Preparation and pharmacological evaluation of a new radiopharmaceutical, technetium-99m-5-fluorouracil, for tumor scintigraphy.
5-fluorouracil (5-FU) has been used for cancer chemotherapy since more than four decades. There are reports of use of (18)F and (19)F analogues of 5-FU for tumor studies using PET and NMR respectively. However, study pertaining to its use in g-scintigraphy is still lacking. In the present study, we have optimized the methodology to radiolabel it with technetium-99m ((99m)Tc) efficiently and evaluated its physicochemical and biological properties.


METHODS
5-FU was radiolabeled with (99m)Tc and evaluated for physicochemical properties. Blood kinetics were studied in rabbits and biodistribution was carried out in normal as well as tumor bearing mice. In vivo and in vitro tumor uptake of the radiocomplex was evaluated in Ehrlich Ascites Tumor (EAT) bearing mice and human breast cancer cell line (MDA-MB-468).


RESULTS
The resultant radiopharmaceutical ((99m)Tc-5-FU) has been found to be stable up to 24 h in both in vitro normal and physiological conditions. The blood clearance of the (99m)Tc-5-FU showed a bi-phasic pattern. High extraction of (99m)Tc-5-FU by the liver (36.41+/-2.79% of injected dose/g tissue) has been observed in mice, along with time dependent increase in the solid tumor to muscle ratio (2:1) measured at 4 h. Incubation of the radiocomplex with human breast cancer cells lines also showed time dependent increase in the uptake of the tracer.


CONCLUSIONS
It can be concluded that the (99m)Tc-5-FU possesses selectivity towards solid tumor tissue.
Kumar
Santosh
S
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, India.
Kumar Mishra
Anil
A
Chhikara
Bhupender S
BS
Chuttani
Krishna
K
Kumar Sharma
Rakesh
R
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C532874:technetium 99m 5-fluorouracil; D005472:Fluorouracil