Current Radiopharmaceuticals - Volume 6, Issue 3, 2013

The role of copper in the metabolism of human cancer cells has been largely investigated in the last 20 years and a strong relationship between copper levels and cancer progression has been demonstrated. Moreover copper is involved in tumor angiogenesis as well as in non-neoplastic conditions like neurodegenerative diseases. The main mechanism of action is related to a cellular transporter (CTR1) that plays a pivotal role in preserving the intra-cellular homeostasis, allowing at the same time the anti- tumor activity of platinum based therapies. Copper-64, emitting positrons and β- radiations, is suitable for the labeling of a large number of molecules that could be used for radionuclide imaging, being also usable in radionuclide therapy. Nevertheless few data are at present available on radiotracers labeled with radiocopper and in particular on the use of 64Cu-Cl2 in cancer patients. In this paper we analyze the potential applications for Copper-64 as PET agent in the clinical oncological scenario.

Target and purpose: Cancer and heart disease are hard maladies in human communities. To recognize these kinds of diseases in primary states can help for remission and decreasing the expenses. One of the best techniques for recognizing is imaging of the tissue. Methods: The main reason of this study is to survey the design of molecules Gd3+ - Defrasirox - DG as a type of glucose labeled with gadolinium to capture more specific cancer tissue and heart by MRI instrument as a technique extremely accurate and sensitive not too costly and lack of radioactive half-life compared with radioactive 18FDGas competing compound. Result: In this research, glucose is combined with Deferasirox for making complexes with gadolinium. With replacing the new compound of advanced imaging technology, it transferred from nuclear medicine to Radiology and the results were evaluated in vitro and in vivo that indicated the success in imaging of the heart and cancer in animal tumor model. Conclusion: The mechanism of cancer cells death is through activation of TNF-α system. At present, due to the lack of radiation and radioactive half-life and low production cost and high access to MRI compared with PET, this compound can be considered as 18FDG opponent in the near future as the new MRI successor agent.

A new molecular metallic fragment for labeling biologically active molecules with 99mTc and 188Re is described. This system is composed of a combination of tridentate π-donor and monodentate π-acceptor ligands bound to a [M≡ N]2+ group (M = 99mTc, 188Re) in a pseudo square-pyramidal geometry. A simple structural model of the new metallic fragment was obtained by reacting the ligand 2, 2’-iminodiethanethiol [H2NS2 = NH(CH2CH2SH)2] and monodentate tertiary phosphines with the [M≡N]2+ group (M = 99mTc, 188Re). In the resulting complexes (dubbed3+1complexes), the tridentate ligand binds the [M≡ N]2+ core through the two deprotonated, negatively charged, thiol sulfur atoms and the neutral, protonated, amine nitrogen atom. The residual fourth position of the five-coordinated arrangement is occupied by a phosphine ligand. The chemical identity of these model 99mTc and 188Re compounds was established by comparison with the chromatographic properties of the corresponding complexes obtained at the macroscopic level with the long–lived 99gTc and natural Re isotopes. The investigation was further extended to comprise a series of ligands formed by simple combinations of two basic amino acids or pseudo-amino acids to yield potential tridentate chelating systems having [S, N, S] and [N, N, S] as sets of π-donor atoms. Labeling yields and in vitro stability were investigated using different ancillary ligands. Results showed that SNS-type ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes with both 99mTc and 188Re. Thus, the new chelating system can be conveniently employed for labeling peptides and other biomolecules with the [M≡ N]2+ group.

Objective: The most promising bone pain palliative agent such as 177Lu-EDTMP emerges as a newer radiopharmaceutical for cancer management. Thus, it was of interest to study the cell uptake of this agent in osteocarcinoma cell line and investigate the underlying mechanism of cellular toxicity. Methods: The cell binding studies of 177Lu-EDTMP were carried out in osteocarcinoma cells (MG63) after induction of bone mineralization. Cellular toxicity studies were carried out with varying amounts of 177Lu-EDTMP and compared with equivalent amount of cold Lu-EDTMP. Cell viability was assessed by trypan blue, LDH and MTT assay. Different studies such as DNA fragmentation and Western blotting for apoptosis related proteins were carried out to elucidate the mechanism of cell death. Results: Maximum cell binding of 177Lu-EDTMP, observed with mineralized MG63 cells was 19 ± 0.122 %. Nearly 12% cell death was observed in MG63 cells treated with 37 MBq of 177Lu-EDTMP as compared to controls. Apoptosis studies were carried out by ELISA to estimate DNA fragmentation and it was found that DNA enrichment factor was 1.8, compared to the corresponding control. Down regulation of anti-apoptotic protein, bcl-2 and cleavage of PARP protein was evident by Western blot results. Conclusion: These studies indicate that the 177Lu-EDTMP binds to mineralized bone cells and induces apoptotic cell death in MG63 cells.

Radionuclide therapy (RNT) based on the concept of delivering cytotoxic levels of radiation to disease sites is one of the rapidly growing fields of nuclear medicine. Unlike conventional external beam therapy, RNT targets diseases at the cellular level rather than on a gross anatomical level. This concept is a blend of a tracer moiety that mediates a site specific accumulation followed by induction of cytotoxicity with the short-range biological effectiveness of particulate radiations. Knowledge of the biochemical reactions taking place at cellular levels has stimulated the development of sophisticated molecular carriers, catalyzing a shift towards using more specific targeting radiolabelled agents. There is also improved understanding of factors of importance for choice of appropriate radionuclides based on availability, the types of emissions, linear energy transfer (LET), and physical half-life. This article discusses the applications of radionuclide therapy for treatment of cancer as well as other diseases. The primary objective of this review is to provide an overview on the role of radionuclide therapy in the treatment of different diseases such as polycythaemia, thyroid malignancies, metastatic bone pain, radiation synovectomy, hepatocellular carcinoma (HCC), neuroendocrine tumors (NETs), non-Hodgkin’s lymphoma (NHL) and others. In addition, recent developments on the systematic approach in designing treatment regimens as well as recent progress, challenges and future perspectives are discussed. An examination of the progress of radionuclide therapy indicates that although a rapid stride has been made for treating hematological tumors, the development for treating solid tumors has, so far, been limited. However, the emergence of novel tumor-specific targeting agents coupled with successful characterization of new target structures would be expected to pave the way for future treatment for such tumors.