1. Non-invasive clinical visualization of tumor infiltrating lymphocytes in patients with metastatic melanoma undergoing immune checkpoint inhibitor therapy: A pilot study
- Author
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Paolo Marchetti, Gregory A. Wiseman, Lori A. Erickson, Alberto Signore, Vera J. Suman, Svetomir N. Markovic, Denise N. Gansen, Joseph C. Hung, Andrew Paulsen, Filippo Galli, and Wendy K. Nevala
- Subjects
Cancer Research ,Metastatic melanoma ,Tumor-infiltrating lymphocytes ,business.industry ,Immune checkpoint inhibitors ,Non invasive ,Cancer ,medicine.disease ,Immune therapy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,In patient ,business ,030215 immunology - Abstract
3034 Background: Unique to modern immune therapy for cancer is that early in the course of treatment, patients frequently exhibit transient tumor enlargement (pseudo-progression, pPROG) due to tumor infiltration by lymphocytes (TIL). Currently, pPROG cannot be reliably distinguished from true tumor progression (PROG). There is a need for biomarker techniques to discriminate pPROG (effect of therapy) and PROG (therapy failure). Nuclear medicine offers radiopharmaceuticals capable of imaging immune cells; images can be fused to evaluate functional and anatomic characteristics of tumors, and potentially discriminate pPROG from PROG. Methods: In our study of metastatic melanoma patients, SPECT/CT imaging with 99mTc-interleukin-2 (99mTc-IL2) was performed to visualize TIL. Images were collected before/after 12 weeks of ipilimumab (IPI) or pembrolizomab (PEMBRO) therapy. The 99mTc-IL2 tracer was synthesized by conjugating succinimidyl-6-hydrazinopyridine-3-carboxylate (HYNIC-NHS) with commercial interleukin-2 (Aldesleukin). HYNIC-IL2 was incubated with tricine, 99mTcO4- (370-740 MBq) and SnCl2. After labelling 99mTc-IL2 was purified by reverse-phase chromatography and diluted in 5% glucose with 0.1% human albumin before injection. Five patients were enrolled in this study. Two patients failed to complete the 12 week 99mTc-IL2 scan due to discontinuation of IPI after: 1) grade 3 colitis and 2) patient refusal for adverse events attributed to IPI. No adverse events attributable to the tracer infusion were reported. Results: Metastatic lesions could be visualized by the tracer. Some lesions decreased in size, while others increased. A positive correlation was found between size and 99mTc-IL2 uptake, before and after therapy, suggesting the potential discrimination of tumor PROG (no 99mTc-IL2 uptake) from pPROG (high 99mTc-IL2 uptake). Immunohistochemical staining for TIL of 99mTc-IL2 positive and negative lesions are illustrated. Conclusions: The results demonstrate feasibility of 99mTc-IL2 imaging as a clinically useful tool capable of discriminating tumor PROG from pPROG. A clinical validation study is in progress. Clinical trial information: NCT01789827.
- Published
- 2017
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