Biodistribution and Clearance of 125I-labeled C-reactive Protein and 125I-labeled Modified C-reactive Protein in CD-1 Mice

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 approximately 50% of 125I-CRP was recoverable from plasma 5 min after injection, only approximately 5% of 125I-mCRP was similarly recoverable. The estimated volume of distribution at steady state calculated for either form of 125I-mCRP was approximately 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 approximately 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, approximately 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.