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:Y. Zhao, C. Zhang, C. Qi, S. Feng, G. You, Z. Fu, F. Guo, and R. Wang
Two peptide ligands conjugated adenine, [9-N-(tritylmercapto acetyl diglycyl aminoethyl) adenine, Tr-MAG2-Ade] and [9-N-(tritylmercapto acetyl triglycyl aminoethyl) adenine, Tr-MAG3-Ade], are synthesized and labeled with 99mTc by directly labeling method. The stability of 99mTc-MAG2-adenine and 99mTc-MAG3-adenine in vitro is measured. The uptake radios of tumor to muscle at 3h post-injection are 5.70 and 4.92, respectively.
The biodistribution and scintigraphic imaging studies show that the two complexes have high localization in tumor and high
contrasted tumor images can be obtained, which suggest their potential utility as tumor imaging agents. But the high radioactivity
of abdomen could prevent the tumor imaging in this area.
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.
Metronidazole (MTNZ) is an antiprotozoa drug, could be labeled with the 99mTc. MTZL could be used as an ideal vehicle to deliver radioactive decay energy of 99mTc to the sites of tumor, thus facilitate tumor imaging. The process of labeling was done using tin chloride as reducing agent.
The optimum conditions required to label 25 μg MTZL were 100 μg stannous chloride, 30 min reaction time, room temperature
at pH 7–9 using 0.5 M phosphate buffer. The radiochemical purity of the labeled compound, at the above conditions, was determined
using paper chromatography. The yield was about 93%. About 2.5 × l06 of Ehrlich Ascites Carcinoma (EAC) was injected intrapritoneally (i.p) to produce ascites and intramuscularly (i.m) in the
right thigh to produce solid tumor in female mice. Biodistribution studies were carried out by injecting solution of 99mTc-MTZL in normal and tumor bearing mice. The uptake in ascites was over 5% of the injected dose per gram tissue body weight,
at 4 h post injection and above 4% in solid tumor. These data revealed localization of the tracer in the tumor tissues with
high percentage sufficient to use 99mTc MTZL as promising tool for diagnosis of tumor.
Authors:M. Motaleb, N. Al-Musayeib, W. Zaghary, and H. Shweeta
Shikonin was isolated from Ratanjot pigment then the obtained shikonin was well characterized. This study is aimed to optimize
radiolabeling yield of shikonin with 99mTc with respect to factors that affect the reaction conditions such as shikonin amount, SnCl2·2H2O amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it
was found to be stable for up to 6 h. Biodistribution studies showed that, 99mTc–shikonin accumulate in tumor sites with higher T/NT than other currently available 99mTc(CO)3-VIP, 99mTc–nitroimidazole analogues and 99mTc–polyamine analogues indicating that shikonin deliver 99mTc to the tumor sites with a percentage sufficient for imaging and can overcome many drawbacks of other radiopharmaceuticals
used for tumor imaging.
Authors:M. Barrio, M. Viaggi, M. Donaldson, P. Portela, L. Bover, J. Mordoh, and S. de Castiglia
A lyophilized one-step kit of Mab FC-5.01, reactive with human breast cancer and malignant melanomas, was formulated. A direct method based on the reduction of protein disulphide bridges using 2-mercaptoethanol was used with methylene diphosphonate as the transchelating ligand. The labeled species were analyzed by ITLC thin layer chromatography and high performance liquid chromatography. Labeling efficiency was greater than 90%. Immunoreactivity was assessed on IIB-BR-G cells. 99mTc-labeled Mab FC-5.01 biodistribution and tumor imaging were performed in nude mice bearing IIB-BR-G breast cancer xenografts. At 24 hs accumulation of 99mTc increased in tumor and decreased in blood and most organs in agreement with results of an in vitro cysteine challenge assay. Quality control tests demonstrated that the kit was stable for up to 120 days. Animal studies demonstrated good and specific in vivo tumor targeting.
Authors:T. Ertay, P. Unak, C. Tasci, F. Z. Biber, F. Zihnioglu, and H. Durak
The aim of this study was to label exorphin C with 99mTc and to examine its usefulness as opioid receptor binding radiopharmaceutical in Albino Wistar rats. Exorphin C, which is a peptide with 5 aminoacids, was labeled with 99mTc using glucoheptonate (GH) as a bifunctional chelating agent. Labeling efficiency was higher than 98%. The compound was stable for at least 5 hours at room temperature. Mammary tumor bearing Albino Wistar rats were imaged using gamma-camera. Biodistribution studies were also performed. Results demonstrated that 99mTc-glucoheptonate-exorphin C (99mTc-GE) analogs may be useful as a new class of receptor-binding peptides for the diagnosis and therapy of some cancer diseases related with opioid receptor-expressing tissues.
Authors:Ashok Behera, Kakali De, Susmita Chandra, Sankha Chattopadhyay, and Mridula Misra
In vivo imaging of tumours using radiolabelled somatostatin (SST) analogues has become an accepted clinical tool in oncology.
HYNIC-Tyr3 octreotide and Tyr3 octreotide were synthesized by FMOC solid-phase peptide synthesis using a semi-automated synthesizer. These were analyzed
and purified by RP-HPLC, mass spectroscopy, IR spectroscopy, 1H NMR and 13C NMR. The prochelator 6-BOC-HYNIC was also synthesised and characterised indigenously. HYNIC-Tyr3 octreotide was labelled with 99mTc using Tricine and EDDA as coligand by SnCl2 method. Labelling with 99mTc was performed at 100 °C for 15 min and radiochemical analysis by ITLC and HPLC methods. The radiochemical purity of the
complex was over 98% and log p value was found to be −1.27 ± 0.12. The stability of radiolabelled peptide complex was checked at 37 °C up to 24 h. Blood
clearance and protein-binding study was also performed. In vivo biodistribution studies in rat showed uptake of 99mTc-HYNIC-TOC in kidney than any other organs. The blood clearance was faster with rapid excretion through kidneys and relatively
low uptake in liver.
Authors:Zhang Jinming, Tian Jiahe, Wang Wushang, and Liu Baoli
[11C]-choline has been reported as a potential tracer for imaging a variety of human tumors with positron emission tomography
(PET). A new labeling technique for [11C]-choline was established depending on parameters optimized, such as reaction time, volume, temperature, and the quantity
of DMAE.The synthesis yield was improved from 82.0% to 96.5% (EOB), while the consumption of DMAE precursor decreased from
60 to 2 mg. Absolute yield of [11C]-choline was 2500 MBq for a 10-minute irradiation at15mA, and a total synthesis time of less than 8 minutes from [11C]-CH3I to [11C]-choline.
Authors:N. Sadeghzadeh, M. Gandomkar, R. Najafi, M. Shafiei, S. Sadat Ebrahimi, A. Shafiee, and B. Larijani
A variety of human tumors like prostate and breast cancer express bombesin receptors. Due to this a new bombesin analogue
was labeled with 99mTc via HYNIC and tricine as a coligand and investigated further. Peptide was synthesized on a solid phase using Fmoc strategy.
Labeling with 99mTc was performed at 100 °C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide
was checked in the presence of human serum at 37 °C up to 24 h. Internalization was studied with the human GRP receptor cell
line PC-3. The biodistribution was studied in mice. Labeling yield of >98% was obtained corresponding to a specific activity
of ~80.9 GBq/μmol. Radiopeptide internalization into PC-3 cells was moderate and specific (10.7 ± 1.2% at 4 h). A high and
specific GRP receptor expressing mouse tumor and pancreas uptake (1.12 ± 0.08 and 1.04 ± 0.11% ID/g after 1 h respectively)
was also determined.