Synthesis, biodistribution and imaging properties of indium-111-DTPA-paclitaxel in mice bearing mammary tumors.
Paclitaxel, an antineoplastic agent that stabilizes microtubules and arrests cells in the G2/M cell cycle phase, has shown activity against many common cancers, including ovarian and breast tumors. In order to evaluate the potential value of radiolabeled paclitaxel as an imaging tool in tumors, we synthesized 111In-DEPA-paclitaxel and investigated its biodistribution and gamma scintigraphic imaging properties.


METHODS
Mice bearing a paclitaxel-responsive mammary tumor (MCA-4) were used. DTPA-paclitaxel was labeled with 111In with a radiochemical yield of 84% and radiochemical purity of 90%. Each mouse received 5 microCi of radiotracers intravenously for biodistribution studies and 100 microCi for gamma scintigraphic studies. Indium-111-DTPA was used as a control.


RESULTS
In tumor-bearing mice, 111In-DTPA was characterized by rapid clearance from the plasma with negligible retention in the tumor, the liver and other body parts. In contrast, 111In-DTPA-paclitaxel exhibited a pharmacological profile resembling that of paclitaxel. Furthermore, a significant uptake of 111In-DTPA-paclitaxel was observed in the tumor. The tumor-to-muscle ratios were 2.64, 3.16 and 6.94 at 30 min, 2 hr and 24 hr, respectively, although absolute uptake in the tumor decreased from 1.95% (injected dose/g) at 30 min to 0.21% at 24 hr after injection. The tumor-to-blood ratio reached 50 at 24 hr after injection. Gamma scintigraphy and autoradiographic studies clearly showed the retention of radiolabeled paclitaxel in the tumor 24 hr after injection.


CONCLUSIONS
These studies suggest that 111In-DTPA-paclitaxel may be clinically useful in studying the uptake of paclitaxel in solid tumors.
Li
C
C
Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Yu
D F
DF
Inoue
T
T
Yang
D J
DJ
Tansey
W
W
Liu
C W
CW
Milas
L
L
Hunter
N R
NR
Kim
E E
EE
Wallace
S
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D001345:Autoradiography; D002614:Chelating Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D017239:Paclitaxel / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D002614:Chelating Agents; D007205:Indium Radioisotopes; D004369:Pentetic Acid; D017239:Paclitaxel