Tumor localization of a radiolabeled bombesin analogue in mice bearing human ovarian tumors induced to express the gastrin-releasing peptide receptor by an adenoviral vector

Rogers, Buck E.; Curiel, David T.; Mayo, Matthew S.; Laffoon, Kim K.; Bright, Sheila J.; Buchsbaum, Donald J.

doi:10.1002/(sici)1097-0142(19971215)80:12+<2419::aid-cncr13>3.0.co;2-f

Cited by 18 publications

(9 citation statements)

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“…In this regard, various BN analogues have been radiolabeled with radioactive iodine or radioactive metals. In particular, 131 I, 149 Pm, 188 Re, and 177 Lu have been used to radiolabel BN analogues for potential radiotherapy applications through their beta emissions ( − ), while 99m Tc- and 111 In-labeled analogues have been used for detecting GRPR-positive tumors by gamma ray scintigraphy ( − ). Positron-emission tomography (PET) should have better resolution than gamma camera imaging at the sensitivity needed for imaging GRPR expression; therefore, a BN analogue radiolabeled with a positron-emitter would have advantages over a gamma ray emitting radioisotope for detecting GRPR-positive tumors.…”

Section: Introductionmentioning

confidence: 99%

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a ⁶⁴Cu-Labeled Bombesin Analogue

et al. 2003

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The gastrin-releasing peptide receptor (GRPR) is overexpressed on a variety of carcinomas and has been the target for detection and treatment of these neoplasms in animals. In particular, analogues of the tetradecapeptide bombesin (BN) have been radiolabeled with (99m)Tc and (111)In for detection of GRPR-positive tumors by gamma ray scintigraphy. The goal of this study was to evaluate the potential of the bombesin analogue, DOTA-Aoc-BN(7-14), for positron-emission tomographic (PET) imaging after radiolabeling with the positron-emitter (64)Cu. A saturation binding assay on PC-3 human prostate cancer cells showed that (64)Cu-DOTA-Aoc-BN(7-14) had an equilibrium binding constant (K(d)) of 6.1 +/- 2.5 nM and a receptor concentration (B(max)) of 2.7 +/- 0.6 x 10(5) receptors/cell. The radiolabeled analogue also showed rapid internalization with 18.2% internalized into 10(5) PC-3 cells by 2 h. The tumor localization of (64)Cu-DOTA-Aoc-BN(7-14) was 5.5% injected dose per gram in athymic nude mice bearing PC-3 xenografts at 2 h postinjection. The tumor retention with respect to the 2 h value was 76% and 45% at 4 and 24 h, respectively, and was GRPR-mediated as shown by inhibition with a coinjection of excess peptide. MicroPET imaging of (64)Cu-DOTA-Aoc-BN(7-14) in athymic nude mice bearing subcutaneous PC-3 tumors showed good tumor localization. Further studies with (64)Cu-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) ((64)Cu-PTSM) suggested that low blood flow to the PC-3 tumors may have limited the localization of (64)Cu-DOTA-Aoc-BN(7-14). This study demonstrates that (64)Cu-DOTA-Aoc-BN(7-14) can be used to detect GRPR-positive tumors by PET imaging.

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Section: Introductionmentioning

confidence: 99%

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a ⁶⁴Cu-Labeled Bombesin Analogue

et al. 2003

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“…The various BBN analogues studied range from structures in which the radiolabeled moiety is conjugated to the nearly full-length BBN (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) sequence, to where it is attached to a smaller truncated amino acid sequence comprising the GRPreceptor binding moiety (e.g., BBN [8][9][10][11][12][13][14]NH 2 ). Results of studies to evaluate these conjugates demonstrate that radiolabeled BBN/GRP analogues hold important promise as cancer specific radiopharmaceuticals (26)(27)(28)(29)(30)(31)(32)(33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

“…The synthesis and characterization of radiolabeled BBN or GRP analogues has been reported by several groups ( − ). Several of these analogues, labeled with radioiodine and radiometals, have been shown to bind selectively and avidly to GRP receptors on cancer cells, both in vitro and in vivo ( − ).…”

Section: Introductionmentioning

confidence: 99%

“…The synthesis and characterization of radiolabeled BBN or GRP analogues has been reported by several groups (26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Several of these analogues, labeled with radioiodine and radiometals, have been shown to bind selectively and avidly to GRP receptors on cancer cells, both in vitro and in vivo (26)(27)(28)(29)(30)(31)(32)(33)(34)(35). The various BBN analogues studied range from structures in which the radiolabeled moiety is conjugated to the nearly full-length BBN (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) sequence, to where it is attached to a smaller truncated amino acid sequence comprising the GRPreceptor binding moiety (e.g., BBN [8][9][10][11][12][13][14]NH 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Radiochemical Investigations of ^99mTc−N₃S-X-BBN[7−14]NH₂: An in Vitro/in Vivo Structure−Activity Relationship Study Where X = 0-, 3-, 5-, 8-, and 11-Carbon Tethering Moieties

