Research Papers:

Non-invasive visualization of tumor infiltrating lymphocytes in patients with metastatic melanoma undergoing immune checkpoint inhibitor therapy: a pilot study

Svetomir N. Markovic, Filippo Galli, Vera J. Suman, Wendy K. Nevala, Andrew M. Paulsen, Joseph C. Hung, Denise N. Gansen, Lori A. Erickson, Paolo Marchetti, Gregory A. Wiseman and Alberto Signore _

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Oncotarget. 2018; 9:30268-30278. https://doi.org/10.18632/oncotarget.25666

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Svetomir N. Markovic1,4, Filippo Galli2, Vera J. Suman3, Wendy K. Nevala4, Andrew M. Paulsen5, Joseph C. Hung5, Denise N. Gansen5, Lori A. Erickson6, Paolo Marchetti7, Gregory A. Wiseman5 and Alberto Signore2

1Department of Oncology, Mayo Clinic, Rochester, MN, USA

2Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, Rome, Italy

3Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

4Department of Immunology, Mayo Clinic, Rochester, MN, USA

5Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA

6Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

7Oncology Unit, Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, and IDI-IRCCS, Rome, Italy

Correspondence to:

Alberto Signore, email: [email protected]

Keywords: check point inhibitors; ipilimumab; pembrolizumab; melanoma; 99mTc-IL2

Received: December 28, 2017     Accepted: June 04, 2018     Published: July 13, 2018


Early in the course of immunotherapy there is frequently a transient enlargement of tumor masses (pseudo-progression) due to tumor infiltration by TILs. Current clinical imaging modalities are not able to distinguished pseudo-progression from true tumor progression. Thus, patients often remain on treatment 4-8 weeks longer to confirm disease progression. Nuclear medicine offers the possibility to image immune cells and potentially discriminate pseudo-progression and progression.

We conducted a pilot study in patients with metastatic melanoma receiving ipilimumab (IPI) or pembrolizumab (PEMBRO) to assess safety and feasibility of SPECT/CT imaging with 99mTc- interleukin-2 (99mTc-HYNIC-IL2) to detect TILs and distinguish between true progression from pseudo- progression. Scans were performed prior to and after 12w treatment. After labelling,99mTc-HYNIC-IL2 was purified and diluted in 10 mL of 5% glucose with 0.1% human serum albumin.

Of the 5 patients (2 treated with IPI and 3 with PEMBRO) enrolled, two failed to complete the second scan as they discontinued IPI due grade 3 colitis (1 patient) or patient refusal after developing multiple toxicities attributed to IPI (1 patient). Following the first scan, one patient reported to have a grade 1 pruritus with grade 1 pain. No other toxicities attributed to the radiopharmaceutical infusion were reported. Metastatic lesions could be visualized by 99mTc-IL2 imaging and there was positive correlation between size and 99mTc-HYNIC-IL2 uptake, both before and after 12 weeks of therapy.

The results of this pilot study demonstrate the safety and feasibility of 99mTc-IL2 imaging and has led to a number of hypotheses to be tested in future studies.

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