Metal ion speciation in blood plasma: gallium-67-citrate and MRI contrast agents.

plex biological fluids. In this article, we describe the chemical speciation of Ga(III) and Gd(III), two metal ions commonly used to prepare imaging agents and MRI contrast agents respectively. We hope to show how a knowledge of chemical speciation can help to explain existing clinical data and how it can be used in the design of new and more effective agents. X@((t.J), Metal chelate ions are commonly used in medical diagnostic imag ing as MRIcontrastor imagingagents.Theefficacyof thesemetals depends on their in vivo behavior, which in turn depends on their in vivo speciation. Methods: A computer model has been used to simulate the speciation of Ga3@and Gd3@in blood plasma. The model has been tested against known clinicaldata and then used to investigate Ga3@ uptake by tumor cells. The iatrogenic effect of a gadopentetic acid enhanced MRIscan upon the biodistilbution of 67Gacitratehasalsobeencalculated. Results:Thespeciation of @3± calculated using the computer model is concordant with clinical data. The results support transfernn mediated uptake of Ga3@by tumor cells but also account for GaQII)biodistribution observed inhypotransfemnemic Ina studyof the effectof gadopentetic acidupon67Ga galliumcitrate,neitherresidual DTPA nor (Gd(DTPA)J2 cause signfficant changes in the speciation of Ga(III).The calculations show that dissociation of 4% of the admin istered gadopentetic acid results in the formation of a mixed, Gd(III) and Ga(III),metal transfernn complex and a 100-fold increase in the concentration of (Ga(OH)@J. Conclusion: Computer simulation is a valuable tool which can be used to explain/understand in vivo behavior of radioactive metal ions.