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.

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.

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 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.