Metalloprobes for functional monitoring of tumour multidrug resistance by nuclear imaging

Abstract

Cancer chemotherapy has been used since the early 1950s and still remains one the major therapeutic options for many malignant tumours. A major obstacle to successful cancer chemotherapy is drug resistance. Frequently resistance is intrinsic to the cancer, but as therapy becomes more effective, acquired resistance has also become more frequent. One form of resistance, named multidrug resistance (MDR), is responsible for the failure of tumours to respond to a wide spectrum of chemotherapeutic agents. The in vivo monitoring of MDR could assist in the selection of patients for therapy and can avoid ineffective and potentially toxic treatments. Therefore, methods for functionally interrogating MDR transport activity have been sought, namely single photon emission computed tomography (SPECT) and positron emission tomography (PET). Cationic radiotracers originally developed as SPECT myocardial imaging agents, such as [(99m)Tc(MIBI)(6)](+) and [(99m)Tc(tetrofosmin)(2)O(2)](+), are used for both early cancer detection and non-invasive monitoring of the tumour MDR transport function. With the ultimate goal of obtaining better performing radioprobes for MDR imaging, other metal-based complexes and/or small molecules have also been synthesized and biologically evaluated. In this perspective we will report on the chemical efforts made to find metalloprobes for in vivo monitoring of MDR by nuclear imaging techniques. The current knowledge on the biological mechanisms and proteins involved in tumour MDR will be also briefly presented, as its understanding is invaluable for the rational design and biological evaluation of new radioprobes.

Perfusion and Specific Radioprobes for Cardiac Imaging

“…It is well know that cancer cells and tumours also maintain a more negative potential owing to increased metabolic requirements, and as a result, there is an increased accumulation of 99m Tcsestamibi, 99m Tc-tetrofosmin and 99m Tc-TMEOP in malignant tumours. This feature permits the use of these radiotracers for imaging cancers of the breast, lung, brain and parathyroid adenomas (reviewed in Mendes et al, 2011).…”

Radiosynthesis and Biological Evaluation of 68Ga-Labeled Colchicine Conjugates

“…Functional molecular imaging of MDR using single-photon emission computed tomography and positron emission tomography (PET) can help to identify multidrug-resistant tumors and thus decide alternative therapeutic regimens for patients who are resistant to drugs used in the chemotherapeutic modality. 9,10 Radiolabeled colchicine can be a suitable molecular probe for imaging of Pgp transport activity in vivo and thus help in early diagnosis of MDR. The potential of colchicine for tumor imaging and assessing antiangiogenic effect has been very well documented in the use of 99m Tc-ethylenedicysteine colchicine ( 99m Tc-EC Colchicine).…”

Biogenic Silver Nanoparticles Decorated with Methylene Blue Potentiated the Photodynamic Inactivation of Pseudomonas aeruginosa and Staphylococcus aureus

“…The emergence of several new diseases and multidrug resistant (MDR) bacterial strains has accelerated the drug discovery program for the search of novel drugs. Advancements in science and technology have facilitated the development of early diagnosis, better prevention, and advanced treatment options to control the disease [1]. Antibiotics are known as one of the major therapeutic agents employed in the treatment of infectious diseases.…”