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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD

Created: ; Last Update: March 4, 2010.

Chemical name:N-(2-(Diethylamino)ethyl)-5-[123I]iodonicotinamideimage 85756801 in the ncbi pubchem database
Abbreviated name:[123I]MEL008, [123]1
Agent category:Compound
Target category:Receptor
Method of detection:single photon emission computed tomography (SPECT)
Source of signal:123I
  • Checkbox In vitro
  • Checkbox Rodents
Click on the above structure for additional information in PubChem.



Malignant melanoma is the sixth most common cancer in the United States (1). Early diagnosis and prompt surgical removal comprise the best approach for a possible cure because malignant melanoma is a very aggressive cancer (2). Melanomas develop from activated or genetically altered neoplastic melanocytes that contain melanin (3-5). Melanin pigment is synthesized and deposited within melanosomes (6). Eumelanin and pheomelanin are the two major types of melanin. Eumelanin is the predominant melanin pigment found in primary tumors. Pheomelanin tends to associate with progression of the disease. Melanins are complex, negatively charged molecules with hydrophobic surfaces, and they have the capability to bind many different types of compounds (3). Therefore, melanins represent a very attractive target for both diagnosis and treatment.

Benzamide (BZA) derivatives and iodobenzamides have been found to have affinity for melanomas (3, 7-9). The exact mechanisms of uptake of these compounds have not been fully established (7, 10, 11). Direct melanin binding, involvement in the melanin biosynthesis pathway, and sigma (σ) receptor mediation have been proposed as the most likely mechanisms for different compounds. In addition, available vascular concentrations of these compounds and their ability to transport into the melanoma cells also influence their cellular uptake (11). Melanin-targeting radiopharmaceuticals that are based on BZA such as [123I]BZA, [123I]BZA2, and [123I]IBZM have been investigated and developed for molecular imaging of malignant melanomas (12-14). To produce a radioiodinated probe with higher tumor uptake and faster body clearance, Liu et al. (15) designed and prepared N-(2-(diethylamino)ethyl)-5-[123I]iodonicotinamide ([123I] MEL008), which has an alkylpiperazinyl moiety. Their study showed that [123I]MEL008 has a high selective uptake in the murine B16F0 melanoma tumor, and the uptake was most likely related to melanin binding and not to σ receptor binding.



Liu et al. (15) reported the synthesis of [123I]MEL008 by the standard peracetic acid oxidative radioiodination of the 5-trimethylstannyl derivative. [123I]MEL008 was purified with HPLC with a radiochemical purity of >95% and a specific activity of >2 GBq/nmol (54 mCi/nmol) at EOS. Lipophilicity of [123I]MEL008 was 1.55 (log P7.5) as determined by HPLC.

In Vitro Studies: Testing in Cells and Tissues


In vitro competitive binding assays of unlabeled MEL008 to σ1 and σ2 receptors in guinea pig brain membranes were conducted with 2 nM [3H](+)-pentazocine and 100 nM [3H]1,3-di-o-tolylguanidine, respectively. Very low affinities for both receptors were found. MEL008 exhibited Ki values of 3,100 and >50,000 nM for σ1 and σ2 receptors, respectively.

Animal Studies



Liu et al. (15) performed biodistribution studies in black mice (n = 5/group) bearing murine melanotic B-16F0 or nude mice bearing A375 human amelanotic melanoma tumors after injection of 0.37-0.74 MBq (10-20 μCi) [123I]MEL008. In the B16F0 tumor model, there was high tumor radioactivity uptake, low normal organ radioactivity uptake, and rapid body clearance. The tumor radioactivity levels in percentage injected dose per gram (% ID/g) were 7.8 ± 1.7 (1 h), 6.0 ± 0.4 (3 h), 5.9 ± 0.7 (6 h), 3.2 ± 0.9 (24 h), and 2.2 ± 0.4 (48 h). At 1 h, the radioactivity levels (% ID/g) in other major organs were 2.0 ± 0.4 (liver), 1.8 ± 0.3 (kidney), 1.4 ± 0.2 (lung), 0.8 ± 0.1 (heart), 0.14 ± 0.02 (brain), and 1.2 ± 0.2 (blood). At 24 h, these levels (% ID/g) decreased to 0.12 (liver), 0.03 (kidney), 0.04 (lung), 0.15 (heart), 0.01 (brain), and 0.03 (blood). The tumor/mouse mean contrast ratios (MCR) were 4 (1 h), 7 (3 h), 12 (6 h), 37 (24 h), and 22 (48 h). The thyroid activity uptakes (% ID) were minimal, ranging from 0.37 ± 0.07 at 1 h to 1.4 ± 0.3 at 48 h. In comparison, a similar normal organ distribution pattern was observed in the A375 amelanotic melanoma, but the tumor radioactivity levels (n = 5) were very low with 0.40 ± 0.16% ID/g (1 h), 0.13 ± 0.06% ID/g (6 h), and 0.00I% D/g (24 h). The MCR values were 14 (1 h), 2 (6 h), and 0.04 (24 h). A blocking study was performed in the B16F0 mice with 1 mg/kg haloperidol (σ1 and σ2 inhibitor) administered 5 min before the [123I]MEL008 injection. At 1 h and 24 h, no inhibition was observed in the tumor, liver, kidney, and lung. Metabolic studies were performed by injecting 3–5 MBq (0.081–0.135 mCi) [123I]MEL008 into mice bearing B16F0 tumors. Plasma, brain, and tumor samples were obtained at 0.25, 1, and 24 h after injection. Thin-layer chromatography analysis indicated that 70-80% of the plasma radioactivity represented polar radioactive metabolites at 0.25-24 h. At these time points, 70-90% of the radioactivity in the brain and tumor represented intact [123I]MEL008. Gamma planar imaging was performed in mice bearing B16F0 melanotic tumors or A375 amelanotic melanomas. A dose of 10 MBq (0.27 mCi) [123I]MEL008 was administered by i.v. injection, and images were obtained 0.5 and 24 h after injection. The results showed that mice bearing B16F0 tumors and urinary bladder had the highest tumor radioactivity levels at 24 h. The eyes and thyroid were visualized with lower radioactivity levels. In comparison, only the urinary bladder and thyroid were visualized in the A375 tumor mice.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.


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