On their plasma membranes, cells express receptor
proteins with high affinity for regulatory
peptides, such as
somatostatin. Changes in the density of these receptors during disease, for example, overexpression in many
tumors, provide the basis for new imaging methods. The first
peptide analogues successfully applied for visualization of receptor-positive
tumors were radiolabeled
somatostatin analogues. The next step was to label these analogues with therapeutic
radionuclides for
peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicenter studies already have shown an effective therapeutic response when using radiolabeled
somatostatin analogues to treat receptor-positive
tumors. Infusion of positively charged
amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of
CCK-B receptor-positive
tumors, such as medullary
thyroid carcinoma, radiolabeled
minigastrin analogues currently are being successfully applied. The combination of different
therapy modalities holds interest as a means of improving the clinical
therapeutic effects of radiolabeled
peptides. The combination of different
radionuclides, such as (177)Lu- and (90)Y-labeled
somatostatin analogues, to reach a wider
tumor region of high curability, has been described. A variety of other
peptide-based radioligands, such as
bombesin and NPY(Y(1)) analogues, receptors for which are expressed on common
cancers such as prostate and
breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multireceptor
tumor targeting using the combination of
bombesin and NPY(Y(1)) analogues is promising for scintigraphy and PRRT of
breast carcinomas and their
lymph node metastases.