Treatment of lung tumor colonies with 90Y targeted to blood vessels: comparison with the α-particle emitter 213Bi

Kennel, Stephen J.; Stabin, Michael G.; Yoriyaz, Hélio; Brechbiel, Martin W.; Mirzadeh, Saed

doi:10.1016/s0969-8051(98)00069-9

Cited by 22 publications

(20 citation statements)

References 20 publications

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“…Preclinical and clinical studies have shown the promise of a-particle radioimmunotherapy in non-Hodgkin's lymphoma (27), leukemia (28,29), disseminated peritoneal (14,30), and lung diseases (16). In breast cancer, the most frequent sites of metastatic progression are the bone, lung, and liver; these are found to harbor metastases in over 50% of breast cancer patients; more widely disseminated disease is commonly observed in f45% of the patients (31).…”

Section: Discussionmentioning

confidence: 99%

“…In three mouse models of intraperitoneal metastases of colon, pancreatic, and stomach cancer, 213 Bi-labeled antibodies have been able to improve survival rates in these mice (14,15). Efficacy of 213 Bi-labeled antibodies to target lung metastases and melanoma have also been shown (16,17). Clinical trials have shown safety, feasibility, and imaging of 213 Bi-labeled anti-CD33 antibody localization in targeting myeloid leukemia (18,19).…”

Section: Introductionmentioning

confidence: 99%

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213Bi (α-Emitter)–Antibody Targeting of Breast Cancer Metastases in theneu-N Transgenic Mouse Model

Song¹,

Shahverdi²,

Huso³

et al. 2008

Cancer Research

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Treatment failure in breast cancer is largely the failure to control metastatic dissemination. In this study, we investigated the efficacy of an antibody against the rat variant of HER-2/neu, labeled with the A-particle emitter 213 Bi to treat widespread metastases in a rat/neu transgenic mouse model of metastatic mammary carcinoma. The model manifests wide-spread dissemination of tumor cells leading to osteolytic bone lesions and liver metastases, common sites of clinical metastases. The maximum tolerated dose was 120 MCi of 213 Bi-7.16.4. The kinetics of marrow suppression and subsequent recovery were determined. Three days after left cardiac ventricular injection of 10 5 rat HER-2/neu-expressing syngeneic tumor cells, neu-N mice were treated with (a) 120 MCi 213 (b) .4 increased median survival time to 41 days compared with 28 days for the untreated controls (P < 0.0001); corresponding median survival times for groups b, c, and d were 36 (P < 0.001), 31 (P < 0.01), and 33 (P = 0.05) days, respectively. Median survival relative to controls was not significantly improved in mice injected with 10-fold less cells or with multiple courses of treatment. We concluded that A-emitter 213 Bi-labeled monoclonal antibody targeting the HER-2/neu antigen was effective in treating early-stage HER-2/neu-expressing micrometastases. Analysis of the results suggests that further gains in efficacy may require higher specific activity constructs or target antigens that are more highly expressed on tumor cells. [Cancer Res 2008;68(10):3873-80]

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

213Bi (α-Emitter)–Antibody Targeting of Breast Cancer Metastases in theneu-N Transgenic Mouse Model

Song¹,

Shahverdi²,

Huso³

et al. 2008

Cancer Research

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“…8 Only a few preclinical studies have compared the efficacy and toxicity of ␤ and ␣ emitters in a mouse model, and they demonstrated a favorable profile for 213 Bi compared with yttrium 90 ( 90 Y). 44,45 Despite these advantages, there are certain limitations to the use of 213 Bi, particularly its limited availability and high cost. Also, its short t 1/2 makes its use logistically challenging.…”

Section: Org Frommentioning

confidence: 99%

“…In previous studies, DTPA chelates that incorporated a CHX group in their structure produced conjugates that were labeled rapidly and were resistant to release of radiobismuth in vivo. 45,[50][51][52] Because of these results, we chose to use the CHX-AЉ-DTPA 22 conjugate for our studies. Reliable and stable labeling of mAbs with indium 111, 90 Y, 212 Bi, and 213 Bi can be performed by using the CHX-AЉ-DTPA chelator.…”

Section: Org Frommentioning

confidence: 99%

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Bismuth 213–labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

Sandmaier

Bethge

Wilbur

et al. 2002

Blood

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To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external-beam ␥ irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (half-life, 46 minutes) ␣-emitter bismuth 213 ( 213 Bi) conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a doseescalation study, 7 dogs treated with the 213 Bi-anti-CD45 conjugate ( 213 Bi dose, 0.1-5.9 mCi/kg [3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg 213 Bilabeled anti-CD45 mAb ( 213 Bi doses, 3.6, 4.6, and 8.8 mCi/kg [133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLAidentical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). The therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs had prompt engraftment and achieved stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results will form the basis for additional studies in animals and later the design of clinical trials using 213 IntroductionAllogeneic marrow transplantation provides a potential cure for a variety of hematologic and nonhematologic diseases. To avoid mortality and toxic effects associated with myeloablative marrow transplantation, a nonmyeloablative marrow transplantation regimen was developed in a canine model. The regimen uses 200 cGy total-body irradiation (TBI) before and administration of mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for immunosuppression after transplantation. 1 The combination of MMF and CSP given after transplantation controlled not only graft-versus-host disease (GVHD) but was also found to be essential for maintenance of the donor graft (ie, control of host-versus-graft reaction). The results of the preclinical studies have been successfully translated into the clinic to treat elderly or medically infirm patients with hematologic malignant diseases who were not eligible to receive high-dose conventional grafts. 2 Although the TBI dose used in these studies was low, there remains concern about the possible late toxic effects of ␥ radiation, especially in patients given transplan...

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Cancer radioimmunotherapy with alpha-emitting nuclides

Couturier

Supiot

Degraef-Mougin

et al. 2005

Eur J Nucl Med Mol Imaging

153

111

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In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

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Treatment of lung tumor colonies with 90Y targeted to blood vessels: comparison with the α-particle emitter 213Bi

Cited by 22 publications

References 20 publications

213Bi (α-Emitter)–Antibody Targeting of Breast Cancer Metastases in theneu-N Transgenic Mouse Model

213Bi (α-Emitter)–Antibody Targeting of Breast Cancer Metastases in theneu-N Transgenic Mouse Model

Bismuth 213–labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

Cancer radioimmunotherapy with alpha-emitting nuclides

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