The Radiolabeling of [161Tb]-PSMA-617 by a Novel Radiolabeling Method and Preclinical Evaluation by In Vitro/In Vivo Methods.

Background: Prostate cancer (PC) is the most common type of cancer in elderly men, with a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently, [161Tb], a radiolanthanide introduced for treating micrometastatic foci, has shown great promise for treating prostate cancer. Results: In this study, Terbium-161 [161Tb]Tb was radiolabeled with prostate-specific membrane antigen (PSMA)-617 ([161Tb]-PSMA-617) and the therapeutic efficacy of the radiolabeled compound investigated in vitro and in vivo. [161Tb]-PSMA-617 was found to have a radiochemical yield of 97.99 ± 2.01% and was hydrophilic. [161Tb]-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 hours. In vitro, [161Tb]-PSMA-617 showed a cytotoxic effect on LNCaP cells but not on PC-3 cells. In vivo, scintigraphy imaging visualized the accumulation of [161Tb]-PSMA-617 in the prostate, kidneys, and bladder. Conclusions: The results suggest that [161Tb]-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer.

Investigation of Bioactivity of Estragole Isolated from Basil Plant on Brain Cancer Cell Lines Using Nuclear Method.

BACKGROUND: In recent years, there has been a significant increase in studies investigating the potential use of plant-origin products in the treatment and diagnosis of different types of cancer. METHODS: In this study, Estragole (EST) was isolated from basil leaves via ethanolic extraction using an 80% ethanol concentration. The isolation process was performed using the High Performance Liquid Chromatography (HPLC) method. The EST isolated from the basil plant was radiolabeled with 131I using the iodogen method. Quality control studies of the radiolabeled EST (131IEST) were carried out by using Thin Layer Radio Chromatography (TLRC). Next, in vitro cell, culture studies were done to investigate the bio-affinity of plant-originated EST labeled with 131I on human medulloblastoma (DAOY) and human glioblastoma-astrocytoma (U-87 MG) cell lines. Finally, the cytotoxicity of EST was determined, and cell uptake of 131I-EST was investigated on cancer cell lines by incorporation studies. RESULTS: As a result of these studies, it has been shown that 131I-EST has a significant uptake on the brain cells. CONCLUSION: This result is very satisfying, and it has encouraged us to do in vivo studies for the molecule in the future.

A novel radiolabeled graft polymer: Investigation of the radiopharmaceutical potential using Albino Wistar rats.

Fe3O4 magnetic graft-Lys-poly(HEMA) was synthesized, labeled with 99mTc for the first time and its radiopharmaceutical potential was investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography. The labeling yield of radiolabeled polymer was found to be about 100%. Then, stability and lipophilicity were determined. The lipophilicity of 99mTc labeled Fe3O4 graft-Lys-poly(HEMA) was found to be 3.77. The serum stability experiments demonstrated that approximately 100% of radiolabeled polymer existed as an intact complex in the rat serum within 240 min. Biodistribution of radiolabeled magnetic graft-Lys-poly(HEMA) was performed on female Albino Wistar rats by scintigraphy and biodistribution studies. High uptake was seen in the stomach, the pancreas, brain, ovarian, intestines and the breast.

Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

INTRODUCTION: In this study, novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (99mTc-ISboroxime-N3: R=IS; 99mTc-MPboroxime-N3: R=MP; 99mTc-PAboroxime-N3: R=PA; 99mTc-PYboroxime-N3: R=PY; and 99mTc-Uboroxime-N3: R=5U) were evaluated as heart imaging agents. METHODS: Complexes [99mTc(N3)(CDO)(CDOH)2B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN3 and [99mTcCl(CDO)(CDOH)2B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention. RESULTS: 99mTc-ISboroxime-N3, 99mTc-PYboroxime-N3 and 99mTc-Uboroxime-N3 were prepared with high RCP (93-98%) while the RCP of 99mTc-MPboroxime-N3 and 99mTc-PAboroxime-N3 was 80-85%. The myocardial retention curves of 99mTc-ISboroxime-N3, 99mTc-PYboroxime-N3 and 99mTc-Uboroxime-N3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99mTc-ISboroxime-N3, 0.7±0.1min for 99mTc-PYboroxime-N3 and 0.9±0.4min for 99mTc-Uboroxime-N3. The 2-min heart uptake from biodistribution studies followed the ranking order of 99mTc-ISboroxime-N3 (3.60±0.68%ID/g)>99mTc-PYboroxime-N3 (2.35±0.37%ID/g)≫99mTc-Uboroxime-N3 (1.29±0.06%ID/g). 99mTc-ISboroxime-N3 had the highest 2-min heart uptake among 99mTc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for 99mTc-ISboroxime-N3. CONCLUSION: Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [99mTc(N3)(CDO)(CDOH)2B-R]. Among the radiotracers evaluated in SD rats, 99mTc-ISboroxime-N3 has the highest initial heart uptake with the heart retention comparable to that of 99mTc-Teboroxime. 99mTc-ISboroxime-N3 is a promising alternative to 99mTc-Teboroxime for SPECT MPI.

