Evaluation of 99mTc(CO)5I as a potential lung perfusion agent.
BACKGROUND
The use of (99m)Tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)(5)I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m)Tc(CO)(5)I and its potential as a lung perfusion agent.


METHODS
(99m)Tc(CO)(5)I was synthesized by carbonylation of (99m)TcO(4-) at 160 atm of CO at 170 degrees C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using (99)Tc(CO)(5)I as a reference. (99m)Tc(CO)(5)I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) and (99m)TcO(4-) for comparison. (99m)Tc(CO)(5)I was administered intravenously to Sprague-Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using (99m)Tc-MAA.


RESULTS
Radiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of (99)Tc(CO)(5)I. The dynamic images showed that 70% of (99m)Tc(CO)(5)I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, (99m)TcO(4-) rapidly washed out of the lungs after administration. As expected (99m)Tc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ +/-S.D. at 1 h for (99m)Tc(CO)(5)I was as follows: blood, 0.22+/-0.02; lung, 12.8+/-2.87; liver, 0.8+/-0.15; heart, 0.15+/-0.01; kidney, 0.47+/-0.08. The percentage of injected dose per organ +/-S.D. at 1 h was as follows: lung, 22.47+/-2.31; liver, 10.53+/-1.8; heart, 0.18+/-0.01; kidney, 1.2+/-0.17. Tissue distribution studies with (99m)Tc-MAA showed 100% lung uptake.


CONCLUSIONS
(99m)Tc(CO)(5)I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of (99m)Tc-pentacarbonyl complexes is warranted.
Miroslavov
Alexander E
AE
Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia.
Gorshkov
Nikolay I
NI
Lumpov
Alexander L
AL
Yalfimov
Anatoly N
AN
Suglobov
Dmitrii N
DN
Ellis
Beverley L
BL
Braddock
Rattana
R
Smith
Anne-Marie
AM
Prescott
Mary C
MC
Lawson
Richard S
RS
Sharma
Harbans L
HL
D000818:Animals; D006639:Histidine / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging*; D055420:Perfusion Imaging / Q000379:methods*; D011817:Rabbits; D011854:Radiochemistry; D051381:Rats; D017556:Technetium Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D051598:Whole Body Imaging
D017556:Technetium Compounds; C539759:iodopentacarbonyltechnetium(I); D006639:Histidine