Investigation of 3'-debenzoyl-3'-(3-([¹²⁴I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo.
A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3'-Debenzoyl-3'-(3-([(124)I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3'-debenzoyl-3'-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6h post-injection. However, at 6h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies.
Department of Nuclear Medicine, State University of New York, Buffalo, New York, USA. msajjad@buffalo.ed
M
M
Sajjad
U
U
Riaz
R
R
Yao
R J
RJ
Bernacki
M
M
Abouzied
D A
DA
Erb
N D
ND
Chaudhary
J M
JM
Veith
G I
GI
Georg
H A
HA
Nabi
D000818:Animals; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D019275:Radiopharmaceuticals; D017239:Paclitaxel