A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation

Kuo Shyan Lin, Andrew Luu, Kwamena E. Baidoo, Hossein Hashemzadeh-Gargari, Ming Kai Chen, Kenneth Brenneman, Roberto Pili, Martin Pomper, Michael A. Carducci, Henry N. Wagner

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

99mTc-labeled bombesin analogues have shown promise for noninvasive detection of many tumors that express bombesin (BN)/gastrin- releasing peptide (GRP) receptors. 99mTc-labeled peptides, however, have a tendency to accumulate in the liver and intestines due to hepatobiliary clearance as a result of the lipophilicity of the 99mTc chelates. This makes the imaging of lesions in the abdominal area difficult. In this study, we have synthesized a new high affinity 99mTc-labeled BN analogue, [DTPA1, Lys3(99mTc-Pm-DADT), Tyr 4]BN, having a built-in pharmacokinetic modifier, DTPA, and labeled with 99mTc using a hydrophilic diaminedithiol chelator (Pm-DADT) to effect low hepatobiliary clearance. In vitro binding studies using human prostate cancer PC-3 cell membranes showed that the inhibition constant (K i) for [DTPA1, Lys3(99Tc-Pm-DADT), Tyr4]BN was 4.1 ± 1.4 nM. Biodistribution studies of [DTPA1, Lys3(99mTc-Pm-DADT), Tyr4]BN in normal mice showed very low accumulation of radioactivity in the liver and intestines (1.32 ± 0.13 and 4.58 ± 0.50% ID, 4 h postinjection, respectively). There was significant uptake (7.71 ± 1.37% ID/g, 1 h postinjection) in the pancreas which expresses BN/GRP receptors. The uptake in the pancreas could be blocked by BN, partially blocked by neuromedin B, but not affected by somatostatin, indicating that the in vivo binding was BN/GRP receptor specific. Scintigraphic images showed specific, high contrast delineation of prostate cancer PC-3 xenografts in SCID mice. Thus, the new peptide has a great potential for imaging BN/GRP receptor-positive cancers located even in the abdomen.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalBioconjugate Chemistry
Volume16
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Technetium
Bombesin
Peptides
Bombesin Receptors
Liver
Imaging techniques
Intestines
Pharmacokinetics
Pancreas
Prostatic Neoplasms
Radioactivity
Cell membranes
Tumors
Pentetic Acid
SCID Mice
Chelating Agents
Somatostatin
Heterografts
Abdomen
Gastrins

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Lin, K. S., Luu, A., Baidoo, K. E., Hashemzadeh-Gargari, H., Chen, M. K., Brenneman, K., ... Wagner, H. N. (2005). A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation. Bioconjugate Chemistry, 16(1), 43-50. https://doi.org/10.1021/bc049820h

A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation. / Lin, Kuo Shyan; Luu, Andrew; Baidoo, Kwamena E.; Hashemzadeh-Gargari, Hossein; Chen, Ming Kai; Brenneman, Kenneth; Pili, Roberto; Pomper, Martin; Carducci, Michael A.; Wagner, Henry N.

In: Bioconjugate Chemistry, Vol. 16, No. 1, 01.2005, p. 43-50.

