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51. Data from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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52. Supplementary Figure 1 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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53. Supplementary Figures 1-4 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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54. Supplementary Tables 1-5 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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55. Supplementary Figure 2 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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56. Supplementary Figure 3 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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57. Supplementary Figure 2 from Targeted Elimination of Prostate Cancer by Genetically Directed Human T Lymphocytes

Author

Gade, Terence P.F., primary, Hassen, Waleed, primary, Santos, Elmer, primary, Gunset, Gertrude, primary, Saudemont, Aurore, primary, Gong, Michael C., primary, Brentjens, Renier, primary, Zhong, Xiao-Song, primary, Stephan, Matthias, primary, Stefanski, Jolanta, primary, Lyddane, Clay, primary, Osborne, Joseph R., primary, Buchanan, Ian M., primary, Hall, Simon J., primary, Heston, Warren D., primary, Rivière, Isabelle, primary, Larson, Steven M., primary, Koutcher, Jason A., primary, and Sadelain, Michel, primary

Published
2023
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58. Supplementary Figure Legends 1-4, Methods from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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59. Supplementary Figure 4 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers

Author

Palaskas, Nicolaos, primary, Larson, Steven M., primary, Schultz, Nikolaus, primary, Komisopoulou, Evangelia, primary, Wong, Justin, primary, Rohle, Dan, primary, Campos, Carl, primary, Yannuzzi, Nicolas, primary, Osborne, Joseph R., primary, Linkov, Irina, primary, Kastenhuber, Edward R., primary, Taschereau, Richard, primary, Plaisier, Seema B., primary, Tran, Chris, primary, Heguy, Adriana, primary, Wu, Hong, primary, Sander, Chris, primary, Phelps, Michael E., primary, Brennan, Cameron, primary, Port, Elisa, primary, Huse, Jason T., primary, Graeber, Thomas G., primary, and Mellinghoff, Ingo K., primary

Published
2023
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60. Supplementary Figure 1 from Targeted Elimination of Prostate Cancer by Genetically Directed Human T Lymphocytes

Author

Gade, Terence P.F., primary, Hassen, Waleed, primary, Santos, Elmer, primary, Gunset, Gertrude, primary, Saudemont, Aurore, primary, Gong, Michael C., primary, Brentjens, Renier, primary, Zhong, Xiao-Song, primary, Stephan, Matthias, primary, Stefanski, Jolanta, primary, Lyddane, Clay, primary, Osborne, Joseph R., primary, Buchanan, Ian M., primary, Hall, Simon J., primary, Heston, Warren D., primary, Rivière, Isabelle, primary, Larson, Steven M., primary, Koutcher, Jason A., primary, and Sadelain, Michel, primary

Published
2023
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61. STARLITE 2: Phase 2 study of nivolumab plus 177lutetium-labeled anti–carbonic anhydrase IX (CAIX) monoclonal antibody girentuximab (177Lu-girentuximab) in patients (pts) with advanced clear cell renal cell carcinoma (ccRCC).

Author

Feldman, Darren R., primary, Motzer, Robert J., additional, Knezevic, Andrea, additional, Lee, Chung-Han, additional, Voss, Martin H, additional, Lyashchenko, Serge K., additional, Park, Hijin, additional, Larson, Steven M., additional, and Pandit-Taskar, Neeta, additional

Published
2023
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65. Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response

Author

Storey, Claire M., primary, Altai, Mohamed, additional, Bicak, Mesude, additional, Veach, Darren R., additional, Lückerath, Katharina, additional, Adrian, Gabriel, additional, McDevitt, Michael R., additional, Kalidindi, Teja, additional, Park, Julie E., additional, Herrmann, Ken, additional, Abou, Diane, additional, Zedan, Wahed, additional, Peekhaus, Norbert, additional, Klein, Robert J., additional, Damoiseaux, Robert, additional, Larson, Steven M., additional, Lilja, Hans, additional, Thorek, Daniel, additional, and Ulmert, David, additional

Published
2023
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66. Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications

Author

Kurtz, Keifer, primary, Eibler, Laura, additional, Dacek, Megan M., additional, Carter, Lukas M., additional, Veach, Darren R., additional, Lovibond, Samantha, additional, Reynaud, Emma, additional, Qureshy, Sarah, additional, McDevitt, Michael R., additional, Bourne, Christopher, additional, Monette, Sebastien, additional, Punzalan, Blesida, additional, Khayat, Shireen, additional, Verma, Svena, additional, Kesner, Adam L., additional, Cheung, Nai-Kong V., additional, Schöder, Heiko, additional, Gajecki, Leah, additional, Cheal, Sarah M., additional, Larson, Steven M., additional, Scheinberg, David A., additional, and Krebs, Simone, additional

