The aim of this study is to examine biological behaviour of radiolabeled guanine with [Tc(CO)3]+ core in vitro and in vivo. In vitro biological behavior of 99mTc(CO)3–Gua was evaluated on Lung (A-549), Breast (MCF-7), Colonic (Caco) carcinoma cell lines and normal human bronchial epithelial
(NHBE). 99mTc(CO)3–Gua compound showed high uptake on A-549 cell line when compared to NHBE cell line. Biodistribution characteristics of 99mTc(CO)3–Gua was evaluated using New Zeland Rabbits. Scintigraphic results showed that a high level of radioactivity was observed
in the lungs and liver shortly after administration of the 99mTc(CO)3–Gua and excretion takes place via both renal and hepatobiliary route. It was concluded that 99mTc(CO)3–Gua could be used as a nucleotide radiopharmaceutical for imaging purposes.
This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of the 99mTc(CO)3–AOPA colchicine conjugate. The novel ligand was successfully synthesized by conjugation of N-(acetyloxy)-2-picolylamino (AOPA) to deacetylcolchicine via a short carbonyl-methylene linker. Radiolabeling was performed
in high yield with [99mTc(CO)3]+ core. 99mTc(CO)3–AOPA colchicine conjugate was hydrophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice
showed that 99mTc(CO)3–AOPA colchicine conjugate accumulated in the tumor with good uptake and retention. However, its clearance from normal organs
was not so fast, resulting in poor T/NT ratios. Further modification on the linker or/and 99mTc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.
Authors:Drishty Satpati, Archana Mukherjee, Meera Venkatesh, and Sharmila Banerjee
The over-expression of folate receptors in variety of neoplastic tissues makes radiolabeled folate conjugates potential agents
for imaging and therapy of such cancers. With the aim of preparing an imaging agent for targeting folate receptors, folic
acid has been conjugated with homocysteine for complexation with [99mTc(CO)3(H2O)3]+ core. The radiolabeled complex of the homocysteine-folate could be obtained in >95% radiochemical yield as observed by HPLC.
Stability of complex in saline was studied and challenge studies with histidine and cysteine revealed kinetic stability of
the complex. Lipophilicity of the radiolabeled complex (log P) was found to be 0.45. In vitro uptake of 99mTc(CO)3-labeled folic acid derivative was studied in KB cells and inhibition studies were carried out using 3H-folic acid and cold homocysteine–folate conjugate. The in vitro studies indicated loss of binding affinity of the derivative
towards folate receptors.
In the current investigation tosufloxacin (TSN) was derivatized to its dithiocarbamate (TSND) derivative and its radiolabeling
with technetium-99m using [99mTc(CO)3(H2O)3]+ precursor. The labeled TSND (99mTc(CO)3-TSND) was radiochemically characterized in saline and serum and biologically its in vitro binding with Proteus mirabilis (P. mirabilis) and biodistribution in male Wister rats (MWR) artificially infected with live and heat killed P. mirabilis. Radiochemically a stable radio-tricarbonyl TSND complex was observed with a maximum stability of 98.15 ± 0.32% and it remained
more than 90% up to 4 h after reconstitution. The stability decreased to 91.00 ± 0.30% from 98.15 ± 0.32% within 4 h. In serum
at 37 °C the growth of some unwanted side product decreased the stability by 15.65% within 16 h. The complex showed saturated
in vitro binding with P. mirabilis up to 78.50% (90 min). In MWR infected with live P. mirabilis the percent (%) uptake of the complex in blood, liver, spleen, stomach, intestines and kidneys were almost similar to the
MWR infected with heat killed. However, the % accumulation of the complex in the infected muscle was six times higher than
in the inflamed and normal muscle in MWR infected with live P. mirabilis. On the basis of immovability of the 99mTc(CO)3-TSND complex in normal saline, in vitro permanence in serum, saturated in vitro binding with P. mirabilis and six fold uptake in the infected muscle of the MWR infected with live P. mirabilis as compared to the normal muscle, the suitability of the 99mTc(CO)3-TSND complex is established as a promising infection radiotracer.
Mixed ligand fac-tricarbonyl complex of [99mTc(CO)3-DMSA-MIBI] has been prepared starting from the precursor [99mTc(OH2)3(CO)3]+. The complex can be obtained in good yield and purity in a two-step procedure by first attaching meso-2,3-dimercaptosuccinic acid (DMSA, HOOCCH(SH)CH(SH)COOH) with [99mTc(OH2)3(CO)3]+, followed by addition of MIBI [tetrakis-2-methoxyisobutylisonitrile (CH3OC(CH3)2CH2-N≡C) copper(I) tetrafluoroborate] solution. The complex was characterized by TLC and HPLC and was studied by means of octanol-water
partition coefficient, electrophoresis, stability in vitro, and normal mice experiment. Biodistribution in mice demonstrated
that the complex showed higher myocardial uptake after 0.5-hour p.i. The ratios of heart/liver (%ID/g) in the case of 99mTc(CO)3-DMSA-MIBI was higher (1.88) than that observed in case of 99mTc-MIBI1 (0.93) after 0.5-hour p.i. (P<0.05). Results showed that the complex may be developed to a novel myocardial perfusion-imaging agent.
