The Open Nuclear Medicine Journal

2012, 4 : 14-20
Published online 2012 June 1. DOI: 10.2174/1876388X01204010014
Publisher ID: TONMEDJ-4-14

Eleven-Year Experience with the Avidin-Biotin Pretargeting System in Glioblastoma: Toxicity, Efficacy and Survival

Chiara M. Grana , Marco Chinol , Concetta De Cicco , Mirco Bartolomei , Marta Cremonesi , Lisa Bodei , Paola A. Rocca , Monica Pacifici , Simone Tiberini , Silvia M. Baio , Giovanni Broggi , Stefano Severi and Giovanni Paganelli
Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy.

ABSTRACT

Background:

The 3-step avidin-biotin pretargeting approach is applied in patients with recurrent glioblastoma (GBM), using biotinylated anti-tenascin monoclonal antibody as the first step of pretargeting followed by avidin and 90Ybiotin.

Methods:

The present study reviews objective response and overall survival rates in 502 glioblastoma patients treated with 3-step radioimmunotherapy in our institute from December 1994 to December 2005. Patients underwent standard treatment before receiving Pretargeted Antibody-Guided Radionuclide Therapy with 90Y-biotin (PAGRIT®).

Results:

Of the 502 patients, 272 (54%) were evaluable for response and 375 (75%) for overall survival. 174 patients (64%) continued to progress after PAGRIT®, 77 (28%) obtained disease stabilization, and 21 (8%) showed objective tumor regression. Survival of the 375 evaluable patients was 98.4% at 6 months, 79.2% at 12 months, 51.7% at 18 months, and 30.7% at 24 months after the first cycle of PAGRIT®. All 375 received 3-step PAGRIT® at recurrence of GBM. The median survival time from diagnosis was 19 months.

Conclusion:

The results from this retrospective analysis suggest that 90Y-biotin PAGRIT® interferes with the progression of glioblastoma, prolonging survival in a larger number of patients. Our analysis forms the basis for further prospective trials, where radioimmunotherapy, which is known to be more effective in minimal residual disease, could be offered immediately after surgery.

Keywords:

Avidin-biotin, brain tumor, glioblastoma, monoclonal antibodies, pretargeting, radioimmunotherapy, tenascin.