Radiopeptide Imaging and Therapy in the United States

Radiolabeled peptides targeted against receptors on the cell surface have been shown to be remarkably specific and effective in the diagnosis and therapy of malignant disease. Much of the early work in this field took place outside the United States, but in recent years the research effort within the United States has accelerated. Most of the initial studies in the United States focused on somatostatin receptor ligands. 111In-pente-treotide was approved in 1994 and has been used extensively in the diagnosis and management of a wide variety of neuroendo-crine tumors, particularly carcinoid. This work was extended to 99mTc-labeled analogs, and the most successful, 99mTc-dep-reotide, was approved in 1999. This agent was found to be accurate in the diagnosis of lung cancer, but it was not partic-ularly successful because it was supplanted by 18F-FDG imag-ing with positron tomography. More recently, studies with 68Ga-labeled somatostatin analogs were initiated in the United States. This effort was delayed relative to that in other parts of the world because of difficulty in obtaining the necessary gen-erators and regulatory uncertainty, both of which are less of a problem currently. Several ligands are being developed to image melanoma through targeting of the melanocyte-stimulat-ing hormone receptor. Other ligands are being developed to use the arginine-glycine-aspartate oligopeptide to target angiogen-esis and to use bombesin analogs to target the gastrin-releas-ing peptide receptor for the diagnosis and potential therapy of prostate cancer. Peptide dimers that target 2 receptors simul-taneously are also being constructed, potentially increasing the selectivity of the approach significantly. Radiopeptide therapy has been explored with these ligands, initially with high-dose 111In-pentetreotide. This step has been followed by U.S. partic-ipation in several trials with 90Y-, 177Lu-, and 188Re-labeled ana-logs. Some of these agents are now available clinically outside the United States, and it is important to design and conduct the appropriate trials so that this therapy can be offered within th