Biodistribution, metabolism, and excretion of radioiodinated phospholipid ether analogs in tumor-bearing rats.
The phospholipid ether analog, [125I]-1-O-[12-(m-iodophenyl)dodecyl]propanediol-3-phosphocholine (NM-295) was synthesized and evaluated for its ability to visualize tumors. Preliminary studies were performed in rats bearing the Walker 256 carcinosarcoma. Most of the radioactivity was cleared from the animals during the first 24 hours. However, the tumor showed a decreased rate of clearance of radioactivity when compared with non-target tissue. This difference in the clearance rate allowed for excellent images of the tumor at 24 hours. Scintigraphic images compared favorably with other radioiodinated phospholipid ether analogs such as [125I-rac-1-O-[12-(m-iodophenyl)dodecyl]-2-O-methylglycero-3- phosphocholine (NM-294) and [125I]-12-(m-iodophenyl)dodecyl phosphocholine (NM-324). In contrast with the latter two compounds, however, tissue distribution studies revealed that NM-295 cleared at a much faster rate from all tissues, including tumor. In addition, within 24 hours following administration of NM-295, over 70% of the radioactivity was excreted as compared to 50% and 20% for NM-294 and NM-324, respectively. The majority of excreted radioactivity appeared in the urine for all three compounds. Thin-layer chromatography of urine and fecal extracts showed the presence of metabolites only. In contrast, lipid extracts of either liver or tumor demonstrated only the presence of the parent compound. Therefore, these data suggest that in each case it was the parent phospholipid analog that was taken up and retained by the tissues, while the metabolic product(s) was cleared and excreted from the animal.
Plotzke
K P
KP
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Rampy
M A
MA
Meyer
K
K
Ruyan
M
M
Fisher
S J
SJ
Wahl
R L
RL
Skinner
R W
RW
Gross
M D
MD
Counsell
R E
RE
D000818:Animals; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D010742:Phospholipid Ethers / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; C087112:NM 295; D010742:Phospholipid Ethers; C063292:NM 294; C077315:NM 324