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                                Chapter 5
Introduction
The gastrin releasing peptide receptor (GRPR) is a G-protein coupled receptor overexpressed in a number of cancer types such as prostate cancer, breast cancer and gastrointestinal cancer, thereby representing an attractive molecule for tumor targeting [1, 2]. Multiple GRPR radioligands have been synthesized during the past decade, mainly for the purpose of receptor-mediated nuclear imaging and therapy [3, 4]. These studies, at the preclinical as well as clinical level, have expanded our knowledge on GRPR radioligands and have proven that targeting of GRPR for nuclear imaging and/or therapy can be beneficial in patient care [5-8]. Moreover, research has demonstrated that GRPR antagonists are usually superior to agonists for tumor targeting, in addition to exhibiting less adverse events [9, 10].
Sarabesin 3 (SB3) is a recently developed GRPR antagonist that has excellent receptor affinity and good in vivo stability when labeled with the positron- emitting radionuclide gallium-68 (68Ga; t1/2: 68 minutes). Preclinical as well as clinical PET imaging studies using [68Ga]SB3 have been performed with great success [11, 12]. A novel and interesting approach would be the use of SB3 for pre-operative imaging and intra-operative radio-guided tumor detection of GRPR-expressing tumors, especially for the detection of GRPR-expressing metastases and non-palpable tumors.
Radio-guided tumor detection is based on the intra-operative localization of malignant lesions using handheld detection probes following injection of a radiopharmaceutical (Fig. 1). Combining this intra-operative method with information from pre-operative nuclear imaging by single photon emission computed tomography (SPECT) or positron emission tomography (PET), together with computed tomography (CT) or magnetic resonance imaging (MRI), allows for accurate surgical guidance, ultimately improving surgical outcome while minimizing surgical invasiveness [13].
Currently, radio-guided surgery is successfully applied clinically for lymphoscintigraphy in melanoma and breast cancer patients, radio-guided occult lesion localization and radio-guided seed localization of non-palpable tumors, as well as minimal invasive parathyroid surgery for removal of
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