Abstract
The aim of this study was to synthesis an imaging agent for tumor targeting. New recombinant insulin analogue was successfully produced from E. coli by recombinant DNA technique, and was well labeled with Technetium-99m with a high radiochemical yield of 93.3 ± 2.1 %. Moreover, it showed good in-vitro stability in both saline and human serum. Preclinical evaluation of Technetium-99m [99mTc] Tc-insulin in solid tumor-bearing mice showed high accumulation in tumor tissues. The T/NT (target to non-target ratio) was of 5.4, after 60 min. of post injection (p.i). The direct intra-tumoral (I.T) injection of [99mTc] Tc-insulin showed good retention in tumor tissues with a ratio more than 50 % after 15 min. As a result of the promising bio-distribution studies; the newly recombinant insulin showed good uptake in tumor site, which assured high concentration of insulin receptor on tumor cell surface, accompanied with high cell density of tumor cells as well. This work affords a potential radio-carrier that could be used as a good tumor marker and imaging probe via SPECT (Single Photon Emission Computed Tomography) technique, after further preclinical studies.
Highlights
Cancer is the main cause of mortality, and the number of diseased patients with cancer is increasing at an alarming rate
De novo strategy has been developed for producing recombinant human insulin protein (6.92 kDa) in E. coli, via direct assembly of full-length gene contacting chain A and B connected by only five residues of amino acids
The radiochemical yield was low at pH below or above the optimum pH of the reaction medium. This was attributed to the formation of reduced hydrolyzed Technetium (RH-99mTc) colloid, which was the main radiochemical impurity in reference to Essa et al, (2015)
Summary
Cancer is the main cause of mortality, and the number of diseased patients with cancer is increasing at an alarming rate. Nuclear medicine technique was one of the most popular techniques used for cancer detection (Ibrahim et al, 2014; Sakr et al, 2014). Technetium-99m is the most radionuclides which emit gamma rays used in nuclear medicine; due to its perfect characteristics (6.02 h physical half-life and 140 keV γ-ray energy), Abdelaziz et al, 2019 low cost and good availability (Dilworth and Parrott, 1998; Sakr et al, 2012; Motaleb et al, 2018b). Insulin receptor isoform A (IR-A) expression has been detected in cancer cells of the breast; lung, colon (Frasca et al.; 1999), ovaries (Kalli et al, 2002), thyroid gland (Vella et al, 2002), smooth and striated muscles (Sciacca et al, 2002)
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