Technetium-99 m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo

Abstract

The high incidence and mortality of breast cancer supports efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of tumor treatments while concurrently and selectively delivering anticancer agents to the cancer tissue. In the present study we described the preparation of technetium–99 m (99mTc)-labeled paclitaxel (PTX) and evaluated its feasibility as a radiotracer for breast tumors (4T1) in BALB/c mice. Thin Layer Chromatography (TLC) was used to determine the radiochemical purity and in vitro stability of 99mTc-PTX. PTX micelles showed a unimodal distribution with mean diameter of 13.46 ± 0.06 nm. High radiochemical purity (95.8 ± 0.3%) and in vitro stability (over than 95%), up to 24 h, were observed. Blood circulation time of 99mTc-PTX was determined in healthy BALB/c mice. 99mTc-PTX decays in a one-phase manner with a half-life of 464.3 minutes. Scintigraphic images and biodistribution were evaluated at 4, 8 and 24 h after administration of 99mTc-PTX in 4T1 tumor-bearing mice. The data showed a significant uptake in the liver, spleen and kidneys, due to the importance of these routes for excretion. Moreover, high tumor uptake was achieved, indicated by high tumor-to-muscle ratios. These findings indicate the usefulness of 99mTc-PTX as a radiotracer to identify 4T1 tumor in animal models. In addition, 99mTc-PTX might be used to follow-up treatment protocols in research, being able to provide information about tumor progression after therapy.

Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study

“…Paclitaxel (PTX) is one of the most effective and potent antitumor drugs used in clinical oncology against a wide range of solid tumors, including metastatic breast cancer [6,8,10,26,28]. However, its low specificity can lead to an increased systemic toxicity, since the drug can act indiscriminately in tumor and healthy tissues.…”

“…99m Tc-PTX was prepared using the methodology described by Monteiro et al [14,26] and was used as a comparative group with the liposomal preparations presented in these studies [3,16]. For liposome radiolabeling, the lipid DSPE-PEG 2000 -DTPA was used since it is well known that 99m Tc generates a stable complex with chelating agents, such as DTPA, for image purposes [23,41,43,44].…”

“…The results showed a high radiochemical purity and stability (over to 90%), up to 24 h after radiolabeling. Radiochemical purity above 90% is required since the presence of high amount of impurities leads to poor image quality, which might result in a biodistribution profile that no longer reflects the nanoparticle behavior [26,45]. …”

“…An aliquot of 0.1 ml of Na 99m TcO 4 (37 MBq) was then added and the mixture was kept at room temperature for 15 min 99m Tc-PTX was prepared as reported by Monteiro et al and it was used in this study as a comparative group with the liposomal preparations presented in this paper [26]. …”

Analysis of anticancer drugs using thin layer chromatography- A review

“…The samples were analyzed by using ascending instant TLC [52]. Recently, Monteiro et al developed 99m Tc-labeled paclitaxel and used a TLC method to evaluate the radiochemical purity and in vitro stability of 99m Tc-paclitaxel in saline and murine plasma [53].…”