AUTHOR=Kahts Maryke , Summers Beverley , Ndlela Akhona Nkokheli , Gutta Aadil , Nemutaduni Phumudzo , More Andrew , Parsoo Aman , Ebenhan Thomas , Zeevaart Jan Rijn , Aras Omer , Sathekge Mike Machaba 

TITLE=First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes

JOURNAL=Frontiers in Nuclear Medicine

VOLUME=4

YEAR=2024

URL=https://www.frontiersin.org/journals/nuclear-medicine/articles/10.3389/fnume.2024.1426650

DOI=10.3389/fnume.2024.1426650

ISSN=2673-8880

ABSTRACT=<sec><title>Introduction</title><p>Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([<sup>99m</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 (<sup>89</sup>Zr) is a positron emitter with a half-life of 78.4 h, 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 [<sup>89</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 <sup>89</sup>Zr-labelled leukocytes, using <italic>p</italic>-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [<sup>99m</sup>Tc]Tc-HMPAO-labelled leukocytes.</p></sec><sec><title>Methods</title><p>Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [<sup>99m</sup>Tc]Tc-HMPAO according to standardised methods, and [<sup>89</sup>Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [<sup>99m</sup>Tc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients.</p></sec><sec><title>Results</title><p>Successful [<sup>89</sup>Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; <italic>n</italic> = 8). A mean high viability of [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [<sup>89</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 [<sup>99m</sup>Tc]Tc-HMPAO- and [<sup>89</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 [<sup>99m</sup>Tc]Tc-HMPAO-labelled leukocytes outperformed [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the <italic>in vivo</italic> stability of the radiolabel.</p></sec><sec><title>Discussion</title><p>Although the [<sup>89</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 [<sup>89</sup>Zr]Zr-Df-Bz-NCS-labelled leukocytes.</p></sec>