131-I-MIBG and Targeted Therapy for Neuroblastoma: Infrastructure Proposal.

Project Goal
The goal of this project is for the Pediatric Oncology Neuroblastoma Research Program at UCSF Children’s Hospital to expand its research capabilities, continue to develop collaborative research projects, recruit additional staff members, and advance its clinical research capacity. These efforts are all undertaken to improve both the current and future treatment of patients with neuroblastoma, with a goal of ultimately removing the threat of this disease.

Our work at UCSF falls into several categories:

1. Continued progress in targeted radiotherapy to neuroblastoma with 131I-MIBG
2. Leadership in the NANT consortium for testing of novel drugs to treat advanced neuroblastoma
3. Collaboration with laboratory scientists at UCSF in molecular mechanisms of neuroblastoma and new therapy development
4. National collaborations and leadership in therapy and molecular mechanisms of neuroblastoma through the Children’s Oncology Group.

Next Steps
In the coming year, we have initiated a new study using ¹²⁴I-MIBG PET scans to assess pre-therapy dosimetry and increase sensitivity of MIBG scans. We are also poised to open our new NANT randomized Phase II study of ¹³¹I-MIBG compared to MIBG combined with radiosensitizers. We will continue our pre-clinical studies of MIBG in combination with other biologic agents.

Publications

Mueller S, Bhargava S, Yang X, Kolkowitz I, Olow A, Wehmeijer N, Gragg A, Orbach S, Cheng J, Weiss WA, Matthay KK, Haas-Kogan DA. Poly (ADP-Ribose) Polymerase inhibitor MK-4827 in combination with radiation as a novel therapy for metastatic neuroblastoma. Anticancer Res 2013; 33:755-62.

Wong T, Matthay KK, Boscardin J, Hawkins RA, Brakeman PR, DuBois SG. Acute changes in blood pressure in patients with neuroblastoma treated with ¹³¹I-metaiodobanzylguandidne (MIBG). Pediatr Blood Cancer 2013; 60:1424-30. Apr 23 [Epub ahead of print] PMID:23613447

DuBois SG, Matthay KK. 131I-Metaiodobenzylguanidine therapy in children with advanced neuroblastoma. Q J Nucl Med Mol Imaging. 2013 Mar;57(1):53-65. Review.

French S, Dubois SG, Horn B, Granger M, Hawkins R, Pass A, Plummer E, Matthay K. ¹³¹I-MIBG followed by Consolidation with Busulfan, Melphalan and Autologous Stem Cell Transplantation for Refractory Neuroblastoma. Pediatr Blood Cancer 2012; 60:879-884. Epub 2012 Sep 28.PMID: 23024113

Dubois SG, Geier E, Batra V, Yee SW, Neuhaus J, Segal M, Martinez D, Pawel B, Yanik G, Naranjo A, London WB, Kreissman S, Baker D, Attiyeh E, Hogarty MD, Maris JM, Giacomini K, Matthay KK. Evaluation of norepinephrine transporter expression and metaiodobenzylguanidine (MIBG) avidity in neuroblastoma: A Report from the Children’s Oncology Group. Int J Mol Im 2012; 2012:250834. doi: 10.1155,Epub 2012 Sep 25.

Matthay KK, George RE, Yu AL. Promising therapeutic targets in neuroblastoma. Clinical Cancer Research 2012:18(10):2740-2753.

Dubois SG, Chesler L, Groshen S, Hawkins R, Goodarzian F, Shimada H, Tagan M, Stewart C, Mosse YP, Maris JM, Tsao-wei D, Marachelian A, Villablanca JG, Matthay KK. Phase I Study of Vincristine, Irinotecan, and ¹³¹I-Metaiodobenzylguanidine (¹³¹I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) Trial. Clin Cancer Res 2012; 18:2679-86. Epub 2012 Mar 15.

Seo Y, Gustafson WC, Dannoon SF, Nekritz EA, Lee CL, Murphy ST, VanBrocklin HF, Hernandez-Pampaloni M, Haas-Kogan DA, Weiss WA, Matthay KK. Tumor dosimetry using ¹²⁴I-mIBG microPET/CT for ¹³¹I-mIBG treatment of neuroblastoma in a murine xenograft model. Mol Imaging Biol 2012; Mar 2. [Epub ahead of print]

Update

Dr. Matthay received a 2010 Program Infrastructure renewal.