Assessment of epidermal growth factor receptor with 99mTc–ethylenedicysteine–C225 monoclonal antibody

Abstract

Epidermal growth factor receptor (EGFR) plays an important role in cell division and cancer progression, as well as angiogenesis and metastasis. Since many tumor cells exhibit the EGFR on their surface, functional imaging of EGFR provides not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-EGFR therapy could be assessed effectively. C225 is a chimeric monoclonal antibody that targets the human extracellular EGFR and inhibits the growth of EGFR-expressing tumor cells. Also, it has been demonstrated that C225, in combination with chemotherapeutic drugs or radiotherapy, is effective in eradicating well-established tumors in nude mice. We have developed 99mTc-labeled C225 using ethylenedicysteine (EC) as a chelator. This study aimed at measuring uptake of 99mTc-EC-C225 in EGFR+ tumor-bearing animal models and preliminary feasibility of imaging patients with head and neck carcinomas. In vitro Western blot analysis and cytotoxicity assays were used to examine the integrity of EC-C225. Tissue distribution studies of 99mTc-EC-C225 were evaluated in tumor-bearing rodents at 0.5-4 h. In vivo biodistribution of 99mTc-EC-C225 in tumor-bearing rodents showed increased tumor-to-tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC-C225 to assess EGFR expression. SPECT images confirmed that the tumors could be visualized with 99mTc-EC-C225 from 0.5 to 4 h in tumor bearing rodents. We conclude that 99mTc-EC-C225 may be useful to assess tumor EGFR expression. This may be useful in the future for selecting patients for treatment with C225.

Assessment of Therapeutic Tumor Response Using 99mTc-Ethylenedicysteine-Glucosamine

“…Compared to 18 F-FDG autoradiogram, less brain and heart uptake was observed in 99m Tc-EC-DG by visualization. Tumor uptake was well visualized by 99m Tc-EC-DG (Fig.…”

“…Though FDG-PET imaging demonstrates the increased glucose consumption of malignant cells, problems with specificity for cell proliferation have led to the development of new PET tracers. 18 F-FDG could assess metabolic activity, but it could not adequately assess cell nuclei activity. Thus, 18 F-FDG imaging could not differentiate infection/inflammation from tumor recurrence.…”

“…18 F-FDG could assess metabolic activity, but it could not adequately assess cell nuclei activity. Thus, 18 F-FDG imaging could not differentiate infection/inflammation from tumor recurrence. Serial imagings have been proposed to measure a greater retention of FDG in tumors, but they are practically limited with a 2-hour half-life of 18 F. To develop a tumorspecific agent, it is necessary to assess cell nuclei activity.…”

“…11,12 We have previously reported a series of 99m Tc-EC-agent conjugates for functional imaging in oncology. [13][14][15][16][17][18][19][20] In addition, EC can also be labeled with 68 Ga for PET imaging and 188 Re (a beta and gamma emitter) for internal radionuclide therapy. 21-23 99m Tc, 68 Ga, and 188 Re are generator-produced isotopes that are accessible and affordable.…”

“…Briefly, 99m Tc-EC-DG (100 Ci) was incubated in dog serum (200 l) at 37°C at 0. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] hours. The serum samples were diluted with 50% methanol in water, and radio-TLC was used to analyze the product.…”