Research output: Contribution to journalArticle

Lin, KS, Luu, A, Baidoo, KE, Hashemzadeh-Gargari, H, Chen, MK, Brenneman, K, Pili, R, Pomper, M, Carducci, MA & Wagner, HN 2005, 'A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation', Bioconjugate Chemistry, vol. 16, no. 1, pp. 43-50. https://doi.org/10.1021/bc049820h
Lin KS, Luu A, Baidoo KE, Hashemzadeh-Gargari H, Chen MK, Brenneman K et al. A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation. Bioconjugate Chemistry. 2005 Jan;16(1):43-50. https://doi.org/10.1021/bc049820h
Lin, Kuo Shyan ; Luu, Andrew ; Baidoo, Kwamena E. ; Hashemzadeh-Gargari, Hossein ; Chen, Ming Kai ; Brenneman, Kenneth ; Pili, Roberto ; Pomper, Martin ; Carducci, Michael A. ; Wagner, Henry N. / A new high affinity technetium-99m-bombesin analogue with low abdominal accumulation. In: Bioconjugate Chemistry. 2005 ; Vol. 16, No. 1. pp. 43-50.
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abstract = "99mTc-labeled bombesin analogues have shown promise for noninvasive detection of many tumors that express bombesin (BN)/gastrin- releasing peptide (GRP) receptors. 99mTc-labeled peptides, however, have a tendency to accumulate in the liver and intestines due to hepatobiliary clearance as a result of the lipophilicity of the 99mTc chelates. This makes the imaging of lesions in the abdominal area difficult. In this study, we have synthesized a new high affinity 99mTc-labeled BN analogue, [DTPA1, Lys3(99mTc-Pm-DADT), Tyr 4]BN, having a built-in pharmacokinetic modifier, DTPA, and labeled with 99mTc using a hydrophilic diaminedithiol chelator (Pm-DADT) to effect low hepatobiliary clearance. In vitro binding studies using human prostate cancer PC-3 cell membranes showed that the inhibition constant (K i) for [DTPA1, Lys3(99Tc-Pm-DADT), Tyr4]BN was 4.1 ± 1.4 nM. Biodistribution studies of [DTPA1, Lys3(99mTc-Pm-DADT), Tyr4]BN in normal mice showed very low accumulation of radioactivity in the liver and intestines (1.32 ± 0.13 and 4.58 ± 0.50{\%} ID, 4 h postinjection, respectively). There was significant uptake (7.71 ± 1.37{\%} ID/g, 1 h postinjection) in the pancreas which expresses BN/GRP receptors. The uptake in the pancreas could be blocked by BN, partially blocked by neuromedin B, but not affected by somatostatin, indicating that the in vivo binding was BN/GRP receptor specific. Scintigraphic images showed specific, high contrast delineation of prostate cancer PC-3 xenografts in SCID mice. Thus, the new peptide has a great potential for imaging BN/GRP receptor-positive cancers located even in the abdomen.",
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AU - Chen, Ming Kai

AU - Brenneman, Kenneth

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AB - 99mTc-labeled bombesin analogues have shown promise for noninvasive detection of many tumors that express bombesin (BN)/gastrin- releasing peptide (GRP) receptors. 99mTc-labeled peptides, however, have a tendency to accumulate in the liver and intestines due to hepatobiliary clearance as a result of the lipophilicity of the 99mTc chelates. This makes the imaging of lesions in the abdominal area difficult. In this study, we have synthesized a new high affinity 99mTc-labeled BN analogue, [DTPA1, Lys3(99mTc-Pm-DADT), Tyr 4]BN, having a built-in pharmacokinetic modifier, DTPA, and labeled with 99mTc using a hydrophilic diaminedithiol chelator (Pm-DADT) to effect low hepatobiliary clearance. In vitro binding studies using human prostate cancer PC-3 cell membranes showed that the inhibition constant (K i) for [DTPA1, Lys3(99Tc-Pm-DADT), Tyr4]BN was 4.1 ± 1.4 nM. Biodistribution studies of [DTPA1, Lys3(99mTc-Pm-DADT), Tyr4]BN in normal mice showed very low accumulation of radioactivity in the liver and intestines (1.32 ± 0.13 and 4.58 ± 0.50% ID, 4 h postinjection, respectively). There was significant uptake (7.71 ± 1.37% ID/g, 1 h postinjection) in the pancreas which expresses BN/GRP receptors. The uptake in the pancreas could be blocked by BN, partially blocked by neuromedin B, but not affected by somatostatin, indicating that the in vivo binding was BN/GRP receptor specific. Scintigraphic images showed specific, high contrast delineation of prostate cancer PC-3 xenografts in SCID mice. Thus, the new peptide has a great potential for imaging BN/GRP receptor-positive cancers located even in the abdomen.

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