Technetium‐99m labeled epidermal growth factor‐tumor imaging in mice

Abstract

We have shown previously that the epidermal growth factor peptide (EGF) may be radiolabeled with 99mTc at room temperature and neutral pH by using the N‐hydroxysuccinimide ester of S‐acetyl mercaptoacetyltriglycine (MAG3) as a bifunctional chelator. By a competition binding assay, we found that MAG3‐conjugated EGF retained biological activity. Furthermore, the labeled peptide exhibited saturation binding to EGF receptor‐positive tumor cell lines which could be inhibited by presaturation of the cells with unlabeled, native EGF. Biodistribution in normal mice at 3 h postadministration showed rapid clearance with minimal retention of the label in sampled organs. We have now investigated the tumor localization properties in mice of this labeled peptide. Nude mice implanted with the EGF receptor‐positive tumors A431 and LS‐174T were administered labeled EGF and a labeled control peptide (BPTI, aprotinin). Tumor uptake at 12 h postadministration was 0.44% injected dose/g for EGF/g vs. 0.09 for the control. Pretreatment of tumored mice with unlabeled EGF blocked about half the tumor uptake. Animals were also administered an anti‐EGF receptor antibody labeled with 99mTc via MAG3. Relative to the antibody, tumor‐to‐muscle ratios were improved from 6 to 15 and tumor‐to‐blood ratios from 0.4 to 7 with EGF. These favorable results along with documented evidence of overexpression of the EGF receptor in many human tumors suggest that 99mTc‐EGF should be considered further for tumor detection. © Munksgaard 1997.

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

“…On the other hand, the ligand EGF and an irreversible inhibitor of EGFR have been evaluated. However, using 111 In-DTPA-EGF or 99m Tc-EGF, no discrimination could be made between high and moderate EGFR overexpression [54,55], and the synthetic molecule ML04 displayed only minor EGFR-specific uptake [56].…”

Radioimmunoscintigraphy of pancreatic cancer in tumor-bearing athymic nude mice using 99mtechnetium-labeled anti-KL-6/MUC1 antibody

“…Labeling of monoclonal antibodies with 99m Tc has been found to be effective for radioimmunoscintigraphy. [8][9][10][11]14 The antibody was labeled with 99m Tc as described by Karube et al 8 with minor modifi cations. Anti-KL-6/ MUC1 antibody (2.5 mg) was reduced by reaction with 2-mercaptoethanol at room temperature for 60 min.…”

“…[3][4][5] Specifi c monoclonal antibodies are extremely powerful tools for the diagnosis or treatment of some diseases; for example, daclizumab (a monoclonal antibody against the α chain of the interleukin 2 receptor) has been used to prevent acute rejection after renal transplantation 6 and rituximab (a monoclonal antibody against CD20) has been used to treat lymphomas. 7 Radiolabeling of tumorspecifi c antibodies for use as in vivo tracers has been attempted to detect the distribution of neoplasms by scintigraphy, [8][9][10][11] and one of these approaches is now in clinical use. 12 Mucins comprise a group of high-molecular-weight glycoproteins.…”

A Narrative Review of 99mTc-Aprotinin in the Diagnosis of Cardiac Amyloidosis and a New Life for an Unfairly Abandoned Drug

“…There are other reports regarding the specificity of Tc-labeled aprotinin, the lack of significant binding to EGFr tumours in a mouse model, and the low non-specific uptake in an experimental rat model of sterile or Staphylococcus-induced inflammation [ 10 , 11 ].…”