Page 146 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 7
The aim of this pilot study was to describe the performance of 89Zr-labeled- rituximab PET as an imaging biomarker to assess CD20 targeting in patients with relapsed/refractory diffuse large B cell lymphoma, by correlating tumor uptake of 89Zr-rituximab with CD20 expression in biopsied tumor lesions.
MATERIALS AND METHODS
Data used in this pilot study was obtained as part of an ongoing main trial (registered in the Dutch Trial Register http://www.trialregister.nl, NTR 3392) with formal ethical approval from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, The Netherlands (approval date July 2012, reference 2012/165). The study was performed in compliance with the principles of the Declaration of Helsinki. All patients signed an informed consent form.
Patients with a primary diagnosis of CD20-positive DLBCL, relapsed after or refractory to first line treatment with rituximab combined with anthracycline- based chemotherapy (R-CHOP), were eligible for inclusion. A 18F-FDG-PET scan was performed as routine clinical staging before start of second line treatment (7).
Patients were included before start of second line treatment with rituximab combined with cisplatin-based chemotherapy. Inclusion criteria consisted of age ≥18 years, WHO performance score 0-2 and eligibility for high dose chemotherapy and autologous stem cell transplant. Patients with known central nervous system (CNS) involvement were not eligible.
Tumor biopsies were obtained to confirm refractory/relapsed disease before start of second line treatment. IHC was performed, including at least staining for CD20, CD79a, CD3 and MIB1 to support the diagnosis. As part of the routine work-up CD20 expression was reported as either present (+) or absent (-). In addition, CD20 expression was assessed semi-quantitatively as:
A. Uniformly positive in all tumor cells.
B. Heterogeneously positive, ranging from positive in the majority
of cells to positivity limited to sparse groups of cells.
C. Absent, ranging from extremely sparse groups of CD20-positive cells to completely absent in all tumor cells, with a positive
internal control sample and CD79a-positive.
A qualitative assessment was made for membranous or granular staining patterns. Tumor biopsies were assessed by a pathologist blinded for immuno-PET results.
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