The effect of molecular weight on nonspecific accumulation of T-99m-labeled proteins in inflammatory foci

Although several proteins have been proposed and tested for scintigraphic d etection of infection, the most optimal characteristics of a protein for th is application have not yet been determined. Molecular weight (MW) of the p rotein, its charge, shape, carbohydrate content, characteristics of the rad ionuclide and receptor interactions are factors that could affect the in vi vo behavior of the infection imaging agent. The effect of molecular weight on nonspecific accumulation of Tc-99m-labeled proteins in inflammatory foci was studied in a rat model. Methods: Eleven proteins whose MWs ranged from 2.5 kDa up to 800 kDa were l abeled with Tc-99m using the hydrazinonicotinamide (HYNIC) chelator. Rats w ith S. aureus infection were injected i.v. with 15 MBq Tc-99m-labeled prote in. Gamma camera images were acquired and biodistribution of the radiolabel was determined ex vivo. Results: From biodistribution data no significant correlation was found bet ween abscess uptake and molecular size of the Tc-99m-labeled proteins that were studied. Fast blood clearance with predominant uptake in liver and spl een was found for the largest proteins (MW 669 kDa-800 kDA). For proteins o f intermediate size (MW 66 kDa -206 kDa) we found relatively slow blood cle arance with relatively moderate uptake in liver and spleen. For smaller pro teins (MW 2.5 kDa -29 kDa) rapid blood clearance with predominant kidney up take was observed. The abscess uptake of the Tc-99m-labeled proteins (%ID/g , 24 h p.i.) was highest for serum proteins IgG and BSA. Abscess uptake cor related well with blood levels: r = 0.95 and 0.84 at 4 and 24 h respectivel y (P < 0.005). The abscess-to-muscle ratios varied from 2.1 to 17.8 at 24 h p.i. with highest values for <alpha>-2 macroglobulin (MW 725 kDa) and the intermediate sized proteins (MW 66-206 kDa). Gamma camera imaging showed lo calization of all radiotracers at the site of infection with abscess-to-bac kground ratios (A/B) ranging from 1.4 to 7.0 (IgG) at 20 h p.i. The serum p roteins Ige and BSA showed highest blood levels and best infection imaging characteristics. Conclusion: Not molecular weight but blood residence time is the principal factor that determines localization of a nonspecific tracer protein in infe ctious foci. The ideal nonspecific infection imaging agent is a protein wit h a long circulatory half-life. From the proteins tested here Ige and album in showed the best characteristics for an infection imaging agent. (C) 2001 Elsevier Science Inc. All rights reserved.