Comparison of Radiation Dose Estimation for Myeloablative Radioimmunotherapy for Relapsed or Recurrent Mantle Cell Lymphoma Using<sup>131</sup>I Tositumomab to That of Other Types of Non-Hodgkin's Lymphoma

Rajendran, Joseph G.; Gopal, Ajay K.; Durack, Lawrence D.; Fisher, Darrell R.; Press, Oliver W.; Eary, Janet F.

doi:10.1089/cbr.2004.19.738

Cited by 7 publications

(3 citation statements)

References 32 publications

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“…Novel therapeutic agents are needed in clinical trials. [4][5][6][7][8] Atiprimod (N-N-diethyl-8,8-dipropyl-2-azaspiro [4,5] decane-2-propanamine), a novel cationic amphiphilic compound, has been studied for its anticancer properties in malignancies. [9][10][11] Recent reports have suggested that atiprimod exhibits antiproliferative and antiangiogenic activities, induces apoptosis via activation of caspases-3 and -8, and inhibits phosphorylation of Akt and STAT3 in multiple myeloma (MM).…”

Section: Introductionmentioning

confidence: 99%

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Wang

Zhang

Han

et al. 2007

Blood

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Atiprimod is a novel cationic amphiphilic compound and has been shown to exert antimyeloma effects both in vitro and in mouse experiments. This study was undertaken to evaluate the therapeutic efficacy of atiprimod on mantle cell lymphoma (MCL) and elucidate the mechanism by which it induces cell apoptosis. IntroductionMantle cell lymphoma (MCL) represents approximately 8% of all non-Hodgkin lymphomas (NHLs). It has the worst prognosis among all B-cell-derived malignancies with median survival of 3 to 4 years. [1][2][3] Although MCL has been treated with chemotherapy, radiotherapy, hematopoietic stem cell transplantation, molecular targeted therapy, and combination therapy of these treatments, no standard treatment approach has been established thus far. Novel therapeutic agents are needed in clinical trials. [4][5][6][7][8]5] decane-2-propanamine), a novel cationic amphiphilic compound, has been studied for its anticancer properties in malignancies. [9][10][11] Recent reports have suggested that atiprimod exhibits antiproliferative and antiangiogenic activities, induces apoptosis via activation of caspases-3 and -8, and inhibits phosphorylation of Akt and STAT3 in multiple myeloma (MM). 10,12 In addition, atiprimod exhibits in vivo antimyeloma effects in xenograft severe combined immunodeficient (SCID) mouse models. 10,13 These results provide a framework for clinical trials of atiprimod in MM.MCL has distinct biologic, morphologic, and immunophenotypic features in NHL. 14 MCL responds to similar agents used effectively for MM. For example, the chemotherapy regimens CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and hyperCVAD (cyclophosphamide, vincristine, doxorubicin, decadron, cytarabine, and methotrexate) are effective in B-cell NHL, especially in MCL, 15 but their slight modifications are also effective in MM. [16][17][18][19] Bortezomib, a potent and specific proteasome inhibitor that was U. S. Food and Drug Administration-approved for relapsed MM, was also proven to be effective in MCL. 20 Thalidomide is active in MM, and thalidomide in combination with rituximab induces impressive antitumor activity in relapsed/ refractory MCL patients. 21 Revlimid, an immunomodulatory drug that produces durable clinical responses in patients with relapsed and refractory MM, 22 also is showing activity in clinical trials for treatment of NHL. Thus, we hypothesize that MCL and MM share certain biologic mechanisms in responding to various compound therapies. Atiprimod, which exhibits significant antitumor ability against MM cells by growth inhibition and apoptosis, 10 may also prove effective in MCL. In this study, we demonstrate that atiprimod not only inhibited growth and induced apoptosis of MCL cell lines SP53, MINO, Grant 519, Jeko-1, and freshly isolated patient-derived primary MCL cells in vitro, but it was also therapeutic against established human MCL in xenograft SCID mouse models. Of importance, atiprimod exhibited lower cytotoxicity against normal T cells. Furthermore, we attempted to eluc...

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Section: Introductionmentioning

confidence: 99%

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Wang

Zhang

Han

et al. 2007

Blood

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“…3,4 Yet even from its earliest days, the clinical prospects of RIT have been hampered by a critical complication: high radiation dose rates to healthy tissues. 5,6 Generally speaking, radioimmunoconjugates for RIT are labeled with long-lived radionuclides -e.g. 131 I (t ½ = 8.0 days) and 90 Y (t ½ = 2.7 days) -with physical half-lives that dovetail well with the long pharmacokinetic half-lives of immunoglobulins.…”

Section: Introductionmentioning

confidence: 99%

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

Membreno

Zeglis

2019

JoVE

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While radioimmunotherapy (RIT) is a promising approach for the treatment of cancer, the long pharmacokinetic half-life of radiolabeled antibodies can result in high radiation doses to healthy tissues. Perhaps not surprisingly, several different strategies have been developed to circumvent this troubling limitation. One of the most promising of these approaches is pretargeted radioimmunotherapy (PRIT). PRIT is predicated on decoupling the radionuclide from the immunoglobulin, injecting them separately, and then allowing them to combine in vivo at the target tissue. This approach harnesses the exceptional tumor-targeting properties of antibodies while skirting their pharmacokinetic drawbacks, thereby lowering radiation doses to non-target tissues and facilitating the use of radionuclides with half-lives that are considered too short for use in traditional radioimmunoconjugates. Over the last five years, our laboratory and others have developed an approach to in vivo pretargeting based on the inverse electron-demand Diels-Alder (IEDDA) reaction between trans-cyclooctene (TCO) and tetrazine (Tz). This strategy has been successfully applied to pretargeted positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a variety of antibody-antigen systems. In a pair of recent publications, we have demonstrated the efficacy of IEDDA-based PRIT in murine models of pancreatic ductal adenocarcinoma and colorectal carcinoma. In this protocol, we describe protocols for PRIT using a 177 Lu-DOTA-labeled tetrazine radioligand ([ 177 Lu]Lu-DOTA-PEG 7 -Tz) and a TCO-modified variant of the colorectal cancer targeting huA33 antibody (huA33-TCO). More specifically, we will describe the construction of huA33-TCO, the synthesis and radiolabeling of [ 177 Lu]Lu-DOTA-PEG 7 -Tz, and the performance of in vivo biodistribution and longitudinal therapy studies in murine models of colorectal carcinoma.

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“…In particular, high-dose radioimmunotherapy (RIT) can deliver potentially curative doses of radiation to tumor sites while limiting the relative radiation exposure to non–target organs [2]. Although previous studies have investigated the total absorbed dose and biological effects of high-dose RIT on the critical organs such as liver and lungs [3, 4], little is known of the effects of high-dose therapy on non-critical organs. For male patients, testicular exposure from high-dose RIT is of concern as it may lead to decreased serum testosterone levels, potentially affecting fertility and quality of life after treatment.…”

Section: Introductionmentioning

confidence: 99%

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma

Hattori

Gopal

Shields

et al. 2012

Nuclear Medicine Communications

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Purpose To investigate radiation dose to testes delivered by radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. METHODS Testicular uptake and retention of 131I tositumomab were measured and testicular absorbed doses were calculated for 67 male patients (54 ± 11 years old) with non-Hodgkin lymphoma who underwent myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging. In a subset of patients, male sex hormones were measured before and one year after the therapy. RESULTS Absorbed dose to testes showed considerable variability (range = 4.4 to 70.2 Gy). Pre-therapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction (4.6 ± 1.8 nmol/L (pre-RIT) vs. 3.8 ± 2.9 nmol/L (post-RIT), p < 0.05). Patients receiving higher radiation doses to the testes (≥ 25 Gy) showed a greater reduction (4.7 ± 1.6 nmol/L (pre RIT) vs. 3.3 ± 2.7 nmol/L (post-RIT), p < 0.05) than did patients receiving lower doses (< 25 Gy), who showed no significant change in total testosterone levels. CONCLUSION The testicular radiation absorbed dose varied highly among individual patients. Patients receiving higher doses to testes were more likely to show post-RIT suppression of testosterone levels.

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Comparison of Radiation Dose Estimation for Myeloablative Radioimmunotherapy for Relapsed or Recurrent Mantle Cell Lymphoma Using¹³¹I Tositumomab to That of Other Types of Non-Hodgkin's Lymphoma

Abstract: Myeloablative RIT using (131)I tositumomab results in normal organ radiation-absorbed doses similar to those in patients with other non-Hodgkin's lymphoma, and is suitable for treating patients with relapsed or refractory MCL.

Cited by 7 publications

References 32 publications

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma

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Comparison of Radiation Dose Estimation for Myeloablative Radioimmunotherapy for Relapsed or Recurrent Mantle Cell Lymphoma Using131I Tositumomab to That of Other Types of Non-Hodgkin's Lymphoma

Abstract: Myeloablative RIT using (131)I tositumomab results in normal organ radiation-absorbed doses similar to those in patients with other non-Hodgkin's lymphoma, and is suitable for treating patients with relapsed or refractory MCL.

Cited by 7 publications

References 32 publications

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma

Contact Info

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Comparison of Radiation Dose Estimation for Myeloablative Radioimmunotherapy for Relapsed or Recurrent Mantle Cell Lymphoma Using¹³¹I Tositumomab to That of Other Types of Non-Hodgkin's Lymphoma