{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:15:20Z","timestamp":1790972120005,"version":"4.1.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nucl. Med."],"abstract":"Introduction<\/jats:title>Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99m<\/jats:sup>Tc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89<\/jats:sup>Zr) is a positron emitter with a half-life of 78.4\u2005h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89<\/jats:sup>Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89<\/jats:sup>Zr-labelled leukocytes, using p<\/jats:italic>-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99m<\/jats:sup>Tc]Tc-HMPAO-labelled leukocytes.<\/jats:p><\/jats:sec>Methods<\/jats:title>Leukocytes were isolated from whole-blood samples of eight patients with clinically and\/or radiologically confirmed infection. Isolated leukocytes were labelled with [99m<\/jats:sup>Tc]Tc-HMPAO according to standardised methods, and [89<\/jats:sup>Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18\u2005h post injection of [99m<\/jats:sup>Tc]Tc-HMPAO-labelled leukocytes, and whole-body PET\/CT was performed 3 and 24\u2005h post injection of [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients.<\/jats:p><\/jats:sec>Results<\/jats:title>Successful [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7%\u2009\u00b1\u20093.6%; n<\/jats:italic>\u2009=\u20098). A mean high viability of [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98%\u2009\u00b1\u200912.51%). The [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99m<\/jats:sup>Tc]Tc-HMPAO- and [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99m<\/jats:sup>Tc]Tc-HMPAO-labelled leukocytes outperformed [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo<\/jats:italic> stability of the radiolabel.<\/jats:p><\/jats:sec>Discussion<\/jats:title>Although the [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89<\/jats:sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnume.2024.1426650","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T04:28:30Z","timestamp":1721622510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled 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