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J Nucl Med. 2011 Dec;52 Suppl 2:42S-55S. doi: 10.2967/jnumed.110.085753.

Radiopeptide imaging and therapy in Europe.

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  • 1Nuclear Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy.


Receptor targeting with radiolabeled peptides has become an important topic, particularly in nuclear oncology. Strong research efforts are under way in radiopharmaceutical science laboratories and in nuclear medicine departments in Europe. The target receptors belong to the large family of G-protein-coupled receptors. The prototypes of these radiopeptides are based on analogs of somatostatin targeting somatostatin receptor-positive tumors, particularly well-differentiated neuroendocrine tumors. These radiopeptides have an important impact not only on diagnosis but also on targeted radionuclide therapy of these tumors. Besides the registered radiopeptide (111)In-pentetreotide, efficient SPECT tracers labeled with (99m)Tc and PET agents based on generator-produced (68)Ga have been developed and used in the clinic. In parallel to the development of diagnostic agents, radiopeptides labeled with the β(-) emitters (90)Y and (177)Lu are also widely used. Because the same chelators and therefore the same conjugates can be used in diagnosis and therapy, they constitute ideal theranostic pairs. This progress is driven not only by scientists and clinicians but also by patient interest groups. New radiopeptides targeting other G-protein-coupled receptors are entering the clinic, among them glucagon-like peptide 1 receptor-targeting molecules. This receptor is overexpressed on literally all benign insulinomas. (111)In-labeled derivatives of the insulinotropic 39-mer peptide exendin-4 were beneficial in the pre- and perioperative localization of these benign lesions. In contrast, lack of localization may indicate malignant insulinoma. The bombesin- and gastrin-releasing peptide receptor family is potentially important because these receptors are overexpressed on major human tumors such as prostate tumors, breast tumors, gastrointestinal stromal tumors, and vessels of ovarian cancer. (99m)Tc-labeled peptides for SPECT and (68)Ga-, as well as (64)Cu-labeled agonists or antagonists, have been studied in breast tumors, prostate tumors, gastrointestinal stromal tumors, and gliomas with considerable success. A phase I therapeutic study with a (177)Lu-labeled agonist has been completed. There are not enough clinical data available to reveal the significance of these new modalities in patient care, but several phase I studies are under way in larger patient cohorts using PET agents. Another G-protein-coupled receptor with high overexpression on human tumors is the gastrin/cholecystokinin-2 receptor. It is overexpressed in more than 90% of cases of medullary thyroid cancer, in small cell lung cancer, and in a subgroup of neuroendocrine tumors. Correlating with in vitro receptor localization using autoradiography of 27 patients with metastasized medullary thyroid cancer, SPECT or planar imaging of these patients resulted in a 95% sensitivity of tumor localization. Finally, another G-protein-coupled receptor is found in brain tumors and peritumoral vessels. Literally all cases of glioblastoma multiforme overexpress the neurokinin type 1 receptor; the natural ligand is substance P, which was metabolically stabilized, labeled with (90)Y and (213)Bi, and injected into resection cavities or directly into tumors, which were critically located via a catheter system. The major advantage of this approach appeared to be the facilitated resectability of tumors, particularly in those patients who had been treated up front with the locoregional approach. It appears that neoadjuvant treatment before resection is a valid concept. Finally, another peptide family, the arginine-glycine-aspartate-based radiotracers, has made it to the clinic labeled with a variety of radioisotopes for monitoring the integrins α(v)β(3) overexpressed during tumor angiogenesis.

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