Overall objective: Develop and implement treatment planning approaches for optimizing radio-immunotherapy (RIT). The emphasis during the first period of funding was on developing analytical tools for achieving this objective. The emphasis in this application is on applying these tools in the analysis and optimization of novel and emerging RIT.
Specific Aims : 1. Calculate the expected therapeutic impact of prescribing, for each patient, the amount of unlabeled (cold) antibody (Ab) given in RIT of non-Hodgkin's Lymphoma; define a protocol for obtaining the optimum amount. 2. Using models of normal tissue histology for microdosimetry calculations, estimate expected normal tissue toxicity with alpha- emitter RIT; predict appropriate dose-escalation schedules for alpha- emitter RIT for minimal disease. 3. Continue support and development of techniques and software related to 3-D and patient-specific internal dosimetry. Background & Methods: 1. 131I-anti-Bl Ab has yielded durable complete responses in patients with otherwise untreatable non-Hodgkin's Lymphoma/ Currently, 131I-anti-Bl is preceded by a fixed amount of cold anti-Bl for all patients. This is thought to improve targeting by saturating rapidly accessible, non-tumor antigen sites. Total tumor burden will be estimated from CT and SPECT of 131I-anti-Bl patients. Absorbed dose and dose volume-histograms of several index tumors will be calculated to evaluate correspondence with response. Retrospective analyses will be conducted to see if """"""""underdosing"""""""" (too little Ab relative to tumor burden) led to reduced response and """"""""overdosing"""""""" to increased toxicity. 2. Alpha emitters are ideal for eradicating minimal or micrometastatic disease due to their short range and high energy. These properties also make it difficult to predict normal organ toxicity. Mathematical models of organ histology will be developed and used for microdosimetry calculations to evaluate toxicity in RIT trials directed against micrometastases. 3. The dosimetery methodologies developed under this grant have been implemented in a software package called 3D-ID (3d-Internal Dosimetry). This software has been provided to, and used by, several outside investigators in on-going collaborations.
Aim 3 will make it possible to continue upgrading and adding features to this software and also to continue investigating new, dosimetry-related, techniques for treatment planning. Summary: Completion of the aims will (1) markedly improve what is likely to become a prevalent therapy for Non-Hodgkin's Lymphoma and (2) will provide fundamental information for designing clinical trials of a novel and emerging approach for eradicating minimal disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA062444-07
Application #
6350149
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Stone, Helen B
Project Start
1995-04-01
Project End
2003-01-31
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
7
Fiscal Year
2001
Total Cost
$332,151
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Josefsson, Anders; Nedrow, Jessie R; Park, Sunju et al. (2016) Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer. Cancer Res 76:472-9
Song, Hong; Hedayati, Mohammad; Hobbs, Robert F et al. (2013) Targeting aberrant DNA double-strand break repair in triple-negative breast cancer with alpha-particle emitter radiolabeled anti-EGFR antibody. Mol Cancer Ther 12:2043-54
Sgouros, George; Frey, Eric; Wahl, Richard et al. (2008) Three-dimensional imaging-based radiobiological dosimetry. Semin Nucl Med 38:321-34
Sgouros, George (2005) Dosimetry of internal emitters. J Nucl Med 46 Suppl 1:18S-27S
Emfietzoglou, Dimitris; Kostarelos, Kostas; Papakostas, Alexandros et al. (2005) Liposome-mediated radiotherapeutics within avascular tumor spheroids: comparative dosimetry study for various radionuclides, liposome systems, and a targeting antibody. J Nucl Med 46:89-97
Kostarelos, Kostas; Emfietzoglou, Dimitris; Papakostas, Alexandros et al. (2004) Binding and interstitial penetration of liposomes within avascular tumor spheroids. Int J Cancer 112:713-21
Sgouros, George; Kolbert, Katherine S; Sheikh, Arif et al. (2004) Patient-specific dosimetry for 131I thyroid cancer therapy using 124I PET and 3-dimensional-internal dosimetry (3D-ID) software. J Nucl Med 45:1366-72
Ballangrud, Ase M; Yang, Wei-Hong; Palm, Stig et al. (2004) Alpha-particle emitting atomic generator (Actinium-225)-labeled trastuzumab (herceptin) targeting of breast cancer spheroids: efficacy versus HER2/neu expression. Clin Cancer Res 10:4489-97
Sgouros, George; Squeri, Shannon; Ballangrud, Ase M et al. (2003) Patient-specific, 3-dimensional dosimetry in non-Hodgkin's lymphoma patients treated with 131I-anti-B1 antibody: assessment of tumor dose-response. J Nucl Med 44:260-8
Palm, Stig; Enmon Jr, Richard M; Matei, Cornelia et al. (2003) Pharmacokinetics and Biodistribution of (86)Y-Trastuzumab for (90)Y dosimetry in an ovarian carcinoma model: correlative MicroPET and MRI. J Nucl Med 44:1148-55

Showing the most recent 10 out of 27 publications