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

Introduction: Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]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 (89Zr) 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 [89Zr]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 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes. Methods: Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients. Results: Successful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel. Discussion: Although the [89Zr]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 [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.

One-day protocol versus two-day protocol in acquisition of scintigraphy with "in vitro" labelled white blood cells for diagnosis of osteoarticular infection. / Protocolo de un día vs protocolo de dos días de adquisición mediante gammagrafía con leucocitos marcados in vitro para el diagnóstico de infección osteoarticular.

INTRODUCTION: It is difficult to determine osteoarticular infection and differentiate inflammation from infection with laboratory and imaging procedures (CT, MRI, US). Labelled white-blood-cell scintigraphy (WBCS) is the nuclear medicine test of choice but it takes two days, sometimes finds it difficult to differentiate soft tissue from bone infection and therefore causes interobserver variability, which decreases its specificity. OBJECTIVE: To demonstrate the usefulness of the one-day protocol with time decay-corrected acquisition in WBCS to diagnose osteoarticular infection and to reduce interobserver variability. The role of SPECT/CT in WBCS in locating the infected focus was also evaluated. METHODS: 110 patients with suspected osteoarticular infection were studied prospectively. Planar images were obtained with time decay-corrected acquisition at 30min, 4h, 8h and 24h. WBCS planar images were grouped in two protocols: One-day protocol: experts evaluated 30min, 4h and 8h images. Two-day protocol: experts evaluated 30min, 4h and 24h images. Both protocols were classified as: SPECT/CT was performed in 72 patients. Kappa index was calculated to evaluate interobserver variability. RESULTS: Infection was confirmed in 34 cases. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 97.1%, 97.4%, 94.3%, 98.7%, and 97.3% for the one-day protocol and 94.1%, 97.4%, 94.1%, 97.4%, and 96.4% for two-days-protocol. SPECT/CT contributed to diagnosis in 45/50 patients with planar WBCS positive. Kappa index: 0.8 for one-day protocol and 0.79 for two-day protocol, respectively. CONCLUSION: One-day protocol with time decay-corrected acquisition WBCS and SPECT/CT enables early and accurate diagnosis of osteoarticular infection.

Utility of 11C-methionine and 11C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model: comparison to autologous 111In-labelled leukocytes, 99m Tc-DPD, and 18F-FDG.

The aim of this study was to compare 11C-methionine and 11C-donepezil positron emission tomography (PET) with 111In-labeled leukocyte and 99m Tc-DPD (Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid) single-photon emission computed tomography (SPECT), and 18F-fluorodeoxyglucose (18F-FDG) PET to improve detection of osteomyelitis. The tracers' diagnostic utility where tested in a juvenile porcine hematogenously induced osteomyelitis model comparable to osteomyelitis in children. Five 8-9 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, 11C-methionine and 11C-donepezil PET, 99m Tc-DPD and 111In-labelled leukocytes scintigraphy, and 18F-FDG PET. This was followed by necropsy of the pigs and gross pathology, histopathology, and microbial examination. The pigs developed a total of 24 osteomyelitic lesions, 4 lesions characterized as contiguous abscesses and pulmonary abscesses (in two pigs). By comparing the 24 osteomyelitic lesions, 18F-FDG accumulated in 100%, 111In-leukocytes in 79%, 11C-methionine in 79%, 11C-donepezil in 58%, and 99m Tc-DPD in none. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT and 11C-methionine in marking infectious lesions.