Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in micevan der Veen, E. L., Suurs, F. V., Cleeren, F., Bormans, G., Elsinga, P. H., Hospers, G. A. P., Lub-de Hooge, M. N., de Vries, E. G. E., de Vries, E. F. J. & F Antunes, I., 28-Feb-2020, In : Journal of Nuclear Medicine. 36 p.
Research output: Contribution to journal › Article › Academic › peer-review
Recently, N-(4-18F-fluorobenzoyl)-interleukin-2 (18F-FB-IL2) was introduced as PET tracer for T-cell imaging. However, production is complex and time-consuming. Therefore, we developed two radiolabeled interleukin-2 (IL-2) variants, namely aluminum 18F-fluoride-(restrained complexing agent)-IL-2 (18F-AlF-RESCA-IL2) and 68Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL-2 (68Ga-Ga-NODAGA-IL2) and compared their in-vitro and in-vivo characteristics with 18F-FB-IL2. Methods: Radiolabeling of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 was optimized and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex-vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60 and 90 min after tracer injection. In-vivo binding characteristics were studied in severe combined immune-deficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMCs inoculation and a 60-min dynamic PET scan was acquired, followed by ex-vivo biodistribution studies. Specific uptake was determined by co-injection of tracer with unlabeled IL2 and by evaluating uptake in a control group inoculated with Matrigel only. Results:68Ga-Ga-NODAGA-IL2 and 18F-AlF-RESCA-IL2 were produced with radiochemical purity >95% and radiochemical yield of 13.1±4.7% and 2.4±1.6% within 60 and 90 min, respectively. Both tracers were stable in serum, with >90% being intact tracer after 1h. In-vitro, both tracers displayed preferential binding to activated hPBMCs. Ex-vivo biodistribution studies in BALB/c mice showed higher uptake of 18F-AlF-RESCA-IL2 than 18F-FB-IL2 in liver, kidney, spleen, bone and bone marrow. 68Ga-Ga-NODAGA-IL2 uptake in liver and kidney was higher than 18F-FB-IL2 uptake. In-vivo, all tracers revealed uptake in activated hPBMCs in SCID mice. Low uptake was seen after a blocking dose of IL2 or in the Matrigel control group. In addition, 18F-AlF-RESCA-IL2 yielded highest contrast PET images of target lymph nodes. Conclusion: Production of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 is simpler and faster than 18F-FB-IL2. Both tracers showed good in-vitro and in-vivo characteristics with high uptake in lymphoid tissue and hPBMC xenografts.
|Number of pages||36|
|Journal||Journal of Nuclear Medicine|
|Publication status||E-pub ahead of print - 28-Feb-2020|