Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer

Abstract

Human epidermal growth factor receptor 2 (HER2) is a highly expressed tumor marker in epithelial ovarian cancer, and its overexpression is considered to be a potential factor of poor prognosis. Therefore, monitoring the expression of HER2 receptor in tumor tissue provides favorable conditions for accurate localization, diagnosis, targeted therapy, and prognosis evaluation of cancer foci. Affibody has the advantages of high affinity, small molecular weight, and stable biochemical properties. The molecular probes of radionuclide-labeled HER2 affibody have recently shown broad application prospects in the diagnosis and treatment of ovarian cancer; the aim is to introduce radionuclides into the cancer foci, display systemic lesions, and kill tumor cells through the radioactivity of the radionuclides. This process seamlessly integrates the diagnosis and treatment of ovarian cancer. Current research and development of new molecular probes of radionuclide-labeled HER2 affibody should focus on overcoming the deficiencies of non-specific uptake in the kidney, bone marrow, liver, and gastrointestinal tract, and on reducing the background of the image to improve image quality. By modifying the amino acid sequence; changing the hydrophilicity, surface charge, and lipid solubility of the affibody molecule; and using different radionuclides, chelating agents, and labeling conditions to optimize the labeling method of molecular probes, the specific uptake of molecular probes at tumor sites will be improved, while reducing radioactive retention in non-target organs and obtaining the best target/non-target value. These measures will enable the clinical use of radionuclide-labeled HER2 affibody molecular probes as soon as possible, providing a new clinical path for tumor-specific diagnosis, targeted therapy, and efficacy evaluation. The purpose of this review is to describe the application of radionuclide-labeled HER2 affibody in the imaging and treatment of ovarian cancer, including its potential clinical value and dilemmas.

Radiosynthesis, optimization and pharmacokinetic study of the 99mTc-labeled human epidermal growth factor receptor 2 affibody molecule probe 99mTc-(HE)3ZHER2:V2

“…As a commonly used radionuclide for labeling SPECT imaging agents, 99m T has a half-life of 6.02 h, which can be obtained through a 99 Mo- 99m Tc generator and is inexpensive, so it is widely used in clinical and basic research. At present, due to its nonspecific uptake in the liver, gastrointestinal tract, and so on, studies that the molecular probe of 99m Tc-labeled HER2 affibody in ovarian cancer is still in the preclinical research stage [12,18]. Previous study revealed that the hydrophobicity of the HEHEHE tag can reduce the retention of the tracer in the liver [19].…”

“…Currently, commonly used molecular imaging probes targeting HER2 include antibodies, small molecular polypeptides, or proteins that specifically bind to the receptor [2]. Affibody is a kind of scaffold protein with moderate molecular weight, which has the advantages of high affinity with the target molecule, fast clearance in vivo and easy labeling [11,12]. As a radionuclide tracer for SPECT, 99m Tc has a convenient source, low price and good nuclear physics properties, and its labeled molecular probe is suitable for SPECT imaging that is more widely carried out around the world.…”

Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants

“…The reason for this finding may be that their larger size has more mutable sites for binding and better spatial steric resistance after binding. Fortunately, through constructing a dimer/trimer affibody or further mutating other certain residues in the affibody scaffold ( 57 ), the affinity of affibody can be further improved, and the larger size of the dimer or trimer will further improve their spatial steric resistance in the neutralizations. Otherwise, the cocktail therapy mixtures of the affibody with MAbs, or different affibodies together may be another promising strategy.…”

Lesson Learned from a Case of Radioactive Contamination

“…Experimental activities conducted in radioactive environments present varied levels of radiological hazards, depending on the kind and chemical forms of radionuclides (Table ). The chemical analysis of actinides and spent fuel reprocessing frequently involves the use of radionuclides, such as 237 Np, 243/241 Am, and 239/242 Pu, − which are typical α-particle emitters with prolonged half-lives and can pose significant internal exposure risks if ingested. In addition, β-emitting radionuclides, including 90 Sr, 177 Lu, and 131 I, are typically used in therapeutic and theranostic applications. , Moreover, the radioactive decay of these radionuclides often emits γ rays with high penetrating ability .…”