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Pretargeted immuno-PET of CEA-expressing intraperitoneal human colonic tumor xenografts: a new sensitive detection method.

Schoffelen R, van der Graaf WT, Sharkey RM, Franssen GM, McBride WJ, Chang CH, Laverman P, Goldenberg DM, Oyen WJ, Boerman OC - EJNMMI Res (2012)

Bottom Line: One hour after the radiolabeled peptide or FDG was given, micro-PET/computed tomography images were acquired.Thereafter, the uptake of the 68Ga or 18F in dissected tissue was determined.Pretargeted immuno-PET with bsmAb and a 68Ga-labeled peptide could be a very sensitive imaging method for imaging colonic cancer, disclosing occult lesions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept, of Nuclear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, 9101, The Netherlands. r.schoffelen@nucmed.umcn.nl.

ABSTRACT

Background: In this study, pretargeted immuno-positron-emission tomography [PET] with a bispecific monoclonal anti-carcinoembryonic antigen [CEA] (CEACAM5) × anti-hapten antibody (bispecific monoclonal antibody [bsmAb]) and a small (1.5 kD) peptide labeled with 68Ga was compared to fludeoxyglucose [18F-FDG]-PET for detecting intraperitoneal [i.p.] CEA-expressing human colonic tumor xenografts in nude mice.

Methods: Two groups of female BALB/c nude mice were inoculated with LS174T human colonic tumor cells i.p. One group received 5 MBq 18F-FDG, and the other received intravenous injections of the bsmAb, followed 16 h later with 5 MBq of 68Ga-labeled peptide. One hour after the radiolabeled peptide or FDG was given, micro-PET/computed tomography images were acquired. Thereafter, the uptake of the 68Ga or 18F in dissected tissue was determined.

Results: Within 1 h, high uptake of the 68Ga-labeled peptide in the tumor lesions (23.4 ± 7.2% ID/g) and low background activity levels were observed (e.g., tumor-to-intestine ratio, 58 ± 22). This resulted in a clear visualization of all intra-abdominal tumor lesions ≥ 10 μL and even some tumors as small as 5 μL (2 mm diameter). 18F-FDG efficiently localized in the tumors (8.7 ± 3.1% ID/g) but also showed physiological uptake in various normal tissues (e.g., tumor-to-intestine ratio, 3.9 ± 1.1).

Conclusions: Pretargeted immuno-PET with bsmAb and a 68Ga-labeled peptide could be a very sensitive imaging method for imaging colonic cancer, disclosing occult lesions.

No MeSH data available.


Related in: MedlinePlus

Images. 3D-volume rendering of the pretargeted immuno-PET scan (a) and the FDG-PET/CT scan (b) of the BALB/c nude mice with intraperitoneal LS174T tumors that received 6.0 nmol TF2 and 5 MBq 68Ga-IMP288 (0.25 nmol) with a 16-h interval (a) or 18F-FDG (b). The animals were imaged 1 h after 68Ga-IMP288 or 18F-FDG injection. Digital pictures were made during dissection to localize and measure individual tumors. On the pretargeted immuno-PET/CT images (a), all dissected tumors were very clearly distinguishable, except for the two very small tumors (1.2 and 4.7 μL, respectively). In the FDG-PET/CT images (b), arrows are pointed at the localizations where tumors were found at dissection, but the signal was difficult to be discriminated from the intestines. Figure 3c, d shows the PET/CT images of mice without intraperitoneal images after TF2 and 68Ga-IMP288 injection (c) or 18F-FDG injection (d).
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Figure 3: Images. 3D-volume rendering of the pretargeted immuno-PET scan (a) and the FDG-PET/CT scan (b) of the BALB/c nude mice with intraperitoneal LS174T tumors that received 6.0 nmol TF2 and 5 MBq 68Ga-IMP288 (0.25 nmol) with a 16-h interval (a) or 18F-FDG (b). The animals were imaged 1 h after 68Ga-IMP288 or 18F-FDG injection. Digital pictures were made during dissection to localize and measure individual tumors. On the pretargeted immuno-PET/CT images (a), all dissected tumors were very clearly distinguishable, except for the two very small tumors (1.2 and 4.7 μL, respectively). In the FDG-PET/CT images (b), arrows are pointed at the localizations where tumors were found at dissection, but the signal was difficult to be discriminated from the intestines. Figure 3c, d shows the PET/CT images of mice without intraperitoneal images after TF2 and 68Ga-IMP288 injection (c) or 18F-FDG injection (d).

Mentions: Immuno-PET with TF2 and 68Ga-IMP288 resulted in a clear delineation of the tumors. An example of a PET/CT image is shown in Figure 3a. It shows the cross sections through several tumor lesions. The photographs show their localization in the abdomen as well as their size. Apart from the activity in the bladder, very low uptake in normal tissues was seen. Due to the highly specific uptake in the tumor lesions and low background concentration, the immuno-PET/CT images could even be used to guide the localization of tumor lesions during dissection. Tumors that were more difficult to find macroscopically because they were localized in the retroperitoneal cavities or posterior to the liver were easily seen and localized on the images.


