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. 2008 Jan;49(1):30-8.
doi: 10.2967/jnumed.107.046938. Epub 2007 Dec 12.

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6

Michael R Zalutsky  1 , David A Reardon, Gamal Akabani, R Edward Coleman, Allan H Friedman, Henry S Friedman, Roger E McLendon, Terence Z Wong, Darell D Bigner
Affiliations

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6

Michael R Zalutsky et al. J Nucl Med. 2008 Jan.

Abstract

alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors.

Methods: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed.

Results: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was < or = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively.

Conclusion: This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.

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Figures

FIGURE 1
FIGURE 1
Serial whole-body anterior γ-camera images obtained after injection of 73 MBq of 211At-ch81C6 into SCRC of patient 1. (A) 100% window. (B) 1% window set to enhance areas with low activity concentrations. Focal activity seen in lower part of image is imaging standard.
FIGURE 2
FIGURE 2
Clearance of 211At activity from SCRC, determined by setting region of interest around cavity on serial γ-camera images obtained after administration of 211At-ch81C6 into SCRC. Data are for patients 1 (○), 2 (▽), 3 (▼), 4 (⬢), 7 (△), 8 (●), 12 (□), 13 (◆), 14 (◇), 15 (▲), and 17 (■).
FIGURE 3
FIGURE 3
%ID of 211At-ch81C6 in blood pool as function of time, determined from serial blood sample counts. Data are for patients 1 (○), 2 (▽), 3 (▼), 7 (△), 8 (●), 12 (□),13 (◆), 14 (◇), 15 (▲), and 17 (■).
FIGURE 4
FIGURE 4
Serial MRI images (gadolinium-enhanced T1-weighted images, axial plane) of representative patient after 211At-ch81C6 therapy. After gross total resection, SCRC rim was minimally enhanced. After 211At-ch81C6 administration, rim enhancement gradually became more prominent as SCRC retracted. Focal nodular enhancement noted 57 wk after 211At-ch81C6 administration was subsequently confirmed to be recurrent anaplastic oligodendroglioma.
FIGURE 5
FIGURE 5
Kaplan–Meier overall survival estimates for patients receiving 211At-ch81C6, stratified by histologic findings. GBM = glioblastoma multiforme.
See this image and copyright information in PMC

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