title: Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats.
abstract: The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.
authors: Division of Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors: T
authors: T
authors: Higuchi
authors: D J
authors: DJ
authors: Yang
authors: S
authors: S
authors: Ilgan
authors: L W
authors: LW
authors: Tansey
authors: F
authors: F
authors: Zareneyrizi
authors: T
authors: T
authors: Inoue
authors: K
authors: K
authors: Endo
authors: E E
authors: EE
authors: Kim
authors: D A
authors: DA
authors: Podoloff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001345:Autoradiography; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D007205:Indium Radioisotopes; D020128:Inhibitory Concentration 50; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007205:Indium Radioisotopes; C119052:indium DTPA-adriamycin; D004369:Pentetic Acid; D004317:Doxorubicin