Abstract

Introduction
Tumor Associated Macrophages (TAM) play a role in shaping the tumor micro-environment (TME). An imbalance between pro-inflammatory and immunosuppressive, protumorigenic TAMs can support tumor growth and induce resistance to therapy. The presence of protumorigenic TAMs can be assessed by immunohistochemistry (IHC), but due to tumor heterogeneity and locations unable to take biopsies, the use of whole-body PET/CT is wanted. That is why a new PET-tracer is developed, a 68Ga labeled nanobody (Nb) targeting macrophage mannose receptor (MMR), expressed by the protumorigenic TAMs.

Methods
Patients (pts) with a solid tumor of at least 10 mm, ECOG score of 2 or lower and a good renal and hepatic function are eligible for inclusion in this phase I study. Safety is assessed using clinical examination and blood sampling before and 3h post injection (p.i.). Biodistribution and dosimetry is assessed using multiple blood samples for blood activity assessment and using PET/CT scans at 10, 90 and 150 min p.i. Blood and urine is assessed for metabolites. Cytokines are measured before and up to 24h p.i. to exclude macrophage activation.

Results/Discussion
Up to today, two pts were injected with 174MBq and 132MBq of Nb. Both were lung cancer patients treated with immunotherapy without complete radiological response. No adverse events (AE) were recorded, confirming safety in the first two subjects. Biodistribution analysis showed rapid blood clearance with <10% in total blood volume at 3h p.i. (fig. 1). PET/CT showed high tracer uptake in liver, spleen, adrenals and kidneys, as was expected from preclinical data. Other organs showed a very low background activity, with good potential to assess tumor lesions in such parts of the body. No uptake in tumor lesions was seen, but correlation to IHC was not available for these patients. Full biodistribution and dosimetry analysis is ongoing and will be presented at the meeting. Four additional patients will be recruited in the coming weeks.

Conclusions
68Ga-MMR-Nb PET/CT was well tolerated, without AE reported in the first two patients. The biodistribution is favorable, with the highest uptake in the kidneys, liver, spleen and adrenals. Further assessment in 4 pts is needed to complete the phase I study. A phase II study to compare with IHC is subsequently planned in a seamless phase I/II design.

Acknowledgment
We would like to thank Yasmine De Maeyer, Sonja Van den Block and Gratienne Van Holsbeeck for their contribution to the study. Also Kom op tegen Kanker and FWO to make our project possible.
Original languageEnglish
Publication statusPublished - 25 Aug 2020
Event15th European Molecular Imaging Meeting - Thessaloniki, Greece
Duration: 25 Aug 202028 Aug 2020

Conference

Conference15th European Molecular Imaging Meeting
CountryGreece
CityThessaloniki
Period25/08/2028/08/20

Keywords

  • Cancer
  • Macrophage

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