(A) Imaging of the expression of carcinoembryonic antigen (CEA) with radiolabeled antibody fragments in mice. evaluation of fresh targeted drugs. Examples include imaging of the manifestation and inhibition of drug focuses on, noninvasive cells pharmacokinetics, and early assessment of the tumor response. analyzed 47 individuals with recurrent breast cancer.11 At the time of diagnosis, all main tumors were estrogen receptor positive; however, only 23% of the individuals achieved an objective response to salvage hormonal therapy. However, the degree of binding of the radiolabeled estrogen analog [18F]fluoroestradiol (FES) to estrogen receptors in metastatic tumors, as measured by PET, was predictive of the tumor response. Specifically, none of the individuals lacking focal FES tumor binding responded to therapy, whereas 34% of individuals with FES tumor binding responded to salvage hormonal therapy. Therefore, FESCPET can be used to determine patient subgroups that, despite manifestation of estrogen receptors in the primary tumor, are unlikely to benefit from antiestrogen therapy because the metastatic tumors are estrogen receptor bad. In addition to identifying variations in manifestation of target proteins among individuals, molecular imaging can also display intrapatient heterogeneity of the manifestation of target proteins. For instance, lesion-to-lesion variations in the manifestation of V3 integrin in a patient with metastatic smooth cells sarcoma are demonstrated in Number 1. The designated variations in V3 integrin manifestation found in this patient shown the potential of molecular imaging for prediction and might clarify the heterogeneous reactions to different MK-0773 targeted medicines within a single individual.12 Currently, the levels of manifestation of target proteins are determined by analysis of tumor biopsies. In individuals with metastatic disease, analysis of tumor biopsies allows evaluation of only a small part of the total tumor mass. Number 1 illustrates the assessment of the manifestation of protein MK-0773 focuses on by use of biopsies might, therefore, become misleading, since V3 integrin was highly expressed in the primary tumor but not in the pulmonary metastases. Open in a separate window Number 1 Intrapatient heterogeneity in the manifestation of V3 integrin imaged by PET with the V3 ligand [18F]galacto-RGD. The primary tumor, a smooth tissue sarcoma of the thigh (arrow in the CT image inside a), demonstrates intense uptake of [18F]galacto-RGD, indicating high manifestation levels of V3 integrin (arrow in B). Uptake of [18F]galacto-RGD is much less pronounced inside a bone metastasis in the pelvis and a right-sided lung metastasis (arrows in D). The bottom image in C shows the pelvic metastasis on CT (arrows). A left-sided lung metastasis, demonstrated on CT (C, top) is bad within the [18F] galacto-RGD PET scan (D). Permission from the Society of Nuclear Medicine ? Ale AJ (2005) Biodistribution and pharmacokinetics of the V3-selective tracer 18F-galacto-RGD in MK-0773 malignancy individuals. 46: 1333C1341. Abbreviations: RGD, arginineCglycineCaspartic acid; SUV, standardized uptake value. Currently, only a limited quantity of molecular focuses on can be imaged in medical studies because of the restricted quantity of available probes (Table 1).13C17 Most molecular focuses on are expressed at nanomolar concentrations in the tumor cells, which presents challenging for the development of ligands. Many potential probes not only bind with high affinity to their focuses on but also demonstrate considerable nonspecific binding and/or unfavorable pharmacokinetic properties for imaging. Reducing nonspecific binding and optimizing the pharmacokinetic properties have been major difficulties in the development of fresh imaging probes. Table 1 Examples of molecular imaging probes for studying UNG2 the manifestation of therapeutic focuses on in individuals. (1988)13Androgen receptors[18F]FDHTLarson (2004)14Somatostatin receptors[68Ga]octreotide analogsHofmann (2001)15[18F]octreotide analogsSchottelius (2004)16V3 integrins[18F]RGD-peptidesHaubner (2005)17 Open in a separate windows Abbreviations: FDHT,16-[18F]fluoro-5-dihydrotestosterone; FES, [18F]fluoro-17-estradiol; RGD, arginineCglycineCaspartic acid. Several fresh strategies for the development of a variety of molecular imaging probes have been tested successfully in animals. Radiolabeled antibodies have been used to image a variety of focuses on, but their sluggish clearance from your bloodstream and cells results in limited image contrast. Recent improvements in antibody executive18,19 have led to the development of several antibody fragment types that demonstrate superb properties for targeted PET imaging in animals.