Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles

doi:10.1117/12.877780

. 2011 Feb 28:7902:79020F.

doi: 10.1117/12.877780.

Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles

Jae Youn Hwang¹, Zeev Gross², Harry B Gray³, Lali K Medina-Kauwe⁴, Daniel L Farkas⁵

Affiliations

¹ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA ; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA.
² Beckman Research Institute, California Institute of Technology, Pasadena, CA ; Department of Chemistry, Technion-Israel Institute of Technology, Haifa.
³ Beckman Research Institute, California Institute of Technology, Pasadena, CA.
⁴ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA ; Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
⁵ Department of Biomedical Engineering, University of Southern California, Los Angeles, CA ; Spectral Molecular Imaging, Inc., Beverly Hills CA.

PMID: 26412924
PMCID: PMC4582672
DOI: 10.1117/12.877780

Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles

Jae Youn Hwang et al. Proc SPIE Int Soc Opt Eng. 2011.

. 2011 Feb 28:7902:79020F.

doi: 10.1117/12.877780.

Authors

Jae Youn Hwang¹, Zeev Gross², Harry B Gray³, Lali K Medina-Kauwe⁴, Daniel L Farkas⁵

Affiliations

¹ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA ; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA.
² Beckman Research Institute, California Institute of Technology, Pasadena, CA ; Department of Chemistry, Technion-Israel Institute of Technology, Haifa.
³ Beckman Research Institute, California Institute of Technology, Pasadena, CA.
⁴ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA ; Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
⁵ Department of Biomedical Engineering, University of Southern California, Los Angeles, CA ; Spectral Molecular Imaging, Inc., Beverly Hills CA.

PMID: 26412924
PMCID: PMC4582672
DOI: 10.1117/12.877780

Abstract

We report the feasibility of tumor detection and delineation in vivo using multimode optical imaging of targeted gallium corrole (HerGa). HerGa is highly effective for targeted HER2+ tumor elimination in vivo, and it emits intense fluorescence. These unique characteristics of HerGa prompted us to investigate the potential of HerGa for tumor detection and delineation, by performing multimode optical imaging ex vivo and in vivo; the imaging modes included fluorescence intensity, spectral (including ratiometric), lifetime, and two-photon excited fluorescence, using our custom-built imaging system. While fluorescence intensity imaging provided information about tumor targeting capacity and tumor retention of HerGa, ratiometric spectral imaging offered more quantitative and specific information about HerGa location and accumulation. Most importantly, the fluorescence lifetime imaging of HerGa allowed us to discriminate between tumor and non-tumor regions by fluorescence lifetime differences. Finally, two-photon excited fluorescence images provided highly resolved and thus topologically detailed information around the tumor regions where HerGa accumulates. Taken together, the results shown in this report suggest the feasibility of tumor detection and delineation by multimode optical imaging of HerGa, and fluorescent chemotherapy agents in general. Specifically, the multimode optical imaging can offer complementary and even synergetic information simultaneously in the tumor detection and delineation by HerGa, thus enhancing contrast.

Keywords: Multimode optical imaging; fluorescence lifetime imaging microscopy (FLIM); spectral imaging; tumor detection; tumor targeted corrole; two-photon excitation.

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Figures

**Fig. 1. Imaging modes in multimode optical imaging system and specific features recommending each mode**

**Fig. 2**
Fluorescence intensity image of a mouse that received HerGa Following IV injection of HerGa, a fluorescence intensity image (A, left) and a photographic image (B, right) were obtained (excitation: 424nm and emission: 620nm). The arrows indicate tumor locations.

**Fig. 3. Spectrally classified image of a mouse that received HerGa IV injection**
(A) spectrally classified images were acquired using typical spectral imaging and analysis before (left) and at 1 day after HerGa IV injection (right). (B) spectral signatures of autofluorescence and HerGa. Red: HerGa, Green: autofluorescence. The arrow indicates tumor location.

**Fig. 4. Fluorescence lifetime image and a lifetime histogram of the mouse at 4 days after intravenous injection of HerGa**
(A) Fluorescence lifetime image of the mouse: a total of 25 images were acquired within 0 to 4800ps with a time step of 200ps. Then, a fluorescence lifetime image was constructed through a first-order exponential decay fit. (B) Lifetime histograms within the tumor and non-tumor regions selected by a solid and a dotted circle.

**Fig. 5. Two-photon excited fluorescence images of tumors**
The images of (A) tumor and (B) muscle were acquired using fs pulsed laser at 848nm, an emission filter with 620nm±60nm, Nikon 60x objective. Scale bar: 50μm.

