Alteration of the organ uptake of the (99m)Tc-radiopharmaceuticals, (99m)Tc-DPD, (99m)Tc-DMSA, (99m)Tc-tin colloid and (99m)Tc-MAA, induced by the applied cytotoxic drugs methotrexate sodium and cyclophosphamide.
OBJECTIVE
To investigate the influence of certain cytotoxic drugs on the organ uptake of the following (99m)Tc-radiopharmaceuticals: (99m)Tc-2,3-dicarboxypropane-1,1-diphosphonic acid ((99m)Tc-DPD), (99m)Tc-meso-2,3-dimercaptosuccinic acid ((99m)Tc-DMSA), (99m)Tc-tin colloid and (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). Methotrexate sodium and cyclophosphamide were used as models to evaluate these effects.


METHODS
Two groups of healthy male Wistar rats were treated separately by oral application of the drugs for 7 days. On the eighth day, each of the (99m)Tc-radiopharmaceuticals was applied in a separate group of treated animals. They were sacrificed at different time intervals and the radioactivity in the organs of interest was measured. The organ uptake of the (99m)Tc-radiopharmaceuticals in an additional control group of animals was also studied.


RESULTS
The results obtained showed an alteration in the organ uptake of (99m)Tc-radiopharmaceuticals in animals treated with cytotoxic drugs. In rats treated with methotrexate sodium, there was a higher uptake of (99m)Tc-DMSA in the bones, stomach and intestine, a higher uptake of (99m)Tc-DPD in the bones, intestine, blood and muscle, a lower uptake of (99m)Tc-tin colloid in the liver and a lower accumulation of (99m)Tc-MAA in the lungs. Cyclophosphamide-treated animals showed enhanced uptake of (99m)Tc-DMSA in the kidneys, a twofold enhanced uptake of (99m)Tc-DPD in all organs except the stomach, a decreased uptake of (99m)Tc-tin colloid in the lungs, spleen and kidneys and a significantly decreased uptake of (99m)Tc-MAA in the lungs.


CONCLUSIONS
These results confirm that both methotrexate sodium and cyclophosphamide may alter the organ uptake of (99m)Tc-radiopharmaceuticals in experimental animals.
Janković
Drina Lj
DLj
Vinca Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade, Serbia and Montenegro. drinaj@vin.bg.ac.yu
Djokić
Divna Dj
DDj
D000818:Animals; D003520:Cyclophosphamide / Q000493:pharmacokinetics*; D004164:Diphosphonates / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D017556:Technetium Compounds / Q000493:pharmacokinetics*; D013668:Technetium Tc 99m Aggregated Albumin / Q000494:pharmacology*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics*; D017971:Tin Compounds / Q000493:pharmacokinetics*
D004164:Diphosphonates; D007166:Immunosuppressive Agents; D015609:Organotechnetium Compounds; D017556:Technetium Compounds; D013668:Technetium Tc 99m Aggregated Albumin; D017971:Tin Compounds; C033905:technetium Tc 99m 1,1-diphosphonopropane-2,3-dicarboxylic acid; C033493:technetium Tc 99m tin colloid; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D003520:Cyclophosphamide; D008727:Methotrexate