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A novel fluorescent imaging agent for diffuse optical tomography of the breast: first clinical experience in patients.

van de Ven S, Wiethoff A, Nielsen T, Brendel B, van der Voort M, Nachabe R, Van der Mark M, Van Beek M, Bakker L, Fels L, Elias S, Luijten P, Mali W - Mol Imaging Biol (2009)

Bottom Line: Lesion location on DOT showed excellent agreement with MRI.Optimal lesion-to-background signals were obtained after 8 h.No adverse events occurred.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands. s.m.w.y.vandeven-2@umcutrecht.nl

ABSTRACT

Purpose: This is the first clinical evaluation of a novel fluorescent imaging agent (Omocianine) for breast cancer detection with diffuse optical tomography (DOT).

Procedures: Eleven women suspected of breast cancer were imaged with DOT at multiple time points (up to 24 h) after receiving an intravenous injection of Omocianine (doses 0.01 to 0.1 mg/kg bodyweight). Breast MRI was obtained for comparison.

Results: Histopathology showed invasive cancer in ten patients and fibroadenoma in one patient. With the lowest dose of Omocianine, two of three lesions were detected; with the second dose, three of three lesions were detected; with the two highest doses, none of five lesions were detected. Lesion location on DOT showed excellent agreement with MRI. Optimal lesion-to-background signals were obtained after 8 h. No adverse events occurred.

Conclusions: Lowest doses of Omocianine performed best in lesion detection; DOT using a low-dose fluorescent agent is feasible and safe for breast cancer visualization in patients.

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Related in: MedlinePlus

Dye uptake over time for patient 2 and patient 5. The dye kinetics for patient 2 with mainly fatty breast tissue (BI-RADS density category 1) show lower uptake (reconstructed fluorescence signal) of the mirror image vs. the lesion, while for patient 5 with more glandular breast tissue (BI-RADS density category 3), the dye kinetics show similar uptake of the mirror image vs. the lesion.
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Fig3: Dye uptake over time for patient 2 and patient 5. The dye kinetics for patient 2 with mainly fatty breast tissue (BI-RADS density category 1) show lower uptake (reconstructed fluorescence signal) of the mirror image vs. the lesion, while for patient 5 with more glandular breast tissue (BI-RADS density category 3), the dye kinetics show similar uptake of the mirror image vs. the lesion.

Mentions: The other important limitation in this study was that Omocyanine is a non-specific contrast agent. Ideally, this fluorescent probe would accumulate at the tumor site by extravasation through leaky vessels. However, since it does not specifically bind to a cancer-associated target, enhancement of other normal tissues is also possible. This non-specific enhancement pattern was observed when comparing the uptake of the contrast agent over time for the lesion and mirror images in different patients. Differences were noted between patients whose breasts contained mostly fatty tissue and patients whose breasts contained mostly glandular (heterogeneously dense) tissue. To illustrate this observation, two examples are shown in Fig. 3. As shown in the graphs, uptake of the contrast agent was much lower in fatty tissue (patient 2) than in glandular tissue (patient 5) if the lesion is compared to the mirror image location. In the patients with a high content of glandular tissue in their breasts, the uptake at the mirror image site vs. the background was quite similar to the uptake at the lesion site vs. the background. Although the sample size is small and we should be cautious in generalizing these observations, it indicates that the distinction between glandular and malignant tissue could be problematic with this non-specific fluorescent contrast agent. Clearly, there is a need for target-specific fluorescent agents to be tested in patient studies using an optical imaging device.Fig. 3


A novel fluorescent imaging agent for diffuse optical tomography of the breast: first clinical experience in patients.

van de Ven S, Wiethoff A, Nielsen T, Brendel B, van der Voort M, Nachabe R, Van der Mark M, Van Beek M, Bakker L, Fels L, Elias S, Luijten P, Mali W - Mol Imaging Biol (2009)

Dye uptake over time for patient 2 and patient 5. The dye kinetics for patient 2 with mainly fatty breast tissue (BI-RADS density category 1) show lower uptake (reconstructed fluorescence signal) of the mirror image vs. the lesion, while for patient 5 with more glandular breast tissue (BI-RADS density category 3), the dye kinetics show similar uptake of the mirror image vs. the lesion.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864903&req=5

Fig3: Dye uptake over time for patient 2 and patient 5. The dye kinetics for patient 2 with mainly fatty breast tissue (BI-RADS density category 1) show lower uptake (reconstructed fluorescence signal) of the mirror image vs. the lesion, while for patient 5 with more glandular breast tissue (BI-RADS density category 3), the dye kinetics show similar uptake of the mirror image vs. the lesion.
Mentions: The other important limitation in this study was that Omocyanine is a non-specific contrast agent. Ideally, this fluorescent probe would accumulate at the tumor site by extravasation through leaky vessels. However, since it does not specifically bind to a cancer-associated target, enhancement of other normal tissues is also possible. This non-specific enhancement pattern was observed when comparing the uptake of the contrast agent over time for the lesion and mirror images in different patients. Differences were noted between patients whose breasts contained mostly fatty tissue and patients whose breasts contained mostly glandular (heterogeneously dense) tissue. To illustrate this observation, two examples are shown in Fig. 3. As shown in the graphs, uptake of the contrast agent was much lower in fatty tissue (patient 2) than in glandular tissue (patient 5) if the lesion is compared to the mirror image location. In the patients with a high content of glandular tissue in their breasts, the uptake at the mirror image site vs. the background was quite similar to the uptake at the lesion site vs. the background. Although the sample size is small and we should be cautious in generalizing these observations, it indicates that the distinction between glandular and malignant tissue could be problematic with this non-specific fluorescent contrast agent. Clearly, there is a need for target-specific fluorescent agents to be tested in patient studies using an optical imaging device.Fig. 3

Bottom Line: Lesion location on DOT showed excellent agreement with MRI.Optimal lesion-to-background signals were obtained after 8 h.No adverse events occurred.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands. s.m.w.y.vandeven-2@umcutrecht.nl

ABSTRACT

Purpose: This is the first clinical evaluation of a novel fluorescent imaging agent (Omocianine) for breast cancer detection with diffuse optical tomography (DOT).

Procedures: Eleven women suspected of breast cancer were imaged with DOT at multiple time points (up to 24 h) after receiving an intravenous injection of Omocianine (doses 0.01 to 0.1 mg/kg bodyweight). Breast MRI was obtained for comparison.

Results: Histopathology showed invasive cancer in ten patients and fibroadenoma in one patient. With the lowest dose of Omocianine, two of three lesions were detected; with the second dose, three of three lesions were detected; with the two highest doses, none of five lesions were detected. Lesion location on DOT showed excellent agreement with MRI. Optimal lesion-to-background signals were obtained after 8 h. No adverse events occurred.

Conclusions: Lowest doses of Omocianine performed best in lesion detection; DOT using a low-dose fluorescent agent is feasible and safe for breast cancer visualization in patients.

Show MeSH
Related in: MedlinePlus