This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of [99mTc(CO)3(IDA–PEG3–CB)]−. The novel chlorambucil derivative was successfully synthesized by conjugation of iminodiacetic acid (IDA) to chlorambucil
via a pegylated linker. The ligand could be labeled by [99mTc(CO)3]+ core in high yield to get [99mTc(CO)3(IDA–PEG3–CB)]−, which was very hydrophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that
[99mTc(CO)3(IDA–PEG3–CB)]− accumulated in the tumor with favorable uptake and retention. The good accumulation in tumor tissue with high tumor/muscle
ratios warrants further research to improve tumor targeting efficacy and pharmacokinetic profile of radiolabeled chlorambucil
derivative by structural modification.
This study reports the synthesis, radiolabeling and preliminary biodistribution results of [99mTc(CO)3(MN-TZ-BPA)]+ in tumor-bearing mice. The novel nitroimidazole derivative was successfully synthesized by conjugation of bis(pyridin-2-ylmethyl)amine
(BPA) to 2-methyl-5-niroimidazole via “click” reaction. The ligand could be labeled by [99mTc(CO)3]+ core in high yield to get [99mTc(CO)3(MN-TZ-BPA)]+, which was very hydrophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that
[99mTc(CO)3(MN-TZ-BPA)]+ accumulated in the tumor with certain initial uptake while poor retention. The rapid clearance from normal organs with favorable
tumor/muscle ratios warrants further research to improve tumor targeting efficacy and pharmacokinetic profile of radiolabeled
nitroimidazoles by structural modification.
Authors:D. Djokić, D. Janković, Lj. Stamenković, and I. Pirmettis
The confirmation that N-substituted imidodiacetic acids, as small and simple ligand systems containing amines and carboxylic
acids, could be coordinated to the tricarbonyl core and form inert complexes with [99mTc (CO)3(H2O)3]+, is demonstrated. The HPLC quality control results of 99mTc-carbonyl tagged IDA molecules, performed by gradient HPLC, have shown that HIDA, EHIDA and p-butyl-IDA form complexes with
[99mTc(CO)3(H2O)3]+, with a labeling yield of ~90% for each of 99mTc(CO)3 IDA derivatives. However, the changes in the structure of labeled compounds, e.g., EHIDA, influence the changes in the biological
behavior. In comparison with 99mTc-EHIDA, the biliary excretion of 99mTc(CO)3 EHIDA was lower, but the urinary excretion higher.
The mass production and extensive applications of nanomaterials may have potential negative effects on health of human beings.
Research on the in vivo behavior of fullerene, the most representative nanomaterial, just begins. In order to investigate
the in vivo behavior of fullerene derivative and to explore new biomedical application of fullerene, fullerol, C60(OH)20, was labeled by 99mTc(CO)3. The labeling conditions were optimized. Gamma counter and SPECT were used to access the in vivo biological behavior of the
complex. Results showed that the complex was stable in mice body. The complex was delivered to all tissues rapidly except
for brain. A significant percentage of total activity was retained in 3 h, particularly in the liver, spleen, lung, thyroid,
kidney and bladder, which indicated the mononuclear phagocyte system (MPS) took an important part in clearing the complex
and the complex was mainly excreted through urine. The low radioactivity of all tissues and organs in 24 h indicated that
the cleanup speed was rapid. The high uptake and rapid cleanup speed of the complex in important organs hinted fullerene could
be used as carrier for in vivo radionuclide decorporation agents.
Radio-complexation of sitafloxacin dithiocarbamate (SFDE) with technetium-99m (99mTc) using [99mTc(OH2)3(CO)3]+ precursor was investigated and compared with the 99mTc labeled SFDE prepared through 99mTcN core. The 99mTc(CO)3–SFDE radiocomlpex was assessed in terms of radiochemical purity (RCP), eternalness in serum, in vitro binding with Staphylococcus aureus (S. aureus) and biodistribution in artificially Staphylococcus aureus infected rats (SAIR). The feasibility of the 99mTc(CO)3–SFDE radiocomplex as a suitable S. aureus infection radiotracer was evaluated in SAIR. The complex showed maximum RCP of 98.45 ± 0.21% in saline and was remained tagged
more than 90% up to 4 h. The complex was found stable in serum and after 16 h only 17.95% de-tagged radio-fractions was observed.
Similar saturated in vitro binding behaviour was observed for both the radiocomplexes (99mTc(CO)3–SFDE and 99mTcN–SFDE) with living S. aureus. Both the radiocomplexes showed almost similar in vivo biodistribution in SAIR. Significantly higher but similar infected
to normal muscle ratio was observed for both the radiocomplexes in SAIR. The results of radiochemical purity (RCP), eternalness
in serum, in vitro binding and in vivo biodistribution in SAIR posed the 99mTc(CO)3–SFDE radiocomplex as suitable S. aureus infection radiotracer.