antagonist radioligands ͉ tumor targeting ͉ peptide hormones ͉ neuropeptides ͉ receptor internalization P eptide receptor targeting in vivo is a successful method to image and treat various types of cancers (1). The best example is somatostatin receptor targeting with 111 In-, 90 Y-, or 177 Lu-labeled somatostatin radioligands that are injected into the patients intravenously and accumulate in their somatostatin receptor-expressing tumors. For this purpose, agonists have been selected. The rationale is that agonists, after high-affinity binding to the receptor, usually trigger internalization of the ligandreceptor complex (2). This process of internalization is the basis for an efficient accumulation of the radioligand in a cell over time (1,(3)(4)(5), and it has been considered a crucial step in the process of in vivo receptor targeting with radiolabeled peptides (4-6). Recently, a highly significant correlation between the rate of ligand internalization in vitro into AR42J cells expressing somatostatin receptor subtype 2 (sst 2 ) and the in vivo uptake in the sst 2 -expressing rat tumor model has been reported

RM2 was shown to be a potent GRPr antagonist. Pharmacokinetics and imaging studies indicate that (111)In-RM2 and (68)Ga-RM2 are ideal candidates for clinical SPECT and PET studies.

Purpose Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available β-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using 111 In-labelled derivatives. Methods Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All 111 In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to 111 In-DTPA-minigastrin 0 (0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Conclusions Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in lower metabolic stability. The properties of the macrocyclic chelator-bearing derivatives make them potentially suitable for clinical purposes.

There is yet no consensus on the application of functional imaging and qualitative image interpretation in the management of gastric cancer. In this second part, we will discuss the role of image-derived quantitative parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/ CT) in gastric cancer, as both techniques have been shown to be promising and useful tools in the clinical decision making of this disease. We will focus on different aspects including aggressiveness assessment, staging and Lauren type discrimination, prognosis prediction and response evaluation. Although both the number of articles and the patients enrolled in the studies were rather small, there is evidence that quantitative parameters from DCE-MRI such as K trans , V e , K ep and AUC could be promising image-derived surrogate parameters for the management of gastric cancer. Data from 18 F-FDG PET/CT studies showed that standardised uptake value (SUV) is significantly associated with the aggressiveness, treatment response and prognosis of this disease. Along with the results from diffusion-weighted MRI and contrast-enhanced multidetector computed tomography presented in Part 1 of this critical review, there are additional image-derived quantitative parameters from DCE-MRI and 18 F-FDG PET/CT that hold promise as effective tools in the diagnostic pathway of gastric cancer. Key Points • Quantitative analysis from DCE-MRI and 18 F-FDG PET/CT allows the extrapolation of multiple image-derived parameters. • Data from DCE-MRI (K trans , V e , K ep and AUC) and 18 F-FDG PET/CT (SUV) are non-invasive, quantitative image-derived parameters that hold promise in the evaluation of the aggressiveness, treatment response and prognosis of gastric cancer.

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