TECHNETIUM-99M-WHITE BLOOD CELL-SPECIFIC IMAGING AGENT DEVELOPED FROMPLATELET FACTOR-4 TO DETECT INFECTION

We have developed a leukocyte-avid, Tc-99m-labeled peptide (P483H) as a potential imaging agent for infection. P483H contains the heparin-bi nding region of platelet factor-4 (PF-4) and a lysine-rich sequence fo r rapid renal clearance. Technetium-99m-P483H was evaluated for its ab ility to selectively label white blood cells (WBCs) in vitro and to de tect focal E. coli infections in rabbits. Methods: Technetium-99m-P483 H was incubated with citrated whole human blood, layered onto WBC isol ation media and subjected to density gradient centrifugation to measur e WBC-associated radioactivity. Indium-111-WBCs and Tc-99m-gluceptate were used as controls. In the in vivo model, E. coli infected rabbits were imaged and necropsied 4 hr after administration of Tc-99m-P483H. Infected and contralateral control muscles were evaluated for %ID, %ID /g, I-max (muscle sample showing the highest uptake, i.e., %ID/g) and I-max-to-blood and I-max-to-control muscle ratios. Indium-111-WBCs, In -111-DTPA, I-131-albumin (HSA), Tc-99m-nanocolloid, Ga-67 and Tc-99m-g luceptate were evaluated as in vivo controls. Results: Technetium-99m- P483H associated predominantly with WBCs in vitro, and Tc-99m-p483H pr ovided high contrast images of infection in vivo. In vitro, 73% of Tc- 99m-P483H radioactivity was associated with WBCs. Technetium-99m-P483H outperformed In-111-WBCs, In-111-DTPA, 311-albumin, Tc-99m-nanocolloi d, Ga-67-citrate and Tc-99m-gluceptate with an infection I-max average of 0.062 %ID/g (+/-0.029; n = 48). Technetium-99m-P483H also outperfo rmed all controls, including In-111-WBCs, In-111-DTPA, I-131-albumin, Tc-99m-nanocolloid, Ga-67-citrate and Tc-99m-gluceptate. The I-max-to- blood and I-max-to-control muscle ratios for Tc-99m-P483H averaged 3.1 (+/-2.4) and 26.8 (+-16.8), respectively, and again outperformed all controls. Conclusion: Technetium-99m-P483H associates predominantly wi th WBCs in vitro and identified focal infections in vivo within 4 hr v ersus conventional imaging agents. Additionally, the agent showed rapi d blood clearance and exclusive renal excretion, which provides a clea r abdominal field for imaging abdominal infections.