Radiolabeling and preclinical animal model evaluation of DTPA coupled 99mTc-labelled flutamide complex ([99mTc]DTPA-FLUT) as a potential radiotracer for cancer imaging.

BACKGROUND: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. PURPOSE: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185 MBq freshly eluted 99mTcO4-1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. RESULTS: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [99mTc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [99mTc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. CONCLUSION: Stable, newly developed [99mTc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.

Synthesis of 99m Tc-roxithromycin: A novel diagnostic agent to discriminate between septic and aseptic inflammation.

Roxithromycin is a second-generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium-99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3-0.5 mg ligand, 2-6 µg SnCl2 ·2H2 O as a reducing agent at basic pH (8-10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq 99m Tc added into the reaction vials and incubated for a wide range of temperature (-4 to 65°C). The percent radiochemical purity of 99m Tc-roxithromycin was assessed with the help of the radio-thin-layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio-HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat-killed Staphylococcus aureus) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that 99m Tc-roxithromycin (99m Tc-ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that 99m Tc-ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage.