Dosimetric comparison of radionuclides for therapy of somatostatin receptor-expressing tumors

Bernhardt, Peter; Benjegård, S. A.; Kölby, Lars; Johanson, Viktor; Nilsson, Ola; Ahlman, Håkan; Forssell-Aronsson, Eva

doi:10.1016/s0360-3016(01)01663-7

Cited by 49 publications

(44 citation statements)

References 16 publications

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“…The low-energy β-emission makes it particularly suitable for imaging small or diffusely infiltrating tumours which are often found in NHL patients, since a lower energy β-emission results in a more favourable tumour to non-tumour ratio than higher energy β-emission [19,20]. For example, the energy of the 90 Y β-radiation might be too high for these tumours.…”

Section: Discussionmentioning

confidence: 99%

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

Forrer

Chen

Fani

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose 131I-and 90 Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either 177 Lu or 90 Y. Materials and methods Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. ResultsThe immunological binding properties of DOTArituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10 5 times excess of diethylenetriaminepentaacetic acid (DTPA, 37°C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m 2 body surface 177 Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of 177 Lu-DOTArituximab was tolerated well. Conclusion Our results show that DOTA-rituximab (4:1) can be labelled with 177 Lu with sufficient stability while the immunoconjugate retains its immunoreactivity.177 Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL.

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Section: Discussionmentioning

confidence: 99%

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

Forrer

Chen

Fani

et al. 2009

Eur J Nucl Med Mol Imaging

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“…We have selected the low-energy h emitter 177 Lu, which has a spectrum of emitted h energies suitable for targeting of micrometastases (14,15). The CHX-pertuzumab complex gives a chelate-mediated binding of 177 Lu.…”

Section: Introductionmentioning

confidence: 99%

[177Lu]Pertuzumab: Experimental Therapy of HER-2–Expressing Xenografts

Persson¹,

Gedda²,

Lundqvist³

et al. 2007

Cancer Research

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Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy B emitter 177 Lu, might be a candidate for targeted radiotherapy of disseminated HER-2-positive micrometastases. The radiolabeled antibody [177 Lu]pertuzumab showed favorable targeting properties in BALB/c (nu/nu) mice with HER-2-overexpressing xenografts. The absorbed dose in tumors was more than five times higher than the absorbed dose in blood and more than seven times the absorbed dose in any other normal organ. Experimental therapy showed that [177 Lu]pertuzumab delayed tumor progression compared with controls (no treatment, P < 0.0001; nonlabeled pertuzumab antibody, P < 0.0001; and 177 Lu-labeled irrelevant antibody, P < 0.01

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“…177 Lu is a low-energy b-emitter (maximum energy, 0.497 MeV) with a relatively short tissue penetration range (maximum, 1.6 mm). Because malignant lymphoma cells often infiltrate normal tissues in a diffuse manner, we decided to use the lower b-energy and shorter tissue penetration of 177 Lu as these may result in a more favorable tumor-to-nontumor ratio (16,17). In addition, 177 Lu emits g-radiation (113 keV, 7%; 208 keV, 11%) that can be used for scintigraphic imaging, allowing immediate control of distribution and dosimetry in treated patients.…”

mentioning

confidence: 99%

Radioimmunotherapy with ¹⁷⁷Lu-DOTA-Rituximab: Final Results of a Phase I/II Study in 31 Patients with Relapsing Follicular, Mantle Cell, and Other Indolent B-Cell Lymphomas

et al. 2013

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The aim of this study was to determine the maximum tolerated dose (MTD) and to explore the clinical response to 177 Lu-DOTA-rituximab in the treatment of patients with relapsed follicular, mantle cell, or other indolent lymphomas such as marginal zone lymphoma. Methods: To evaluate the MTD, we adjusted the dosage of the radiopharmaceutical according to body surface area (BSA). Results: The MTD using 177 Lu-DOTA-rituximab was 1,665 MBq/m 2 of BSA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. Significant anemia occurred only at dose level 7 (1,850 MBq/m 2 of BSA). We observed the nadir of platelets after a median of 36 d from treatment and the nadir of granulocytes after a median of 50 d. Median time to recovery to the next lower grade of toxicity was 7 d. Nonhematologic toxicity was negligible. We observed clinical responses at all dose levels and for all lymphoma entities. Some of the responses were durable; the longest follow-up is currently over 8 y. At present, 11 patients are alive and 8 patients are disease-free. Conclusion: Our results demonstrate the safety and feasibility of 177 Lu-DOTA-rituximab treatment for the lymphoma entities tested in this study.

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Dosimetric comparison of radionuclides for therapy of somatostatin receptor-expressing tumors

Cited by 49 publications

References 16 publications

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

[177Lu]Pertuzumab: Experimental Therapy of HER-2–Expressing Xenografts

Radioimmunotherapy with ¹⁷⁷Lu-DOTA-Rituximab: Final Results of a Phase I/II Study in 31 Patients with Relapsing Follicular, Mantle Cell, and Other Indolent B-Cell Lymphomas

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Dosimetric comparison of radionuclides for therapy of somatostatin receptor-expressing tumors

Cited by 49 publications

References 16 publications

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

[177Lu]Pertuzumab: Experimental Therapy of HER-2–Expressing Xenografts

Radioimmunotherapy with 177Lu-DOTA-Rituximab: Final Results of a Phase I/II Study in 31 Patients with Relapsing Follicular, Mantle Cell, and Other Indolent B-Cell Lymphomas

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Radioimmunotherapy with ¹⁷⁷Lu-DOTA-Rituximab: Final Results of a Phase I/II Study in 31 Patients with Relapsing Follicular, Mantle Cell, and Other Indolent B-Cell Lymphomas