives of the radionuclides employed and the total doses needed for a given biological effect. The TDF concept is illustrated with several relevant examples for radioimmunotherapy. Based on the TDF approach, it is proposed that under certain biological conditions radionuclides with physical half-lives that are 1-3 times the biological half-life of the radiolabeled antibodies in the tumor are more likely to deliver sterilization doses to tumors than the shorter-lived nuclides presently in use unless precluded by specific activity considerations. Several radionuclides that meet this criteria are suggested with 32P being the most promising among them. Finally, a practical method for treatment planning in radioimmunotherapy using TDF factors is recommended.

Dose-Response Relationship, Radiation↗
PubMed1991

Radioimmunotherapy of B-cell lymphoma.

Radioimmunotherapy has evolved from an attractive concept to implementation in clinical trials for evaluation of toxicity and efficacy. Non-Hodgkin's lymphoma is a useful setting for evaluation of this novel form of therapy. Groups investigating radioimmunotherapy for non-Hodgkin's lymphoma are implementing single high doses and multiple smaller doses of beta emitters I-131 and Y-90 attached to antibodies. All groups giving multiple small doses observe partial responses to treatment with variable hematopoietic toxicity. Single very high doses have yielded complete responses with hematologic toxicity requiring reinfusion of stored bone marrow. A review of radioimmunotherapy trials for non-Hodgkin's lymphoma with a discussion of pertinent related issues is presented.

Antibodies, Monoclonal↗
PubMed1991

186Re radioimmunotherapy of small cell lung carcinoma xenografts in nude mice.

A 186Re-labeled monoclonal antibody (MAb), NR-LU-10, was used for the radioimmunotherapy of a subcutaneous human small cell lung carcinoma xenograft, SHT-1, in nude mice. Biodistribution with specific and irrelevant labeled MAb demonstrated peak tumor uptake of 8% and 3% of the injected dose/g at 2 days, respectively. Dosimetry analysis predicted tumor:whole-body radiation-absorbed dose ratios of 2.43:1 for NR-LU-10 and 0.62:1 for irrelevant MAb. Single-dose toxicity screening estimated a 50% lethal dose within 30 days of 600 microCi (880 cGy of whole-body radiation). As anticipated, a multiple-dose regimen of 490 microCi in four doses over 10 days (720 cGy of whole-body radiation, eight of eight surviving greater than 30 days) was less toxic than a single bolus dose of 430 microCi (644 cGy of whole-body radiation), six of eight surviving greater than 30 days). A multidose radioimmunotherapy regimen was initiated in nude mice bearing 66-mm3 tumors (total dose, 500 to 600 microCi). Complete remissions (greater than 140 days) were achieved in three of 16 mice, and the remainder showed a mean tumor growth delay of 53 days. Matched doses with irrelevant MAb produced one remission, one treatment-related death, and a mean growth delay of only 20 days in six of eight mice. Thus, in this nonoptimal radioimmunotherapy model, significant antitumor responses were observed using a mildly toxic multiple dosing regimen.

Animals↗