Analyses of Ferrous and Ferric State in DynabiTab Using Mössbauer Spectroscopy.

Antianemic medicament ferrous gluconate, ferrous fumarate, and a Dynabi tablet with a basic iron bearing ingredient were studied with the use of Mössbauer spectroscopy. Room temperature spectra of ferrous gluconate gave clear evidence that the two phases of iron were present: ferrous (Fe2+) as a major one with a contribution at and above 91 a.u.% and ferric (Fe3+) whose contribution was found to be ~9 a.u.%. In the case of ferrous fumarate, a single phase was measured corresponding to ferrous (Fe2+) state. A Dynabi tablet consists of ferrous fumarate and ferrous fumarate. The ferric phase in ferrous gluconate is able to be reached about ~3.6 a.u.% in a tablet.

Biological evaluation of (177)Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting.

Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with (177)Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10(6) cells. The radio-peptide slowly internalized, and 24.4±0.5% of the total binding was internalized in 4hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02±9.36 at 1.5hr p.i., and was increased to 216.33±61.58 at 24hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this (177)Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors.

Preclinical pharmacokinetic, biodistribution, imaging and therapeutic efficacy of (177)Lu-Labeled glycated bombesin analogue for gastrin-releasing peptide receptor-positive prostate tumor targeting.

UNLABELLED: The gastrin-releasing peptide receptor (GRPR) has been shown to be overexpressed in many human tumors, including prostate, colon, gastric, breast, pancreatic, and small cell lung cancers. Because bombesin (BBS) binds to GRPR with high affinity, BBS derivatives have been labeled with various radionuclides and have been demonstrated to be successful candidates for peptide receptor radiotherapy (PRRT). The present study describes the in vitro and in vivo preclinical characteristics of (177)Lu-DOTA-Lys(glucose)-4 aminobenzoic acid-BBS7-14 ((177)Lu-DOTA-gluBBN) to prepare radiolabeled candidates for the treatment of GRPR-expressing prostate tumors. METHODS: (177)Lu-DOTA-gluBBN was prepared as previously published [1]. Human prostate PC-3 tumor cells were used to determine the binding (Kd) retention and efflux of (177)Lu-DOTA-gluBBN. Pharmacokinetic, imaging, and radiotherapy studies were performed in PC-3 xenografted mice. RESULTS: The Kd value of (177)Lu-DOTA-gluBBN was 0.63 nM, with a maximum binding capacity (Bmax) of 669.7 fmol/10(6) cells (4.04×10(5) GRPR/cell). During a 2-hr incubation, 90.1±0.4% of the cell-associated radio-peptide was internalized, and 56.3±7.1% of the internalized radio-peptide was externalized in vitro. High amounts of the radio-peptide were rapidly accumulated in a PC-3 tumor in vivo, and the % ID/g of the tumor was 12.42±2.15 1 hr p.i. The radio-peptide was quickly cleared from the blood, yielding tumor-to-blood ratios of 39.22±17.36 at 1 hr p.i. and 330.67±131.23 at 24hr p.i. In addition, (177)Lu-DOTA-gluBBN was clearly visualized in PC-3 tumors 1 hr p.i. and significantly inhibited the tumor growth (P<0.05). Treatment-related toxicity in the pancreas and kidneys was not observed, except for slight glomerulopathy. CONCLUSIONS: The pharmacokinetic, imaging, and therapy studies suggest that this (177)Lu-DOTA-gluBBN has promising characteristics for application in nuclear medicine, namely, for the diagnosis and treatment of GRPR-overexpressing prostate tumors.

Synthesis and biological evaluation of a novel (177)Lu-DOTA-[Gly(3)-cyclized(Dap(4), (d)-Phe(7), Asp(10))-Arg(11)]α-MSH(3-13) analogue for melanocortin-1 receptor-positive tumor targeting.

In this study, a novel α-melanocyte stimulating hormone (α-MSH) analogue 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) coupled [Gly(3)-cyclized(Dap(4), (d)-Phe(7), Asp(10))-Arg(11)]α-MSH(3-13) (DOTA-GMSH) for melanocortin-1 receptor (MC-1R) targeting was newly synthesized, radiolabeled with (177)Lu, and in vitro and in vivo characterized. (177)Lu-labeled peptides were prepared with a high radiolabeling yield (>98%), and its Log p value was -2.89. No degradation was observed not only by serum incubation at 37°C for 7 days but also by an HPLC analysis of radioactive metabolites in urine. A cell binding assay revealed that an inhibitory concentration of 50% (IC(50)) of the peptide was 3.80 nM. The tumor-to-blood ratio, which was 14.27 at 2 hours p.i., was increased to 56.37 at 24 hours p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and was rapidly cleared from the blood pool. We, therefore, conclude that (177)Lu-DOTA-GMSH has promising characteristics for application in nuclear medicine, namely for the diagnosis of MC-1R over-expressing tumors.

Preparation and in-vivo evaluation of 99mTc-IOTIDA for cholescintigraphy.

The synthesis, radiolabeling and in vivo evaluation of 99mTc-IOIDA(3-iodo 2,4,6-trimethylpheyl carbamoylmethyl iminodiacetic acid) for the assessment of hepatocytic function and the functional status of the cystic duct and the gallbladder are described. For a scintigraphic imaging comparison, three different 99mTc-IDA derivatives, 99mTc-DISIDA, 99mTc-mebrofenin and 99mTc-IOTIDA, were prepared and evaluated for their in vivo pharmacokinetic behavior through animal studies. Serial static image scans of rabbits injected with 99mTc-IOTIDA revealed that none of the tissues except the hepatobiliary system showed radioactivity concentrations. A scintigraphic study in a healthy volunteer showed that most of the administrated radioactivity accumulated in the liver and was rapidly excreted through the hepatobiliary system, visualizing the gallbladder within 15 min. In conclusion, 99mTc-IOTIDA is a potential hepatobiliary imaging agent for the evaluation of the functional status of hepatocytes and the patency of the biliary duct.