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Scintigraphic Imaging of Bacterial and Fungal Infection in Granulocytopenic Rats

Departments of Nuclear Medicine and Internal Medicine, University Hospital Nijmegen, Nijmegen
Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center Rotterdam, Rotterdam
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

Correspondence: For correspondence or reprints contact: Otto C. Boerman, PhD, Department of Nuclear Medicine, University Hospital Nijmegen, P.O. Box 9101, 6500HB Nijmegen, The Netherlands.

ABSTRACT

Scintigraphic imaging in granulocytopenic patient scan be very useful to detect and localize infections, which often do not show localizing signs and symptoms. We studied the potential of ^99mTc-labeled polyethylene glycol (PEG)-coated liposomes and ^99mTc-labeled lgG to image bacterial and fungal infection in a granulocy topenic rat model. ⁶⁷Ga-citrate was used as a reference agent. Methods: ^99mTc-PEG-liposomes, ^99mTc-hydrazinonicotinate (HYNIC)-lgG or ⁶⁷Ga-citrate was administered to granulocytopenic rats with a Staphylococcus aureus abscess or with unilateral invasive pulmonary aspergillosis. Imaging and biodistribution studies were performed. Results: All agents visualized the S. aureus infection from 1 h after injection onward. However, only with ^99mTc-PEG-liposomes and with ^99mTc-HYNIC-ldG did activity in the infectious foci increase with time up to 24 h. ^99mTc-PEG liposomes and ^99mTc-HYNIC-lgG showed significantly higher accumulation in the infectious focus compared with ⁶⁷Ga-citrate (1.33 ± 0.31 and 1.40 ± 0.16 percentage injected dose per gram [%ID/g], respectively, versus 0.31 ± 0.04 %ID/g 24 h after injection; P < 0.05). At 24 h after injection, abscess-to-muscle ratios were highest for ^99mTc-liposomes (72.1 ± 19.1), followed by ^99mTc-HYNIC-lgG (18.3 ± 3.3) and ⁶⁷Ga-citrate (4.4 ± 0.7). In pulmonary aspergillosis, both ^99mTc-PEG-liposomes and HYNIC-lgG showed significantly higher uptake in the infected lung than did ⁶⁷Ga-citrate (3.6 ± 0.4 and 8.3 ± 0.8 %ID/g, respectively, versus 1.3 %ID/g at 24 h after injection; P < 0.05). Conclusion: ^99mTc-PEG-liposomes ands ^99mTc-HYNIC-lgG performed better than did ⁶⁷Ga-citrate in the localization of peripheral bacterial infection and fungal infection in the lung in granulocytopenic rats. The high focal uptake and high target-to nontarget ratios of ^99mTc-PEG-liposomes and ^99mTc-HYNIC-lgG indicate that both radiopharmaceuticals may become valuable agents to image infection in granulocytopenic patients.

Key Words: granulocytopenia • infection • imaging • liposomes • immunoglobulin • abscess • aspergillosis

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