Ultrasound-guided intratumoral administration of collagenase-2 improved liposome drug accumulation in solid tumor xenografts
Zheng, X; Goins, BA; Cameron, IL; Santoyo, C; Bao, A; Frohlich, VC; Fullerton, GD
| HERO ID | 4850108 |
|---|---|
| In Press | No |
| Year | 2011 |
| Title | Ultrasound-guided intratumoral administration of collagenase-2 improved liposome drug accumulation in solid tumor xenografts |
| Authors | Zheng, X; Goins, BA; Cameron, IL; Santoyo, C; Bao, A; Frohlich, VC; Fullerton, GD |
| Journal | Cancer Chemotherapy and Pharmacology |
| Volume | 67 |
| Issue | 1 |
| Page Numbers | 173-182 |
| Abstract | <strong>PURPOSE: </strong>To investigate the effect of intratumoral administration of collagenase-2 on liposomal drug accumulation and diffusion in solid tumor xenografts.<br /><br /><strong>METHODS: </strong>Correlation between tumor interstitial fluid pressure (IFP) and tumor physiological properties (size and vessel fraction by B-mode and Doppler ultrasound, respectively) was determined. IFP response to intravenous or intratumoral collagenase-2 (0.1%) treatment was compared with intratumoral deactivated collagenase-2. To evaluate drug accumulation and diffusion, technetium-99 m-((99m)Tc)-liposomal doxorubicin (Doxil) was intravenously injected after collagenase-2 (0.1 and 0.5%, respectively) treatment, and planar scintigraphic images acquired and percentage of the injected dose per gram tissue calculated. Subsequently, tumors were subjected to autoradiography and histopathology.<br /><br /><strong>RESULTS: </strong>IFP in two-week-old head and neck squamous cell carcinoma xenografts was 18 ± 3.7 mmHg and not correlated to the tumor size but had reverse correlation with the vessel fraction (r = -0.91, P < 0.01). Intravenous and intratumoral collagenase-2 use reduced IFP by a maximum of 35-40%. Compared to the control, the low IFP level achieved through intratumoral route remained for a long period (24 vs. 2 h, P < 0.05). SPECT images and autoradiography showed significantly higher (99m)Tc-Doxil accumulation in tumors with intratumoral collagenase-2 treatment, confirmed by %ID/g in tumors (P < 0.05), and pathological findings showed extensive distribution of Doxil in tumors.<br /><br /><strong>CONCLUSIONS: </strong>Intratumoral injection of collagenase-2 could effectively reduce IFP in HNSCC xenografts for a longer period than using intravenous approach, which allowed for more efficient accumulation and homogeneous diffusion of the Doxil within the tumor interstitium. |
| Doi | 10.1007/s00280-010-1305-1 |
| Pmid | 20306263 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |