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| Chemical name: | 99mTc-(Hydrazinonicotinic acid-β-Ala-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2)(tricine)(TPPTS) | |
| Abbreviated name: | 99mTc-HYNIC-ABN, 99mTc-(HYNIC-ABN)(tricine)(TPPTS) | |
| Synonym: | ||
| Agent category: | Peptide | |
| Target: | Gastrin-releasing peptide receptor (GRPR) | |
| Target category: | Receptor | |
| Method of detection: | SPECT, gamma planar imaging | |
| Source of signal\contrast: | 99mTc | |
| Activation: | No | |
| Studies: |
| Click on protein, nucleotide (RefSeq), and gene for more information about gastrin-releasing peptide receptor. |
[PubMed]
The amphibian bombesin (BBN or BN, a peptide of 14 amino acids), is an analog of human gastrin-releasing peptide (GRP, a peptide of 27 amino acids) that binds to GRP receptors (GRPR) with high affinity and specificity (1, 2). Both GRP and BBN share an amidated C-terminus sequence homology of 7 amino acids, -Trp-Ala-Val-Gly-His-Leu-Met-NH2. BBN-Like peptides have been shown to induce various biological responses in diverse tissues, including the central nervous system (CNS) and the gastrointestinal (GI) system. They also act as potential growth factors for both normal and neoplastic tissues (3). Specific BBN receptors (BBN-R) have been identified on CNS and GI tissues and a number of tumor cell lines (4). The BBN-R superfamily includes at least 4 different subtypes, namely neuromedin B (NMB or BB1), the GRPR subtype (BB2), BB3, and BB4. The findings of GRPR overexpression in various human tumors, such as breast, prostate, lung, colon, ovarian, and pancreatic cancers, provide opportunities for tumor imaging by designing specific molecular imaging agents to target the GRPR (5, 6).
Shi et al. (7) have used a ternary ligand system (HYNIC, tricine and TPPTS) for labeling β-Ala-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 (ABN). HYNIC (hydrazinonicotinic acid) is a bifunctional coupling agent for 99mTc-labeling, while tricine and TPPTS (trisodium triphenylphosphine-3,3',3''-trisulfonate) were used as coligands to prepare the ternary ligand complex [99mTc(HYNIC-ABN)(tricine)(TPPTS)] for SPECT imaging GRPR of colon cancer.
[PubMed]
A solution (0.32 ml) of tricine (10 mg), SnCl2 (0.06 mg), 370 MBq (10 mCi) Na99mTcO4 and HYNIC-ABN (0.01 mg) was incubated at room temperature for 10 min (7). A solution (0.1 ml) of TPPTS (6 mg) was added in the reaction mixture and heated at 100°C for 30 min. 99mTc(HYNIC-ABN)(tricine)(TPPTS) was purified with Sep-Pak. The specific activity of the purified product was 44.4 GBq/mmol (1.2 Ci/mmol) with a radiochemical purity of >95%. The logP value was -2.39. 99mTc(HYNIC-ABN)(tricine)(TPPTS) was >95% intact after 12 h in saline and in the presence of 1 mg/ml of cysteine.
[PubMed]
Shi et al. (7) performed in vitro inhibition studies of ABN and HYNIC-ABN in cultured PC-3 human prostate cancer cells with 125I-[Tyr4]BBN. The IC50 values were 24 ± 2 nM and 38 ± 1 nM, respectively. In vitro internalization and efflux studies of 99mTc(HYNIC-ABN)(tricine)(TPPTS) were performed in cultured HT-29 human colon cancer cells at 37ºC. HT-29 cells exhibited a rapid internalization with 35% of radioactivity at 5 min after incubation and reached a maximal cellular radioactivity of 68% at 30 min. However, only ~20% of the internalized radioactivity remained after 1 h of incubation in tracer-free medium.
[PubMed]
Shi et al. (7) performed biodistribution studies of 99mTc(HYNIC-ABN)(tricine)(TPPTS) in nude mice bearing HT-29 xenografts. Tumor uptake values were 1.59% ID/g at 30 min, 1.2% ID/g at 60 min, and 0.8% ID/g at 120 min. The organ with the highest uptake was the kidney (~9% ID/g) with little radioactivity in the muscle (0.14% ID/g), blood (0.50% ID/g), intestine (0.63% ID/g), lung (0.60% ID/g) and liver (0.68% ID/g) at 60 min after injection. Tumor/blood, tumor/liver, and tumor/muscle ratios were 2.37, 1.69, and 11.17, respectively. Most of the injected radioactivity was found in the urine sample at 60 min after injection. No intact 99mTc(HYNIC-ABN)(tricine)(TPPTS) was detected in the urine, kidney, and liver samples at 60 min after injection. SPECT imaging in nude mice bearing HT-29 xenografts was performed with 14.8 MBq (0.4 mCi) of 99mTc(HYNIC-ABN)(tricine)(TPPTS). The tumors, kidneys and urinary bladder were clearly visualized at 1 h after injection. Pre-administration of excess HYNIC-ABN substantially inhibited the radioactivity in the tumors, liver, stomach, intestine and kidneys.
R01 CA115883
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