Radiolabeling of new generation magnetic poly(HEMA-MAPA) nanoparticles with (131) I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats.

In this study, N-methacryloyl-l-phenylalanine (MAPA) containing poly(2-hydroxyethylmethacrylate) (HEMA)-based magnetic poly(HEMA-MAPA) nanobeads [mag-poly(HEMA-MAPA)] were radiolabeled with (131) I [(131) I-mag-poly(HEMA-MAPA)], and the radiopharmaceutical potential of (131) I-mag-poly(HEMA-MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that (131) I binded to mag-poly(HEMA-MAPA) efficiently. In this sense, binding yield of (131) I-mag-poly(HEMA-MAPA) was found to be about 95-100%. In addition to this, optimum radiodination conditions for (131) I-mag-poly(HEMA-MAPA) were determined by thin-layer radiochromatography studies. In addition to thin-layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for (131) I-mag-poly(HEMA-MAPA) were realized. It was determined that lipophilicities of mag-poly(HEMA-MAPA) and (131) I-mag-poly(HEMA-MAPA) were 0.12 ± 0.01 and 1.79 ± 0.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440 min. It was found that (131) I-mag-poly(HEMA-MAPA) existed as a stable complex in rat serum within 60 min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important (131) I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results.

Investigation of therapeutic efficiency of bleomycin and bleomycin-glucuronide labeled with (131)I on the cancer cell lines.

The aim of this study is to determine the incorporations of radiolabeled bleomycin ((131)I-BLM) and bleomycin-glucuronide ((131)I-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with (131)I, quality control studies were done and the incorporation yields of (131)I-BLM and (131)I-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for (131)I-BLM and (131)I-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that (131)I-BLM and (131)I-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of (131)I-BLMGLU was higher than that (131)I-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of (131)I-BLMGLU on the four cell lines were about five to six times higher than (131)I-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the ß-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells.

Radiolabeling of bleomycin-glucuronide with (131)I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice.

Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.

Metabolic comparison of radiolabeled bleomycin and bleomycin-glucuronide labeled with 99mTc.

The metabolic comparison of bleomycin (BLM) and bleomycin-glucuronide (BLMG) radiolabeled with (99m)Tc ((99m)Tc-BLM and (99m)Tc-BLMG, respectively) has been investigated in this study. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. To compare the metabolic behavior of BLM and its glucuronide conjugate radiolabeled with (99m)Tc, scintigraphic, and biodistributional techniques were applied using male New Zealand rabbits and Albino Wistar rats. The results obtained have shown that these compounds were successfully radiolabeled with a labeling yield of about 100%. Maximum uptakes of (99m)Tc-BLM and (99m)Tc-BLMG metabolized as N-glucuronide were observed within 2 hours in the liver, the bladder, and the spinal cord for (99m)Tc-BLM and the lung, the liver, the kidney, the large intestine, and the spinal cord for (99m)Tc-BLMG, respectively. Scintigraphy and biodistributional studies performed on the experimental animals have shown that radiopharmaceutical potentials of these compounds are completely different. At the same time, uptake of the (99m)Tc-BLMG was found to be better than that of (99m)Tc-BLM.

Metabolic comparison of radiolabeled aniline- and phenol-phthaleins with (131)I.

The metabolic comparison of aniline- and phenol-phthaleins radiolabeled with (131)I ((131)I-APH and (131)I-PPH, respectively) has been investigated in this study. To compare the metabolic behavior of these phthaleins and their glucuronide conjugates radiolabeled with (131)I, scintigraphic and biodistributional techniques were applied using male Albino rabbits. The results obtained have shown that these compounds were successfully radioiodinated with a radioiodination yield of about 100%. Maximum uptakes of (131)I-APH and (131)I-PPH, which were metabolized as N- and O-glucuronides, were observed within 2 h in the bladder and in the small intestine, respectively. In the case of verification of considerably up taking of these compounds also by tumors developed in the small intestine and in the bladder tissues, these results can be expected to be encouraging to test these compounds, which will be radiolabeled with other radioiodines such as (125)I, (123)I and (124)I as imaging and therapeutic agents in nuclear medical applications.

Transfer of orally administrated iodine-131 into chicken eggs.

Radioactive iodine-131 as both as free iodide (Na131I) and covalently bound to aniline (aniline-131I) was added to the drinking water of two Leghorn laying hens as a single dose and also as a cumulative dose over 1 week. The radioactivity of the principal parts of the eggs, i.e. shell, white, and yolk, was measured, and the radioactivity levels per gram material, and percent of the total radioactivity were calculated. The radioactivity measurements were continued for 1 month following the administration of 131I. In the case of the single dose administration, the results obtained showed that about 15% of the total radioactivity administered as Na131I was transported into the egg structure; compared to only about 1% for aniline-131I. After cumulative administration, about 15% of the total administered radioactivity was transported into the egg structure with both forms of 131I. This was probably because of metabolic cleavage of iodine bonds in the labeled aniline molecules during the longer period of exposure. These results also showed considerable accumulation of 131I in the egg yolks. In the case of the single dose administration, 131I can be detected in eggs up to about 20 days after administration, and up to about 30 days, in the case of the cumulative administration over 1 week.