Human trial of F-18 galacto-RGD measures avb3 expression of metastatic disease


CONTEXT: The integrin avb3 affects angiogenesis and tumor cell metastasis and is the target of several promising cancer therapies. Roland Haubner, Ph.D., and colleagues at the University of Munich developed F-18 galacto-RGD for noninvasive monitoring of avb3 with PET. After successfully quantifying avb3 expression with the agent in microPET mouse studies, they show that the probe can measure avb3 expression in humans with metastatic disease.

RESULTS: Nine patients with metastatic melanoma, soft-tissue sarcoma, metastatic renal cell carcinoma, or villonodular synovitis were scanned with whole-body PET in three separate acquisitions performed seven, 10.5, and 79 minutes after a 185-MBq injection of F-18 galacto-RGD. Attenuation-corrected images and mean standard uptake values normalized to patient body weight were acquired. Fast clearance and low tracer uptake in organs other than the kidneys, spleen, liver, and intestine were observed. Tumor accumulation varied greatly, with SUVs ranging from 1.2 to 10.

The agent's washout characteristics were similar to those of F-18 FDG, producing comparable radiation exposure, but their tumor uptake patterns were quite different. Multiple lesions characterized from high FDG uptake in two melanoma patients were apparent in only one case with galacto-RGD. These differences underscore the importance of determining avb3 expression before starting therapy, according to Haubner. A correlation between F-18 galacto-RGD uptake and receptor density was established using immunohistochemistry and Western blot tests. As with other PET probes, tumor uptake is influenced by perfusion, vascular permeability, and necrosis. Trial results were published online (PLoS Medicine 2005;2[3]:e70).

IMAGE: A soft-tissue sarcoma in the dorsal region of a right knee was characterized with intense F-18 galacto-RGD uptake on a PET image that was fused with a contrast-enhanced CT image that hyperenhanced the same region. Immunohistochemistry of the peripheral tumor (right) confirms the presence of angiogenic processes.

IMPLICATIONS: The study established the feasibility of F-18 RGD-PET for studying avb3 expression during angiogenesis. It has potential in drug trials for assessing performance of avb3 antagonists and may play a clinical role for monitoring anti-angiogenic cancer therapies and characterizing angiogenic processes associated with inflammation.

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