Vol. 26, Issue 10, 977-981, October 1998

Biodistribution and Clearance of ¹²⁵I-Labeled C-Reactive Protein and ¹²⁵I-Labeled Modified C-Reactive Protein in CD-1 Mice

Marjan Motie, Katie W. Schaul, and Lawrence A. Potempa

Immtech International Inc.

Iodinated forms of C-reactive protein (CRP), soluble modified CRP (mCRP-sol), and suspended mCRP (mCRP-susp) were injected iv into CD-1 mice, for analysis of their pharmacokinetics (PK) and biodistribution (BD). The plasma half-life of ¹²⁵I-CRP, measured as 4.7 hr, agrees closely with previous reports. The PK and BD characteristics for ¹²⁵I-mCRP-sol and ¹²⁵I-mCRP-susp were comparable to each other and were distinctly different from those measured for CRP. Whereas ~50% of ¹²⁵I-CRP was recoverable from plasma 5 min after injection, only ~5% of ¹²⁵I-mCRP was similarly recoverable. The estimated volume of distribution at steady state calculated for either form of ¹²⁵I-mCRP was ~10-fold greater than that calculated for ¹²⁵I-CRP (23.4-27.6 and 2.4 ml, respectively). The estimated mean residence times for ¹²⁵I-mCRP were ~2 times longer than that measured for ¹²⁵I-CRP (9.5-11.5 hr, compared with 4.9 hr). At both 4- and 24-hr time points, substantial amounts of ¹²⁵I-mCRP were selectively distributed in the bone marrow. At 24 hr, ~25% of the injected ¹²⁵I-mCRP-sol and ¹²⁵I-mCRP-susp was localized to the bone marrow (corresponding to 92% of injected dose/g of tissue). At this time point, only 8% (or 27%/g) of ¹²⁵I-CRP was localized to the bone marrow. Overall, the data presented indicate that 1) mCRP has PK and BD characteristics distinct from those of CRP; 2) injected mCRP, although it is rapidly cleared from the general circulation, accesses large body areas and is selectively localized to the bone marrow; and 3) all forms of CRP appear to be excreted in the urine.