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Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.

Shuhendler AJ, Ye D, Brewer KD, Bazalova-Carter M, Lee KH, Kempen P, Dane Wittrup K, Graves EE, Rutt B, Rao J - Sci Rep (2015)

Bottom Line: The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents.To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported.Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.

ABSTRACT
Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.

No MeSH data available.


Related in: MedlinePlus

Interrogation of the relationship of C-SNAM MR signal enhancement with tumor volume change following radiation therapy.Tumor size change was measured as the fold-change in volume 4 days (black circles) or 13 days (red square) following the day of treatment administration (Fold-Volume Change). MR signal enhancement with C-SNAM was measured 2 days following tumor irradiation and was quantified as the hotspot %SE. Pearson’s correlation coefficients (r) are shown for day 4 and day 13 following treatment of the same group of animals. *p < 0.05 (Pearson’s r), n = 9.
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f5: Interrogation of the relationship of C-SNAM MR signal enhancement with tumor volume change following radiation therapy.Tumor size change was measured as the fold-change in volume 4 days (black circles) or 13 days (red square) following the day of treatment administration (Fold-Volume Change). MR signal enhancement with C-SNAM was measured 2 days following tumor irradiation and was quantified as the hotspot %SE. Pearson’s correlation coefficients (r) are shown for day 4 and day 13 following treatment of the same group of animals. *p < 0.05 (Pearson’s r), n = 9.

Mentions: Utilizing the optimal 2-day post-treatment time-point for a single imaging session of radiation-treated mice, the MR signal enhancement from C-SNAM was correlated with tumor treatment response (% tumor volume change) (Fig. 5). Tumor size was measured on the day of treatment administration, and then each day afterwards for 13 days (n = 9 mice). A significant correlation was observed between MR signal enhancement measured 2 days following radiation treatment and tumor volume change on both day 4 (black line, r = −0.92, Pearson correlation test, P < 0.05) and day 13 (red line, r = −0.71, Pearson correlation test, P < 0.05), representing early and late time points, respectively, in HeLa tumor growth. This negative correlation is expected since the higher the MRI signal produced by C-SNAM, the more caspase-3 activity, and the more tumor cell death and ensuing tumor growth reduction is expected. Therefore, the MR signal intensity from a single imaging session with C-SNAM within the optimal imaging window for therapy response monitoring is prognostic of the expected percent tumor volume change following therapy.


Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.

Shuhendler AJ, Ye D, Brewer KD, Bazalova-Carter M, Lee KH, Kempen P, Dane Wittrup K, Graves EE, Rutt B, Rao J - Sci Rep (2015)

Interrogation of the relationship of C-SNAM MR signal enhancement with tumor volume change following radiation therapy.Tumor size change was measured as the fold-change in volume 4 days (black circles) or 13 days (red square) following the day of treatment administration (Fold-Volume Change). MR signal enhancement with C-SNAM was measured 2 days following tumor irradiation and was quantified as the hotspot %SE. Pearson’s correlation coefficients (r) are shown for day 4 and day 13 following treatment of the same group of animals. *p < 0.05 (Pearson’s r), n = 9.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4594000&req=5

f5: Interrogation of the relationship of C-SNAM MR signal enhancement with tumor volume change following radiation therapy.Tumor size change was measured as the fold-change in volume 4 days (black circles) or 13 days (red square) following the day of treatment administration (Fold-Volume Change). MR signal enhancement with C-SNAM was measured 2 days following tumor irradiation and was quantified as the hotspot %SE. Pearson’s correlation coefficients (r) are shown for day 4 and day 13 following treatment of the same group of animals. *p < 0.05 (Pearson’s r), n = 9.
Mentions: Utilizing the optimal 2-day post-treatment time-point for a single imaging session of radiation-treated mice, the MR signal enhancement from C-SNAM was correlated with tumor treatment response (% tumor volume change) (Fig. 5). Tumor size was measured on the day of treatment administration, and then each day afterwards for 13 days (n = 9 mice). A significant correlation was observed between MR signal enhancement measured 2 days following radiation treatment and tumor volume change on both day 4 (black line, r = −0.92, Pearson correlation test, P < 0.05) and day 13 (red line, r = −0.71, Pearson correlation test, P < 0.05), representing early and late time points, respectively, in HeLa tumor growth. This negative correlation is expected since the higher the MRI signal produced by C-SNAM, the more caspase-3 activity, and the more tumor cell death and ensuing tumor growth reduction is expected. Therefore, the MR signal intensity from a single imaging session with C-SNAM within the optimal imaging window for therapy response monitoring is prognostic of the expected percent tumor volume change following therapy.

Bottom Line: The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents.To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported.Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Program at Stanford, Stanford, California 94305, USA.

ABSTRACT
Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.

No MeSH data available.


Related in: MedlinePlus