Radiolabeling of benzylpenicillin with lutetium-177: Quality control and biodistribution study to develop theranostic infection imaging agent.

Benzylpenicillin acts through binding with beta-lactamase enzyme and inhibiting the bacterial cell wall biosynthesis. Therefore, the radiolabeling of benzylpenicillin with lutetium-177 is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiolabeling of benzylpenicillin resulted ~93% radiochemical yield at optimized reaction conditions. Radiochemical purity analysis was tested with the help of Whatman No. 2 paper and instant thin layer chromatography. Biodistribution study with healthy New Zeeland white rabbit revealed moderate accumulation in different organs. Kidneys are the major organs, showed not more than 4.57±0.89% injected dose per gram organ (ID/gm organ) at 1 h time point and 3.48±1.11% ID/gm organ at 6 h time point. The accumulation of tracer agent in liver was found in the range of 7.42±2.42% to 9.09±2.76 ID/gm organ. The glomerular filtration rate studies revealed rapid clearance - omitting the chance of nephrotoxicity. The radiolabeling yield, biodistribution and glomerular filtration rate results revealed 177Lu-benzylpencillin could be a potential candidate to diagnose the deep-seated bacterial infection.

99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

The radiolabeled drug 99m Tc-tazobactam (99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues.

(177) Lu-5-Fluorouracil a potential theranostic radiopharmaceutical: radiosynthesis, quality control, biodistribution, and scintigraphy.

The aim of this study is to develop (177) Lu-5-Flourouracil as a potential cancer therapeutic radiopharmaceutical. 5-Flourouracil (5-FU) is widely accepted as an anticancer drug of broad spectrum fame. The labeling of 5-FU was carried out at different set of experimental conditions using high specific activity of (177) LuCl3 . The optimum conditions for maximum radiochemical yield was set: 5-FU (5 mg), (177) LuCl3 (185 MBq), diethylenetriaminepentaacetic acid (10 µg), reaction volume (2 mL), pH (5.5), temperature (80°C), and reaction time (20 min). The radiochemical labeling was assessed with Whatman No. 2 paper, instant thin layer chromatographic, and radio-HPLC, which revealed >94% labeling results with sufficient stability up to 6 h. Serum stability study also showed (177) Lu-5-FU promising stability. Biodistribution study in normal rats and rabbits showed liver, stomach, kidney, and heart as area of increased tracer accumulation just after injection, which decreased to 1.4%, 0.4%, 0.2%, and 0.39% ID/g, respectively, after 72 h. Glomerular filtration rate and cytotoxicity study results of (177) Lu-5-FU showed it had no adverse effect on renal function and nontoxic to blood cells. The promising characteristics of (177) Lu-5-FU, that is, clever elimination from kidney and nontoxic nature toward blood cells make it the radiopharmaceutical for further testing in patients for therapeutic purposes.