Published
2023
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68. Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma (HCC)

Author

Abou-Alfa, Ghassan K., Yen, Chia-Jui, Hsu, Chih-Hung, O’Donoghue, Joseph, Beylergil, Volkan, Ruan, Shutian, Pandit-Taskar, Neeta, Gansukh, Bolorsukh, Lyashchenko, Serge K., Ma, Jennifer, Wan, Peter, Shao, Yu-Yun, Lin, Zhong-Zhe, Frenette, Catherine, O’Neil, Bert, Schwartz, Lawrence, Smith-Jones, Peter M., Ohtomo, Toshihiko, Tanaka, Takayoshi, Morikawa, Hideo, Maki, Yuko, Ohishi, Norihisa, Chen, Ya-Chi, Agajanov, Tamara, Boisserie, Frederic, Di Laurenzio, Laura, Lee, Ray, Larson, Steven M., Cheng, Ann-Lii, and Carrasquilo, Jorge A.

Published
2017
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69. Sustained ERK inhibition maximizes responses of [Braf.sup.V600E] thyroid cancers to radioiodine

Author

Nagarajah, James, Le, Mina, Knauf, Jeffrey A., Ferrandino, Giuseppe, Montero-Conde, Cristina, Pillarsetty, Nagavarakishore, Bolaender, Alexander, Irwin, Christopher, Krishnamoorthy, Gnana Prakasam, Saqcena, Mahesh, Larson, Steven M., Ho, Alan L., Seshan, Venkatraman, Ishii, Nobuya, Carrasco, Nancy, Rosen, Neal, Weber, Wolfgang A., and Fagin, James A.

Subjects
Gene mutations -- Analysis, Thyroid cancer -- Care and treatment, Radiotherapy -- Usage, Health care industry
Abstract

Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with [Braf.sup.V600E]-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer., Introduction Effective radioiodide (RAI) therapy of metastatic thyroid cancers requires uptake of RAI via the sodium/iodide symporter (NIS), and optimally, its incorporation into tyrosine residues of thyroglobulin (TG) to increase [...]

Published
2016
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73. Positron Emission Tomography/Computed Tomography–Based Assessments of Androgen Receptor Expression and Glycolytic Activity as a Prognostic Biomarker for Metastatic Castration-Resistant Prostate Cancer

Author

Fox, Josef J., Gavane, Somali C., Blanc-Autran, Estelle, Nehmeh, Sadek, Gönen, Mithat, Beattie, Brad, Vargas, Hebert A., Schöder, Heiko, Humm, John L., Fine, Samson W., Lewis, Jason S., Solomon, Stephen B., Osborne, Joseph R., Veach, Darren, Sawyers, Charles L., Weber, Wolfgang A., Scher, Howard I., Morris, Michael J., and Larson, Steven M.

Published
2018
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75. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity 86Y- or 177Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

Author

Cheal, Sarah M., Xu, Hong, Guo, Hong-fen, Lee, Sang-gyu, Punzalan, Blesida, Chalasani, Sandhya, Fung, Edward K., Jungbluth, Achim, Zanzonico, Pat B., Carrasquillo, Jorge A., O’Donoghue, Joseph, Smith-Jones, Peter M., Wittrup, K. Dane, Cheung, Nai-Kong V., and Larson, Steven M.

Published
2016
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77. Assessing Functional Androgen Receptor Pathway Activity in Response to Radiotherapy Using hK2-targeted PET Imaging

Author

Storey, Claire M., primary, Altai, Mohamed, additional, Bicak, Mesude, additional, Veach, Darren R., additional, Lueckerath, Katharina, additional, Adrian, Gabriel, additional, McDevitt, Michael R., additional, Kalidindi, Teja, additional, Park, Julie E., additional, Herrmann, Ken, additional, Abou, Diane, additional, Zedan, Wahed, additional, Peekhaus, Norbert, additional, Klein, Robert J., additional, Damoiseaux, Robert, additional, Larson, Steven M., additional, Lilija, Hans, additional, Thorek, Daniel, additional, Thorek, Daniel LJ, additional, and Ulmert, David, additional

Published
2022
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78. Abstract 3309: Self-assembling and disassembling (SADA) domain is critical to the binding, and anti-tumor efficacy of GD2-SADA

Author

Santich, Brian H., primary, Kjellev, Stine Louise, additional, Cheal, Sarah, additional, Wang, Linlin, additional, Gillberg, Mette, additional, Vadlamudi, Mallika, additional, Ouattara, Amadou A., additional, Liebenberg, Nico, additional, Larsen, Lone Frost, additional, Veach, Darren R., additional, Seo, Shin, additional, Cheung, Nai-Kong V., additional, Larson, Steven M., additional, and Lisby, Steen, additional

Published
2022
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79. STARLITE 2: Phase 2 study of nivolumab plus 177Lutetium-labeled anti-carbonic anhydrase IX (CAIX) monoclonal antibody girentuximab (177Lu-girentuximab) in patients (pts) with advanced clear cell renal cell carcinoma (ccRCC).

