High resolution MicroPET technology has recently been developed. 64Cu-DOTA-PEG-E[c(RGDyK)]2 (64Cu-RGD) is a cyclic RGD peptide that has previously demonstrated specific binding to ávâ3-integrin; a cell-cell adhesion molecule implicated in angiogenesis and metastasis, and expressed in many tumors including NSCLC. We studied the feasibility of serial MicroPET imaging in an orthotopic murine model of human lung cancer utilizing 18FDG and 64Cu-RGD.
Human lung adenocarcinoma cells (NCI-H1975) were implanted in the left lung upper lobe, and subcutaneously to the right flank of 6 week-old SCID-bg mice (2x106cells). MicroPET images were acquired (Concorde Microsystems, Knoxville, TN) after injection of 18FDG (1,2,3,4 weeks) and 64Cu-RGD (4 weeks). Relative tracer uptake was expressed as the ratio of mean counts in tumor to reference regions. Autoradiography or necroscopy was performed at four weeks.
Tumor growth and progression to mediastinal metastases were detectable using 18FDG in all mice, but mediastinal disease was masked by intense cardiac uptake. 64Cu-DOTA-RGD demonstrated specific uptake in tumor deposits with an uptake value of 7.5 as compared with 2.6 for 18FDG (Figure).
Serial imaging of growth and progression of lung cancer in small animals is possible using MicroPET. Marker specific imaging with 64Cu-RGD provides an improved in vivo tool to study tumor biology.
In the future, marker peptides may be coupled to chemotherapeutic or radiotherapeutic compounds, allowing cell specific delivery and dynamic imaging of therapeutic response in cancer patients.
E.M. Sievers, None.