Pretargeted immuno-PET of CEA-expressing intraperitoneal human colonic tumor xenografts: a new sensitive detection method.

Schoffelen R, van der Graaf WT, Sharkey RM, Franssen GM, McBride WJ, Chang CH, Laverman P, Goldenberg DM, Oyen WJ, Boerman OC - EJNMMI Res (2012)

Images. 3D-volume rendering of the pretargeted immuno-PET scan (a) and the FDG-PET/CT scan (b) of the BALB/c nude mice with intraperitoneal LS174T tumors that received 6.0 nmol TF2 and 5 MBq 68Ga-IMP288 (0.25 nmol) with a 16-h interval (a) or 18F-FDG (b). The animals were imaged 1 h after 68Ga-IMP288 or 18F-FDG injection. Digital pictures were made during dissection to localize and measure individual tumors. On the pretargeted immuno-PET/CT images (a), all dissected tumors were very clearly distinguishable, except for the two very small tumors (1.2 and 4.7 μL, respectively). In the FDG-PET/CT images (b), arrows are pointed at the localizations where tumors were found at dissection, but the signal was difficult to be discriminated from the intestines. Figure 3c, d shows the PET/CT images of mice without intraperitoneal images after TF2 and 68Ga-IMP288 injection (c) or 18F-FDG injection (d).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298693&req=5

Figure 3: Images. 3D-volume rendering of the pretargeted immuno-PET scan (a) and the FDG-PET/CT scan (b) of the BALB/c nude mice with intraperitoneal LS174T tumors that received 6.0 nmol TF2 and 5 MBq 68Ga-IMP288 (0.25 nmol) with a 16-h interval (a) or 18F-FDG (b). The animals were imaged 1 h after 68Ga-IMP288 or 18F-FDG injection. Digital pictures were made during dissection to localize and measure individual tumors. On the pretargeted immuno-PET/CT images (a), all dissected tumors were very clearly distinguishable, except for the two very small tumors (1.2 and 4.7 μL, respectively). In the FDG-PET/CT images (b), arrows are pointed at the localizations where tumors were found at dissection, but the signal was difficult to be discriminated from the intestines. Figure 3c, d shows the PET/CT images of mice without intraperitoneal images after TF2 and 68Ga-IMP288 injection (c) or 18F-FDG injection (d).
Mentions: Immuno-PET with TF2 and 68Ga-IMP288 resulted in a clear delineation of the tumors. An example of a PET/CT image is shown in Figure 3a. It shows the cross sections through several tumor lesions. The photographs show their localization in the abdomen as well as their size. Apart from the activity in the bladder, very low uptake in normal tissues was seen. Due to the highly specific uptake in the tumor lesions and low background concentration, the immuno-PET/CT images could even be used to guide the localization of tumor lesions during dissection. Tumors that were more difficult to find macroscopically because they were localized in the retroperitoneal cavities or posterior to the liver were easily seen and localized on the images.

Bottom Line: One hour after the radiolabeled peptide or FDG was given, micro-PET/computed tomography images were acquired.Thereafter, the uptake of the 68Ga or 18F in dissected tissue was determined.Pretargeted immuno-PET with bsmAb and a 68Ga-labeled peptide could be a very sensitive imaging method for imaging colonic cancer, disclosing occult lesions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept, of Nuclear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, 9101, The Netherlands. r.schoffelen@nucmed.umcn.nl.

ABSTRACT

Background: In this study, pretargeted immuno-positron-emission tomography [PET] with a bispecific monoclonal anti-carcinoembryonic antigen [CEA] (CEACAM5) × anti-hapten antibody (bispecific monoclonal antibody [bsmAb]) and a small (1.5 kD) peptide labeled with 68Ga was compared to fludeoxyglucose [18F-FDG]-PET for detecting intraperitoneal [i.p.] CEA-expressing human colonic tumor xenografts in nude mice.

Methods: Two groups of female BALB/c nude mice were inoculated with LS174T human colonic tumor cells i.p. One group received 5 MBq 18F-FDG, and the other received intravenous injections of the bsmAb, followed 16 h later with 5 MBq of 68Ga-labeled peptide. One hour after the radiolabeled peptide or FDG was given, micro-PET/computed tomography images were acquired. Thereafter, the uptake of the 68Ga or 18F in dissected tissue was determined.

Results: Within 1 h, high uptake of the 68Ga-labeled peptide in the tumor lesions (23.4 ± 7.2% ID/g) and low background activity levels were observed (e.g., tumor-to-intestine ratio, 58 ± 22). This resulted in a clear visualization of all intra-abdominal tumor lesions ≥ 10 μL and even some tumors as small as 5 μL (2 mm diameter). 18F-FDG efficiently localized in the tumors (8.7 ± 3.1% ID/g) but also showed physiological uptake in various normal tissues (e.g., tumor-to-intestine ratio, 3.9 ± 1.1).

Conclusions: Pretargeted immuno-PET with bsmAb and a 68Ga-labeled peptide could be a very sensitive imaging method for imaging colonic cancer, disclosing occult lesions.

No MeSH data available.


Related in: MedlinePlus