European Journal of Nuclear Medicine Vol. 29, No. 5, May 2002 Abstract. The aim of this study was to investigate wheth- er technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was la- belled with 99m Tc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections. For compari- son, we used two peptides for infection detection, i.e. UBI 29–41 and hLF 1–11, and human IgG, all labelled with 99m Tc. Mice were infected with Candida albicans or injected with heat-killed C. albicans or lipopolysaccha- rides to induce sterile inflammation. Also, mice were in- fected with Staphylococcus aureus or Klebsiella pneumo- niae. Next, accumulation of 99m Tc-fluconazole and 99m Tc- labelled peptides/IgG at affected sites was determined scintigraphically. 99m Tc-fluconazole detected C. albicans infections (T/NT ratio=3.6±0.47) without visualising bac- terial infections (T/NT ratio=1.3±0.04) or sterile inflam- matory processes (heat-killed C. albicans: T/NT ra- tio=1.3±0.2; lipopolysaccharide: T/NT ratio=1.4±0.1). C. albicans infections were already seen within the first hour after injection of 99m Tc-fluconazole (T/NT ratio= 3.1±0.2). A good correlation (R 2 =0.864; P<0.05) between T/NT ratios for this tracer and the number of viable C. al- bicans was found. Although 99m Tc-UBI 29–41 and 99m Tc- hLF 1–11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these 99m Tc- labelled peptides did not distinguish these fungal infec- tions from bacterial infections. It is concluded that 99m Tc- fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations. Keywords: Fluconazole – Antimicrobial peptides – Can- dida albicans – Aspergillus fumigatus – Technetium-99m labelling Eur J Nucl Med (2002) 29:674–679 DOI 10.1007/s00259-001-0760-7 Introduction Anticancer therapy, transplantation and AIDS give rise to infections with fungi, such as Candida albicans and Aspergillus fumigatus. The former is a major cause of mucosal and systemic infections [1, 2]. Aspergillus fu- migatus is a ubiquitous mold, which may cause invasive aspergillosis in transplant recipients. In this context it is clinically relevant to develop diagnostic tools that can discriminate fungal infections from bacterial infections and sterile inflammatory processes. A previous study re- ported on fungus imaging with fluorine-18 fluconazole and positron emission tomography (PET) [3]. Although Candida-infected tissues were rapidly visualised with this radiolabelled antifungal agent, this approach suf- fered from rather poor accumulation at sites of infection and high amounts of radioactivity were deposited in the liver. We hypothesised that technetium-99m-labelled flu- conazole might have different radiopharmacological characteristics. This article reports on our in vitro tests and animal experiments with 99m Tc-labelled fluconazole for improved detection of fungal infections. As compara- tive agents we included 99m Tc-labelled cationic peptides [4]. Ernest K.J. Pauwels ( ✉ ) Department of Radiology, Division of Nuclear Medicine, LUMC, Leiden, The Netherlands e-mail: E.K.J.Pauwels@LUMC.nl Tel.: +31-71-5263475, Fax: +31-71-5266751 Short communication Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of Candida albicans and Aspergillus fumigatus infections Antonella Lupetti 1, 2 , Mick M. Welling 3 , Ulderico Mazzi 4 , Peter H. Nibbering 1 , Ernest K. J. Pauwels 3, 5 1 Department of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands 2 Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università degli Studi di Pisa, Pisa, Italy 3 Department of Radiology, Division of Nuclear Medicine, LUMC, Leiden, The Netherlands 4 Dipartimento di Scienze Farmaceutiche, Università degli Studi di Padova, Padova, Italy 5 Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center (LUMC), C4-Q, P. O. Box 9600, 2300 RC Leiden, The Netherlands Accepted 20 December 2001 / Published online: 6 March 2002 © Springer-Verlag 2002