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Enhanced Therapeutic Epidermal Growth Factor Receptor (EGFR) Antibody Delivery via Pulsed Ultrasound with Targeting Microbubbles for Glioma Treatment.

Liao AH, Chou HY, Hsieh YL, Hsu SC, Wei KC, Liu HL - J Med Biol Eng (2015)

Bottom Line: Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment.The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs.Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, 106 Taiwan.

ABSTRACT

Pulsed-mode ultrasound (pUS) in combination with intravenously (IV) administered microbubbles (MBs) can enhance local drug delivery by temporarily enhancing capillary permeability. This study evaluates the use of epidermal growth factor receptor (EGFR)-targeting MBs after pUS treatment to enhance the effects of therapeutic-EGFR antibody delivery to glioma tumor cells in mice. Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment. All animals were analyzed using high-frequency small-animal US imaging. The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs. Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05). The final relative tumor volumes were 2664, 700, and 188 mm(3) for non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment, respectively. pUS treatment prolonged the mean circulatory halftime of targeting MBs and enhanced the anti-tumor effect of EGFR antibodies in a human glioma model in mice. Targeting MBs combined with pUS treatment thus has potential for enhanced therapeutic antibody delivery for facilitating anti-glioma treatment.

No MeSH data available.


Related in: MedlinePlus

Contrast-enhanced US images of non-targeting MBs (top row), targeting MBs (middle row), and targeting MBs combined with pUS treatment (bottom row) at various times
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Fig5: Contrast-enhanced US images of non-targeting MBs (top row), targeting MBs (middle row), and targeting MBs combined with pUS treatment (bottom row) at various times

Mentions: B-mode US images showed similar intensities before (pre-contrast) and after injection of MBs (Fig. 4a, c). However, the image intensity in nonlinear contrast mode was significantly higher after MB injection compared to that in pre-contrast images (Fig. 4b, d). Therefore, nonlinear contrast mode US imaging was used to investigate the accumulation of non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment (Fig. 5). Image enhancement was lower in pre-contrast images (Fig. 5, column denoted as “pre”) compared to that in images of injected targeting or non-targeting MBs (Fig. 5, column denoted as “0”). Ten min after MB injection, image enhancement was still obvious for targeting MBs and targeting MBs with pUS treatment compared to that of non-targeting MBs. TICs were acquired for 20 min (Fig. 6) and used to calculate perfusion parameters (Table 1). The ratios of the perfusion parameters of the targeting and pUS-treated groups relative to that of the non-targeted MB group are shown in Table 2. The PI of non-targeting MBs was higher than those of the other two groups. However, the TP, HT, PW, and AUC values of targeting MBs with pUS treatment were higher than those of the other two groups. Thus, increased vascular permeability was observed for targeting MBs with pUS treatment. The DS of targeting MBs with pUS treatment was more moderate compared to those of the other two groups.Fig. 4


Enhanced Therapeutic Epidermal Growth Factor Receptor (EGFR) Antibody Delivery via Pulsed Ultrasound with Targeting Microbubbles for Glioma Treatment.

Liao AH, Chou HY, Hsieh YL, Hsu SC, Wei KC, Liu HL - J Med Biol Eng (2015)

Contrast-enhanced US images of non-targeting MBs (top row), targeting MBs (middle row), and targeting MBs combined with pUS treatment (bottom row) at various times
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4414932&req=5

Fig5: Contrast-enhanced US images of non-targeting MBs (top row), targeting MBs (middle row), and targeting MBs combined with pUS treatment (bottom row) at various times
Mentions: B-mode US images showed similar intensities before (pre-contrast) and after injection of MBs (Fig. 4a, c). However, the image intensity in nonlinear contrast mode was significantly higher after MB injection compared to that in pre-contrast images (Fig. 4b, d). Therefore, nonlinear contrast mode US imaging was used to investigate the accumulation of non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment (Fig. 5). Image enhancement was lower in pre-contrast images (Fig. 5, column denoted as “pre”) compared to that in images of injected targeting or non-targeting MBs (Fig. 5, column denoted as “0”). Ten min after MB injection, image enhancement was still obvious for targeting MBs and targeting MBs with pUS treatment compared to that of non-targeting MBs. TICs were acquired for 20 min (Fig. 6) and used to calculate perfusion parameters (Table 1). The ratios of the perfusion parameters of the targeting and pUS-treated groups relative to that of the non-targeted MB group are shown in Table 2. The PI of non-targeting MBs was higher than those of the other two groups. However, the TP, HT, PW, and AUC values of targeting MBs with pUS treatment were higher than those of the other two groups. Thus, increased vascular permeability was observed for targeting MBs with pUS treatment. The DS of targeting MBs with pUS treatment was more moderate compared to those of the other two groups.Fig. 4

Bottom Line: Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment.The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs.Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, 106 Taiwan.

ABSTRACT

Pulsed-mode ultrasound (pUS) in combination with intravenously (IV) administered microbubbles (MBs) can enhance local drug delivery by temporarily enhancing capillary permeability. This study evaluates the use of epidermal growth factor receptor (EGFR)-targeting MBs after pUS treatment to enhance the effects of therapeutic-EGFR antibody delivery to glioma tumor cells in mice. Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment. All animals were analyzed using high-frequency small-animal US imaging. The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs. Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05). The final relative tumor volumes were 2664, 700, and 188 mm(3) for non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment, respectively. pUS treatment prolonged the mean circulatory halftime of targeting MBs and enhanced the anti-tumor effect of EGFR antibodies in a human glioma model in mice. Targeting MBs combined with pUS treatment thus has potential for enhanced therapeutic antibody delivery for facilitating anti-glioma treatment.

No MeSH data available.


Related in: MedlinePlus