et al. 2002

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Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and specificity. The GRPr is overexpressed on a variety of human cancer cells, including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to develop (99m)Tc-radiolabeled BBN analogues that maintain high specificity for the GRPr in vivo. A preselected synthetic sequence via solid-phase peptide synthesis (SPPS) was designed to produce N(3)S-BBN (N(3)S = dimethylglycyl-l-seryl-l-cysteinylglycinamide) conjugates with the following general structure: DMG-S-C-G-X-Q-W-A-V-G-H-L-M-(NH(2)), where the spacer group, X = 0 (no spacer), omega-NH(2)(CH(2))(2)COOH, omega-NH(2)(CH(2))(4)COOH, omega-NH(2)(CH(2))(7)COOH, or omega-NH(2)-(CH(2))(10)COOH. The new BBN constructs were purified by reversed phase-HPLC (RP-HPLC). Electrospray mass spectrometry (ES-MS) was used to characterize the nonmetalated BBN conjugates. Re(V)-BBN conjugates were prepared by the reaction of Re(V)gluconate with N(3)S-X-BBN[7-14]NH(2) (X = 0 carbons, beta-Ala (beta-alanine), 5-Ava (5-aminovaleric acid), 8-Aoc (8-aminooctanoic acid), and 11-Aun (11-aminoundecanoic acid)) with gentle heating. Re-N(3)S-5-Ava-BBN[7-14]NH(2) was also prepared by the reaction of [Re(V)dimethylglycyl-l-seryl-l-cysteinylglycinamide] with 5-Ava-BBN[7-14]NH(2). ES-MS was used to determine the molecular constitution of the new Re(V) conjugates. The (99m)Tc conjugates were prepared at the tracer level by each the prelabeling, post-conjugation and pre-conjugation, postlabeling approaches from the reaction of Na[(99m)TcO(4)] with excess SnCl(2), sodium gluconate, and corresponding ligand. The (99m)Tc and Re(V) conjugates behaved similarly under identical RP-HPLC conditions. In vitro and in vivo models demonstrated biological integrity of the new conjugates.

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“…Different modified forms of octreotide can be labelled with radioisotopes of halogens or metals for the purposes of imaging [23] or therapy [24,25]. Rogers et al [26] recently employed recombinant adenoviral vectors to induce somatostatin receptors on human non-small cell lung cancer cells and on human ovarian carcinoma cells in vitro. This resulted in specific binding of radiolabelled octreotide.…”

Section: Receptor Gene Expression To Facilitate Peptide Targetingmentioning

confidence: 99%

Applications of Gene Transfer to Targeted Radiotherapy

Mairs

Cunningham²,

Boyd³

et al. 2000

CPD

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For targeted radionuclide therapy to succeed as a single modality treatment, schemes must be devised which will enable the deposition in malignant cells of sterilising doses of radiation. Until such methods have been perfected, it is necessary to combine targeted radiotherapy in a rational manner with conventional anti-cancer treatments. Several means of delivery of therapeutic radionuclides are being evaluated but none of these yet appears to be as powerful as the simplest and most effective example, viz: sodium [131I]iodide treatment of disseminated thyroid carcinoma. The radiopharmaceutical [131I]meta-iodobenzylguanidine ([131I]MIBG) is an effective single agent for the treatment of neuroblastoma. However, uptake of the drug in malignant sites is heterogeneous, suggesting that this therapy alone is unlikely to cure disease. A growing body of experimental evidence indicates exciting possibilities for the integration of gene transfer with radionuclide targeting. This review covers aspects of the combination of gene manipulation and targeted radiotherapy, emphasising the potential of gene transfer to facilitate tumour targeting with low molecular weight radiopharmaceuticals.

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Tumor localization of a radiolabeled bombesin analogue in mice bearing human ovarian tumors induced to express the gastrin-releasing peptide receptor by an adenoviral vector

Cited by 18 publications

References 8 publications

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a ⁶⁴Cu-Labeled Bombesin Analogue

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a ⁶⁴Cu-Labeled Bombesin Analogue

Radiochemical Investigations of ^99mTc−N₃S-X-BBN[7−14]NH₂: An in Vitro/in Vivo Structure−Activity Relationship Study Where X = 0-, 3-, 5-, 8-, and 11-Carbon Tethering Moieties

Applications of Gene Transfer to Targeted Radiotherapy

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Tumor localization of a radiolabeled bombesin analogue in mice bearing human ovarian tumors induced to express the gastrin-releasing peptide receptor by an adenoviral vector

Cited by 18 publications

References 8 publications

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a 64Cu-Labeled Bombesin Analogue

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a 64Cu-Labeled Bombesin Analogue

Radiochemical Investigations of 99mTc−N3S-X-BBN[7−14]NH2: An in Vitro/in Vivo Structure−Activity Relationship Study Where X = 0-, 3-, 5-, 8-, and 11-Carbon Tethering Moieties

Applications of Gene Transfer to Targeted Radiotherapy

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MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a ⁶⁴Cu-Labeled Bombesin Analogue

MicroPET Imaging of a Gastrin-Releasing Peptide Receptor-Positive Tumor in a Mouse Model of Human Prostate Cancer Using a ⁶⁴Cu-Labeled Bombesin Analogue

Radiochemical Investigations of ^99mTc−N₃S-X-BBN[7−14]NH₂: An in Vitro/in Vivo Structure−Activity Relationship Study Where X = 0-, 3-, 5-, 8-, and 11-Carbon Tethering Moieties