Mucin 1 (MUC1) is a large, transmembrane mucin glycoprotein overexpressed in most adenocarcinomas and plays an important role in tumor progression. Regarding its cellular distribution, biochemical features, and function, tumor-related MUC1 varies from the MUC1 expressed in normal cells. Therefore, targeting MUC1 for cancer immunotherapy and imaging can exploit the difference between cancerous and normal cells. Radiopharmaceuticals have a potential use as carriers for the delivery of radionuclides to tumors for a diagnostic imaging and radiotherapy. Several radiolabeled targeting molecules like peptides, antibodies, and aptamers have been efficiently demonstrated in detecting and treating cancer by targeting MUC1. This review provides a brief overview of the current status of developments and applications of MUC1-targeted radiopharmaceuticals in cancer imaging and therapy.

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Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC‐conjugated GnRH analogue and labeled it by 99mTc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys6]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN‐CaP and DU‐145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN‐CaP were superior to DU‐145 cells. The Kd values for LN‐CaP and DU‐145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99mTc‐HYNIC‐Ahx‐[DLys6]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN‐CaP tumor‐xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor‐mediated. The lesion was visualized clearly using 99mTc‐[DLys6]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys6]GnRH peptide as a promising agent for GnRHR‐expressing tumor imaging.

The aim of this study was to prepare radiolabeled peptide‐based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium‐99m, two analogs were designed and compared: an antitumor‐antibody‐derived peptide based on the EPPT sequence and a novel retro‐inverso peptidomimetic derivative D(TPPE) structurally modified by replacing the L‐amino acids with D‐amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC‐conjugated peptides were labeled with 99mTc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99mTc‐HYNIC‐EPPT and 99mTc‐HYNIC‐D(TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99mTc‐HYNIC‐D(TPPE) was more favorable than that of 99mTc‐HYNIC‐EPPT as a result of better tumor‐to‐non‐target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99mTc‐HYNIC‐D(TPPE) in comparison with 99mTc‐HYNIC‐EPPT. The results showed the retro‐inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT‐29 tumors than the parent peptide.

Background: Cancer is the leading cause of death worldwide. Early detection can reduce the disadvantageous effects of diseases and the mortality in cancer. Nuclear medicine is a powerful tool that has the ability to diagnose malignancy without harming normal tissues. In recent years, radiolabeled peptides have been investigated as potent agents for cancer detection. Therefore, it is necessary to modify radiopeptides in order to achieve more effective agents. Objective: This review describes modifications in the structure of radioconjugates with spacers who have improved the specificity and sensitivity of the peptides that are used in oncologic diagnosis and therapy. Methods: To improve the biological activity, researchers have conjugated these peptide analogs to different spacers and bifunctional chelators. Many spacers of different kinds, such as hydrocarbon chain, amino acid sequence, and poly (ethyleneglycol) were introduced in order to modify the pharmacokinetic properties of these biomolecules. Results: Different spacers have been applied to develop radiolabeled peptides as potential tracers in nuclear medicine. Spacers with different charge and hydrophilicity affect the characteristics of peptide conjugate. For example, the complex with uncharged and hydrophobic spacers leads to increased liver uptake, while the composition with positively charged spacers results in high kidney retention. Therefore, the pharmacokinetics of radio complexes correlates to the structure and total charge of the conjugates. Conclusion: Radio imaging technology has been successfully applied to detect a tumor in the earliest stage. For this purpose, the assessment of useful agents to diagnose the lesion is necessary. Developing peptide radiopharmaceuticals using spacers can improve in vitro and in vivo behavior of radiotracers leading to better noninvasive detection and monitoring of tumor growth.