See this image and copyright information in PMC

Cited by

Ultrafast electronic and vibrational dynamics in brominated aluminum corroles: Energy relaxation and triplet formation.
Stensitzki T, Yang Y, Berg A, Mahammed A, Gross Z, Heyne K. Stensitzki T, et al. Struct Dyn. 2016 May 12;3(4):043210. doi: 10.1063/1.4949363. eCollection 2016 Jul. Struct Dyn. 2016. PMID: 27226980 Free PMC article.
Biomedical Applications of Translational Optical Imaging: From Molecules to Humans.
Farkas DL. Farkas DL. Molecules. 2021 Nov 2;26(21):6651. doi: 10.3390/molecules26216651. Molecules. 2021. PMID: 34771060 Free PMC article. Review.

References

1. Lohrisch C, Piccart M. An overview of HER2. Seminars in Oncology. 2001;28(6 Suppl 18):3–11. - PubMed
1. Colombo M, Corsi F, Foschi D, Mazzantini E, Mazzucchelli S, Morasso C, Occhipinti E, Polito L, Prosperi D, Ronchi S, Verderio P. HER2 targeting as a two-sided strategy for breast cancer diagnosis and treatment: Outlook and recent implications in nanomedical approaches. Pharmacol Res. 2010;62(2):150–165. - PubMed
1. Medina-Kauwe LK, Maguire M, Kasahara N, Kedes L. Non-viral gene delivery to human breast cancer cells by targeted Ad5 penton proteins. Gene Therapy. 2001;8:1753–1761. - PubMed
1. Agadjanian H, Ma J, Rentsendorj A, Valluripalli V, Hwang JY, Mahammed A, Farkas DL, Gray HB, Gross Z, Medina-Kauwe LK. Tumor detection and elimination by a targeted gallium corrole. Proc Natl Acad Sci U S A. 2009;106(15):6105–6110. - PMC - PubMed
1. Hwang JY, Wachsmann-Hogiu S, Ramanujan VK, Nowatzyk AG, Koronyo Y, Medina-Kauwe LK, Gross Z, Gray HB, Farkas DL. Multimodal wide-field two-photon excitation imaging: characterization of the technique for in vivo applications. Biomedical Optics Express. 2011;2(2):356–364. - PMC - PubMed

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[1] Lohrisch C, Piccart M. An overview of HER2. Seminars in Oncology. 2001;28(6 Suppl 18):3–11. - PubMed

[2] Lohrisch C, Piccart M. An overview of HER2. Seminars in Oncology. 2001;28(6 Suppl 18):3–11. - PubMed

[3] Colombo M, Corsi F, Foschi D, Mazzantini E, Mazzucchelli S, Morasso C, Occhipinti E, Polito L, Prosperi D, Ronchi S, Verderio P. HER2 targeting as a two-sided strategy for breast cancer diagnosis and treatment: Outlook and recent implications in nanomedical approaches. Pharmacol Res. 2010;62(2):150–165. - PubMed

[4] Colombo M, Corsi F, Foschi D, Mazzantini E, Mazzucchelli S, Morasso C, Occhipinti E, Polito L, Prosperi D, Ronchi S, Verderio P. HER2 targeting as a two-sided strategy for breast cancer diagnosis and treatment: Outlook and recent implications in nanomedical approaches. Pharmacol Res. 2010;62(2):150–165. - PubMed

[5] Medina-Kauwe LK, Maguire M, Kasahara N, Kedes L. Non-viral gene delivery to human breast cancer cells by targeted Ad5 penton proteins. Gene Therapy. 2001;8:1753–1761. - PubMed

[6] Medina-Kauwe LK, Maguire M, Kasahara N, Kedes L. Non-viral gene delivery to human breast cancer cells by targeted Ad5 penton proteins. Gene Therapy. 2001;8:1753–1761. - PubMed

[7] Agadjanian H, Ma J, Rentsendorj A, Valluripalli V, Hwang JY, Mahammed A, Farkas DL, Gray HB, Gross Z, Medina-Kauwe LK. Tumor detection and elimination by a targeted gallium corrole. Proc Natl Acad Sci U S A. 2009;106(15):6105–6110. - PMC - PubMed

[8] Agadjanian H, Ma J, Rentsendorj A, Valluripalli V, Hwang JY, Mahammed A, Farkas DL, Gray HB, Gross Z, Medina-Kauwe LK. Tumor detection and elimination by a targeted gallium corrole. Proc Natl Acad Sci U S A. 2009;106(15):6105–6110. - PMC - PubMed

[9] Hwang JY, Wachsmann-Hogiu S, Ramanujan VK, Nowatzyk AG, Koronyo Y, Medina-Kauwe LK, Gross Z, Gray HB, Farkas DL. Multimodal wide-field two-photon excitation imaging: characterization of the technique for in vivo applications. Biomedical Optics Express. 2011;2(2):356–364. - PMC - PubMed

[10] Hwang JY, Wachsmann-Hogiu S, Ramanujan VK, Nowatzyk AG, Koronyo Y, Medina-Kauwe LK, Gross Z, Gray HB, Farkas DL. Multimodal wide-field two-photon excitation imaging: characterization of the technique for in vivo applications. Biomedical Optics Express. 2011;2(2):356–364. - PMC - PubMed

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Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles

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Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles

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