Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma: an open-label Phase II feasibility study

Sorafenib is considered a standard of care in advanced hepatocellular carcinoma [HCC]. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile may prove beneficial in advanced HCC. The primary objective was to evaluate the efficacy and safety of a sorafenib and gemcitabine combination in patients with advanced HCC. This was a non-randomized, open-label, single-arm, multi-centric Phase II study conducted in Pakistan where 30 treatment-naive patients aged between 26 and 73 years with Child-Pugh score A or B were treated with sorafenib [400 mg oral] twice daily for 16 weeks along with gemcitabine [1000 mg/m[2] intravenous] administered on day 1 and day 8 of a four-week cycle for 16 weeks. Of the 18 patients [60%] who completed all four cycles of treatment, eight patients had stable disease, two had partial response, and eight had progressive disease. There was no complete response. The most common [>/= 10% patients] treatment-emergent adverse events were gemcitabine-related thrombocytopenia [40%] followed by sorafenib-related hand-foot skin reaction and anorexia [33% each]. The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.

Development of [99m]Tc-5-fluorouracil as a potential tumor diagnostic agent

5-Fluorouracil is a well know drug for chemotherapy of various types of cancer. In the present study, we radiolabeled 5-fluorouracil with 99mTc for a diagnostic study of cancer. After successful labeling of the drug we performed an animal study to evaluate the potential of this radiopharmaceutical as a tumor diagnostic agent. The results showed 98.1 +/- 1.2 % labeling efficacy of 5-fluorouracil with [99m]Tc. The in vitro stability of the radiolabeled drug at room temperature at 4 hr of post-labeling was >96.5 +/- 0.4 %. The binding of the radiolabeled drug with plasma proteins was 66.6 +/- 3%. Partition coefficient results showed that this drug is hydrophilic in nature. Biodistribution study in rabbit models displayed faint uptake in liver. Both kidney and bladder were prominent as excretory route of the labeled drug. Bioevaluation was performed in Swiss Webster mice having naturally developed tumor. Mice were dissected, uptake of drug in various organs was studied and results showed prominent uptake in liver and tumor. Tumor was further investigated by histopathological study

Synthesis, characterization and bioevaluation of technetium-99m labeled N-[2-Hydroxybenzyl]-2-amino-2-deoxy-D-glucose as a tumor imaging agent

N-[2-Hydroxybenzyl]-2-amino-2-deoxy-D-glucose [NHADG] was synthesized by conjugation of salicylaldehyde to glucosamine. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m [[99m]Tc] in pertechnetate form [[99m]TcO4[-]] was carried out via chelation reaction in the presence of stannous chloride dihydrate. Maximum radiochemical yield of [99m]Tc-NHADG complex [99%] was obtained by using 1 mg NHADG, 200 micro g SnCl[2].2H[2]O, at pH 9.5 and reaction time of 15 min. The radiochemical purity of the [99m]Tc-NHADG complex was measured by Instant Thin Layer Chromatography [ITLC] and Paper Chromatography [PC], without any notable decomposition at room temperature over a period of 4h. The biological evaluation results show that the [99m]Tc labeled NHADG conjugate is able to specifically target mammary carcinoma in mice models, thus highlighting its potential as an effective [99m]Tc labeled glucose-derived agent for tumor imaging

In house development of [99m]Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection

In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography [PC]. The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 +/- 3.26 % particles of size less than 20nm [suitable for lymphoscintigraphy] were radiolabeled. [99m]Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 +/- 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 +/- 1.3 % radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared [99m]Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that [99m]Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice