Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation.
The content and structure of collagen is essential in governing the delivery of therapeutic molecules in tumors. Thus, simple histological staining of tumor tissue biopsies for collagen could be used to assess the accessibility of molecular therapeutics in tumors. Here we show that it is possible to optically image fibrillar collagen in tumors growing in mice using second-harmonic generation (SHG). Using this noninvasive technique, we estimated relative diffusive hindrance, quantified the dynamics of collagen modification after pharmacologic intervention and provided mechanistic insight into improved diffusive transport induced by the hormone relaxin. This technology could offer basic scientists and clinicians an enhanced ability to estimate the relative penetrabilities of molecular therapeutics.
Brown
Edward
E
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
McKee
Trevor
T
diTomaso
Emmanuelle
E
Pluen
Alain
A
Seed
Brian
B
Boucher
Yves
Y
Jain
Rakesh K
RK
D000818:Animals; D017364:Collagenases / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D024022:Fibrillar Collagens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012065:Relaxin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D024022:Fibrillar Collagens; D012065:Relaxin; D004549:Elastin; D017364:Collagenases; C417249:collagenase 1