Author

Feldman, Darren R., primary, Motzer, Robert J., additional, Knezevic, Andrea, additional, Lee, Chung-Han, additional, Voss, Martin H, additional, Lyashchenko, Serge K., additional, Park, Hijin, additional, Larson, Steven M., additional, and Pandit-Taskar, Neeta, additional

Published
2022
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80. Phase 2 of trametinib plus radioiodine in RAS-mutant and wild-type, radioiodine-refractory thyroid cancer (ETCTN9446).

Author

Burman, Bharat, primary, Tuttle, R. Michael, additional, Grewal, Ravinder K, additional, Sherman, Eric Jeffrey, additional, Baxi, Shrujal S., additional, Boucai, Laura, additional, Sabra, Mona, additional, Fish, Stephanie, additional, Pentlow, Keith S., additional, Haque, Sofia, additional, Ostrovnaya, Irina, additional, Ghossein, Ronald A, additional, Chen, Helen X., additional, Humm, John, additional, Carducci, Michael Anthony, additional, Larson, Steven M., additional, Pfister, David G., additional, Fagin, James A, additional, and Ho, Alan Loh, additional

Published
2022
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82. PET-based compartmental modeling of 124I-A33 antibody: quantitative characterization of patient-specific tumor targeting in colorectal cancer

Author

Zanzonico, Pat, Carrasquillo, Jorge A., Pandit-Taskar, Neeta, O’Donoghue, Joseph A., Humm, John L., Smith-Jones, Peter, Ruan, Shutian, Divgi, Chaitanya, Scott, Andrew M., Kemeny, Nancy E., Fong, Yuman, Wong, Douglas, Scheinberg, David, Ritter, Gerd, Jungbluth, Achem, Old, Lloyd J., and Larson, Steven M.

Published
2015
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84. Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab

Author

Rosenblat, Todd L., primary, McDevitt, Michael R., additional, Carrasquillo, Jorge A., additional, Pandit-Taskar, Neeta, additional, Frattini, Mark G., additional, Maslak, Peter G., additional, Park, Jae H., additional, Douer, Dan, additional, Cicic, Dragan, additional, Larson, Steven M., additional, Scheinberg, David A., additional, and Jurcic, Joseph G., additional

Published
2022
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85. Enhancing Radioiodine Incorporation in BRAF-Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial

Author

Tchekmedyian, Vatche, primary, Dunn, Lara, additional, Sherman, Eric, additional, Baxi, Shrujal S., additional, Grewal, Ravinder K., additional, Larson, Steven M., additional, Pentlow, Keith S., additional, Haque, Sofia, additional, Tuttle, R. Michael, additional, Sabra, Mona M., additional, Fish, Stephanie, additional, Boucai, Laura, additional, Walters, Jamie, additional, Ghossein, Ronald A., additional, Seshan, Venkatraman E., additional, Knauf, Jeffrey A., additional, Pfister, David G., additional, Fagin, James A., additional, and Ho, Alan L., additional

Published
2022
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86. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

Author

Pandit-Taskar, Neeta, O’Donoghue, Joseph A., Beylergil, Volkan, Lyashchenko, Serge, Ruan, Shutian, Solomon, Stephen B., Durack, Jeremy C., Carrasquillo, Jorge A., Lefkowitz, Robert A., Gonen, Mithat, Lewis, Jason S., Holland, Jason P., Cheal, Sarah M., Reuter, Victor E., Osborne, Joseph R., Loda, Massimo F., Smith-Jones, Peter M., Weber, Wolfgang A., Bander, Neil H., Scher, Howard I., Morris, Michael J., and Larson, Steven M.

Published
2014
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90. Additional file 3 of Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies

Author

Kramer, Kim, Pandit-Taskar, Neeta, Kushner, Brian H., Zanzonico, Pat, Humm, John L., Tomlinson, Ursula, Donzelli, Maria, Wolden, Suzanne L., Haque, Sophia, Dunkel, Ira, Souweidane, Mark M., Greenfield, Jeffrey P., Tickoo, Satish, Lewis, Jason S., Lyashchenko, Serge K., Carrasquillo, Jorge A., Chu, Bae, Horan, Christopher, Larson, Steven M., Cheung, Nai-Kong V., and Modak, Shakeel

Abstract

Additional file 3. Tables S1–S4.

Published
2022
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91. Additional file 1 of Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies

Author

Kramer, Kim, Pandit-Taskar, Neeta, Kushner, Brian H., Zanzonico, Pat, Humm, John L., Tomlinson, Ursula, Donzelli, Maria, Wolden, Suzanne L., Haque, Sophia, Dunkel, Ira, Souweidane, Mark M., Greenfield, Jeffrey P., Tickoo, Satish, Lewis, Jason S., Lyashchenko, Serge K., Carrasquillo, Jorge A., Chu, Bae, Horan, Christopher, Larson, Steven M., Cheung, Nai-Kong V., and Modak, Shakeel

Abstract

Additional file 1. Figure S1. Consort diagram.

Published
2022
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94. Intraperitoneal Pretargeted Radioimmunotherapy for Colorectal Peritoneal Carcinomatosis

Author

Chandler, Christopher S., primary, Bell, Meghan M., additional, Chung, Sebastian K., additional, Veach, Darren R., additional, Fung, Edward K., additional, Punzalan, Blesida, additional, Burnes Vargas, Daniela, additional, Patel, Mitesh, additional, Xu, Hong, additional, Guo, Hong-fen, additional, Santich, Brian H., additional, Zanzonico, Pat B., additional, Monette, Sébastien, additional, Nash, Garrett M., additional, Cercek, Andrea, additional, Jungbluth, Achim, additional, Pandit-Taskar, Neeta, additional, Cheung, Nai Kong V., additional, Larson, Steven M., additional, and Cheal, Sarah M., additional

Published
2022
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96. Abstract P168: Pretargeted radioimmunotherapy using 225Ac for intraperitoneal Her2-expressing epithelial ovarian carcinoma xenografts

Author

Chung, Sebastian K., primary, Chandler, Christopher S., additional, Vargas, Daniela Burnes, additional, Seo, Shin H., additional, McDevitt, Michael R., additional, Veach, Darren, additional, Punzalan, Blesida, additional, Hong, Xu, additional, Guo, Hong-fen, additional, Nash, Garrett M., additional, Cercek, Andrea, additional, Cheung, Nai-Kong V., additional, Larson, Steven M., additional, and Cheal, Sarah M., additional

Published
2021
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97. Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies.

Author

Kramer, Kim, Pandit-Taskar, Neeta, Kushner, Brian H., Zanzonico, Pat, Humm, John L., Tomlinson, Ursula, Donzelli, Maria, Wolden, Suzanne L., Haque, Sophia, Dunkel, Ira, Souweidane, Mark M., Greenfield, Jeffrey P., Tickoo, Satish, Lewis, Jason S., Lyashchenko, Serge K., Carrasquillo, Jorge A., Chu, Bae, Horan, Christopher, Larson, Steven M., and Cheung, Nai-Kong V.

Subjects
NEUROBLASTOMA, MEMBRANE glycoproteins, CENTRAL nervous system tumors
Abstract

Background: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies. Patients and methods: We conducted a phase I trial of intraventricular 131I-omburtamab using a standard 3 + 3 design. Eligibility criteria included adequate cerebrospinal fluid (CSF) flow, no major organ toxicity, and for patients > dose level 6, availability of autologous stem cells. Patients initially received 74 MBq radioiodinated omburtamab to evaluate dosimetry and biodistribution followed by therapeutic 131I-omburtamab dose-escalated from 370 to 2960 MBq. Patients were monitored clinically and biochemically for toxicity graded using CTCAEv 3.0. Dosimetry was evaluated using serial CSF and blood sampling, and serial PET or gamma-camera scans. Patients could receive a second cycle in the absence of grade 3/4 non-hematologic toxicity or progressive disease. Results: Thirty-eight patients received 100 radioiodinated omburtamab injections. Diagnoses included metastatic neuroblastoma (n = 16) and other B7H3-expressing solid tumors (n = 22). Thirty-five patients received at least 1 cycle of treatment with both dosimetry and therapy doses. Acute toxicities included < grade 4 self-limited headache, vomiting or fever, and biochemical abnormalities. Grade 3/4 thrombocytopenia was the most common hematologic toxicity. Recommended phase 2 dose was 1850 MBq/injection. The median radiation dose to the CSF and blood by sampling was 1.01 and 0.04 mGy/MBq, respectively, showing a consistently high therapeutic advantage for CSF. Major organ exposure was well below maximum tolerated levels. In patients developing antidrug antibodies, blood clearance, and therefore therapeutic index, was significantly increased. In patients receiving cRIT for neuroblastoma, survival was markedly increased (median PFS 7.5 years) compared to historical data. Conclusions: cRIT with 131I-omburtamab is safe, has favorable dosimetry and may have a therapeutic benefit as adjuvant therapy for B7-H3-expressing leptomeningeal metastases. Trial registration: clinicaltrials.gov NCT00089245, August 5, 2004. [ABSTRACT FROM AUTHOR]

Published
2022
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