Additionally, the use of the chelator CBTE2A provided improved stability, as uptake of 64Cu-CBTE2A-ReCCMSH was significantly lower than that for 64Cu-DOTA-ReCCMSH in normal organs such as liver, lung, heart, and spleen . and corresponding lung photographs of B16/BL6 Exemestane melanoma-bearing mice at the early stage (a, b) and late stage (c, d) of tumor development. (I) 18F-5-FPN PET images of two mice with lung metastases from melanoma. Note that this probe was able to detect both micrometastases (a, b) and wide spread lung metastases (c, d) from melanoma. Tumors are indicated by red arrows. Adapted and modified with permission from references [45C47, 49, 51, 52, 66, 67]. 2.2. Imaging of melanoma metastases Considering that the presence of distant metastases, especially brain metastases, confers worse prognosis for patients with melanoma, their early detection is critical . In a study comparing diagnostic values of 18F-FDG PET/CT and MRI in melanoma patients with palpable lymph node metastases, Aukema et al. found that 18F-FDG PET/CT changed the intended regional node dissection in 26 patients (37%) and resulted in a superior diagnostic accuracy of 93%, but missed 5 patients with brain metastases which were detected by MRI . Other study also demonstrated that 18F-FDG PET failed to detect metastatic lesions of less than 1 cm located in the lung, liver or brain . Currently only contrast-enhanced MRI and 18F-FET PET seem to be reliable methods to detect brain metastases from melanoma but still lack specificity [10, 59]. Moreover, in patients with surgically treatable IIIC and IV metastatic melanoma following targeted/immunotherapy, PET/CT can detect unexpected metastases that are missed with conventional imaging, and can be considered as part of preoperative workup [4, 60, 61]. Thus it is of great importance to develop novel radiotracers to identify occult lesions or distant small metastases from melanoma with high specificity and a low false positive rate. Notably, the ability of an imaging agent to cross the bloodCbrain barrier (BBB) is considered critical to effectively target metastatic lesions in the brain. Of the reported probes, 4-11C-MBZA was able to cross the BBB and the corresponding uptake was moderate in the normal brain . As observed from biodistribution and PET studies, 4-11C-MBZA uptake in normal tissues was noticeably lower than that for several other 18F-benzamides like 18F-FPBZA  and 18F-DAFBA . In addition, newly developed radiotracers, such as 18F-FBZA, 18F-5-FPN,18F-MEL050, 18F-FITM and 18F-ICF01006 (Fig. 2H), may have better performance in the delineation of small lymph node and lung metastases from melanoma than that of 18F-FDG PET/CT [45, 46, 63C66]. 18F-5-FPN, a probe identical to 18F-2, successfully detected pigmented B16/F10 tumors as early as 1 min after injection of the tracer. The uptake increased over time and the tracer was rapidly excreted via the kidneys. This and later studies from the same group further validated the potential of 18F-5-FPN PET for the early detection of metastatic melanoma lesions (Fig. 2I) [63, 67]. 18F-MEL050 Exemestane had excellent retention in melanin-containing tumors and rapid background clearance ; however it is notable that the route of administration of 18F-MEL050 matters when imaging regional lymph node metastasis from melanoma. While 18F-MEL050 PET correctly identified 100% of the lymph node metastases after subcutaneous administration of the tracer, only 60% of those metastases were found after systemic administration of the tracer in the lateral tail vein . 3. Peptide-based imaging probes Peptides are emerging as potent and selective ligands that can be designed to bind with high affinity and specificity to cell surface receptors on a wide range of tumors . Three major types INK4B of peptides, namely -Melanocyte-stimulating hormone (-MSH), tumor angiogenesis associated integrins, and peptides targeting both MC1R and integrin, are under intensive development for molecular imaging of melanoma. 3.1. -Melanocyte-stimulating Exemestane hormone (-MSH)-based probes -MSH, a ligand specific for melanocortin receptor subtype 1 (MC1R), has been reported to be overexpressed in both melanotic and amelanotic human melanoma cases and has been widely used as a.