Biological disposition and imaging of a radioiodinated alkylphosphocholine in two rodent models of breast cancer.
Iodine-125-12-[m-iodophenyl]-dodecylphosphocholine (NM-324) has been shown to accumulate in a variety of animal tumor models. Moreover, preliminary pharmacokinetic studies with NM-324 are being conducted in cancer patients. The present study was undertaken to examine the potential application of NM-324 as a breast tumor-imaging agent.


METHODS
Two animal models of breast cancer were utilized: namely, syngenic inbred Lewis female rats bearing the rat mammary tumor (RMT) and athymic mice with HT-39 human tumor xenografts. After i.v. administration of NM-324, the tissue distribution of radioactivity was determined at various time points. Gamma camera scintigrams were also acquired to confirm the biodistribution results. Macro- and microautoradiography were used to analyze cellular distribution of radioactivity in tumors.


RESULTS
In the rat mammary tumor model, levels of radioactivity in the tumor reached a maximum at 24 hr after i.v. administration (1.65% ID/g, tumor-to-blood 6.4). These tumors could be visualized by gamma camera scintigraphy as early as 1 hour after administration. In the nude mouse model, levels of radioactivity in tumor reached a maximum at 48 hr after i.v. administration (4.96 %ID/g, tumor-to-blood 5.5). Tissues expected to interfere with the resolution of breast lesions such as fat, heart, lung and muscle displayed much lower concentrations of the radioactivity. Gamma camera scintigraphy confirmed the results observed from biodistribution experiments. Lipid extraction of the tumors and major organs in both animal models showed the sole presence of unchanged NM-324. Microautoradiographic analysis of slices of rat mammary and HT-39 tumors provided additional information regarding the intratumoral distribution of radioactivity.


CONCLUSIONS
The ability of radioiodinated phospholipid analogs to accumulate in breast tumors reinforces the need for further investigation of this type of radiopharmaceutical as tumor imaging agents.
Rampy
M A
MA
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Brown
R S
RS
Pinchuk
A N
AN
Weichert
J P
JP
Skinner
R W
RW
Fisher
S J
SJ
Wahl
R L
RL
Gross
M D
MD
Ethier
S P
SP
Counsell
R E
RE
D000818:Animals; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D010742:Phospholipid Ethers / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D007457:Iodine Radioisotopes; D010742:Phospholipid Ethers; C077315:NM 324