Synthesis of bombesin analogues for radiolabeling with rhenium-188

Safavy, Ahmad; Khazaeli, M. B.; Qin, Haoyu; Buchsbaum, Donald J.

doi:10.1002/(sici)1097-0142(19971215)80:12+<2354::aid-cncr4>3.0.co;2-b

Cited by 44 publications

(109 citation statements)

References 10 publications

(1 reference statement)

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…Cleavage of the peptides from the resin and identification of the CF-labeled peptides was performed as already described above. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY, and [Lys(CF) 4 , Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY. The analytical data of these peptides are summarized in Table I.…”

Section: Labeling With 5(6)-carboxyfluorescein (Cf)mentioning

confidence: 99%

“…21 Several proteolytic enzymes like neutral endopeptidase or metalloendopeptidase have been reported to affect the metabolic stability of peptides in plasma. 22 In the present study, we have studied the metabolic stability of NPY, the Y 2 -receptor selective analog [Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] For modification we chose labelling of the peptides with 5(6)-carboxyfluorescein (CF), in order to discriminate the peptide signal from plasma proteins by HPLC at its excitation/emission wavelengths as 450/517 nm, respectively. In addition to NPY itself the two selective compounds were modified at the N-terminus as well as at the side chain of Lys 4 in order to investigate the best position for modification with respect to metabolic stability.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, we decided not to use any smaller reported analogs, e. g. NPY (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), although this analog has been shown to exhibit some agonistic properties at Y 2 -receptors as well. 36,37 In case of CF-[Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY, which is a centrally truncated Y 2 receptor selective analog, [17][18][19] an enzymatic degradation product CF-[Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17]…”

mentioning

confidence: 99%

“…Structurally, this central truncation was characterized by a helix destabilization because of the lack of a Pro 5 residue, which plays an important role in stabilizing the hairpin-like structure by means of hydrophobic interactions with side chains near the C-terminal segment. Therefore, the C-terminal domain of CF-[Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY is suggested to be more easily accessible for proteolytic enzymes.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Identification of neuropeptide Y cleavage products in human blood to improve metabolic stability

2007

View full text Add to dashboard Cite

Regulatory, receptor‐binding peptides are considered as the agents of choice for diagnostic imaging and therapy of cancers, because their receptors are overexpressed in various human cancer cells. It has been recently indicated that there is a putative role of NPY in breast tumors. The expression of the two best‐investigated NPY receptor subtypes, Y1 and Y2, in breast tissue shows predominant occurrence of the Y1 receptor subtype in tumors, whereas Y2 receptors are found in nonproliferative tissue. To investigate the usefulness of NPY analogs for tumor diagnosis and therapy, we investigated the metabolic stability of receptor‐selective NPY analogs in human blood plasma. NPY analogs were synthesized by Fmoc/t‐Bu solid‐phase strategy. Prior to the cleavage of peptides from the resin, they were labeled with 5(6)‐carboxyfluorescein (CF) either at the N‐terminus or at the side chain of Lys4. For the metabolic stability study, the digestion of peptides was monitored by HPLC and the cleavage products were identified by MALDI‐ToF mass spectrometry. The data showed that full‐length [Phe7, Pro34]NPY analogs, which show high binding affinity to Y1 receptors are enzymatically more stable than centrally truncated analogs, which show high binding affinity to Y2 receptors. Furthermore, the N‐terminally CF‐labeled Y1 and Y2 receptor‐selective peptides were found to be enzymatically more resistant than their counterparts containing the CF label at Lys4 side chain. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 182–189, 2007. This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

show abstract

Section: Labeling With 5(6)-carboxyfluorescein (Cf)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of neuropeptide Y cleavage products in human blood to improve metabolic stability

2007

View full text Add to dashboard Cite

show abstract

“…So far, several bombesin analogues labelled with the diagnostic metallic radionuclides 111 In [39] and 99m Tc have been proposed for the scintigraphic detection of GRP-R-positive lesions [40,41,42,43,44,45,46], while first research efforts toward the development of 111 In- [39] and 188 Re-based radiotherapeutic agents have been reported [47]. Due to the dominance of 99m Tc in nuclear medicine diagnosis, most attempts have been focussed on 99m Tc-based GRP-R-seeking radiotracers involving a wide range of chelators, such as the N 3 S [40,41,42,43], the P 2 S 2 [44] or the carbonyl [45,46] containing frameworks.…”

Section: Introductionmentioning

confidence: 99%

[99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging

Nock

Nikolopoulou

Chiotellis

et al. 2003

Eur J Nucl Med Mol Imaging

172

184

View full text Add to dashboard Cite

Demobesin 1 is a potent new GRP-R-selective bombesin (BN) analogue containing an open chain tetraamine chelator for stable technetium-99m binding. Following a convenient labelling protocol, the radiopeptide, [(99m)Tc]Demobesin 1, formed in nearly quantitative yields and with high specific activities. Both unlabelled and labelled peptide demonstrated high-affinity binding in membrane preparations of the human androgen-independent prostate adenocarcinoma PC-3 cell line. The IC(50) values determined for Demobesin 1 and [Tyr(4)]BN were 0.70+/-0.08 n M and 1.5+/-0.20 n M, respectively, while the K(d) defined for [(99m)Tc/(99g)Tc]Demobesin 1 was 0.67+/-0.10 n M. [(99m)Tc]Demobesin 1 was rather stable in murine plasma, whereas it degraded rapidly in kidney and liver homogenates. After injection in healthy Swiss albino mice, [(99m)Tc]Demobesin 1 accumulated very efficiently in the target organs (pancreas, intestinal tract) via a GRP-R-mediated process, as shown by in vivo receptor blocking experiments. An equally high and GRP-R-mediated uptake was exhibited by [(99m)Tc]Demobesin 1 after injection in PC-3 tumour-bearing athymic mice. The initial high radioligand uptake of 16.2+/-3.1%ID/g in the PC-3 xenografts at 1 h p.i. remained at a similar level (15.61+/-1.19%ID/g) at 4 h p.i. Even after 24 h p.i., when the radioactivity had cleared from all other tissues, a value of 5.24+/-0.67%ID/g was still observed in the tumour. The high and prolonged localization of [(99m)Tc]Demobesin 1 at the tumour site and its rapid background clearance are very promising qualities for GRP-R-targeted tumour imaging in man.

show abstract

in vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215

Płonowski¹,

Nagy²,

Schally³

et al. 2000

Int. J. Cancer

View full text Add to dashboard Cite

The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC‐3 human androgen‐independent prostate cancers. Cytotoxic BN analogue AN‐215, consisting of 2‐pyrrolinodoxorubicin (AN‐201) linked to BN‐like carrier peptide RC‐3094, was injected i.v. at 150 nmol/kg on days 1, 11 and 21. After treatment with AN‐215, tumor volume was 69% (p < 0.01) smaller than that in controls and tumor doubling time was extended from 8.5 ± 0.7 days to 20.3 ± 3.5 days (p < 0.05). Cytotoxic radical AN‐201, carrier RC‐3094 and their unconjugated mixture administered at the same dosage were ineffective. The mortality rate was 12.5% in the AN‐201 group and 16.7% in the group treated with the mixture, but no deaths occurred in mice receiving AN‐215. Because the ester bond linking AN‐201 to the carrier molecule is hydrolyzed much faster in mouse serum than in human serum, in the second experiment we investigated the tolerance to AN‐215 and its effect in nude mice bearing PC‐3 tumors after pharmacological inhibition of serum carboxylesterases. Two applications of AN‐201 at 200 nmol/kg were lethal, whereas no mortality was observed after 4 injections of AN‐215 at the same dose. Administration of 200 nmol/kg AN‐215 on days 1, 7, 17 and 26 again produced 69% tumor inhibition. BN receptors on membranes of PC‐3 tumors were detected by 125I‐[Tyr4]BN binding, and expression of mRNA for BRS‐3 and GRP‐R subtypes was also found. AN‐215 showed a high affinity to PC‐3 tumors, displacing the radioligand at an IC50 of 12.95 ± 0.35 nM. Because BN receptors are present on primary and metastatic prostate cancer, targeted chemotherapy with AN‐215 might benefit patients with advanced prostatic carcinoma who relapsed androgen ablation. Int. J. Cancer 88:652–657, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

Synthesis of bombesin analogues for radiolabeling with rhenium-188

Cited by 44 publications

References 10 publications

Identification of neuropeptide Y cleavage products in human blood to improve metabolic stability

Identification of neuropeptide Y cleavage products in human blood to improve metabolic stability

[99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging

in vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215

Contact Info

Product

Resources

About