Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 10;116(37):18590-18596.
doi: 10.1073/pnas.1906929116. Epub 2019 Aug 26.

Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study

Affiliations

Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study

Ardeshir R Rastinehad et al. Proc Natl Acad Sci U S A. .

Abstract

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

Keywords: MRI-ultrasound fusion; focal therapy; gold nanoshell; photothermal therapy; prostate cancer.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement: A.R.R. is the national principal investigator for the multiinstitutional trial of GSN-directed ablation, funded by Nanospectra Biosciences. He is also a consultant for Nanospectra Biosciences. J.L.W. and N.J.H. cofounded Nanospectra Biosciences in 2001 to transfer the photothermal therapeutics process from their labs into the clinic. They both have a small equity stake in this company but are not involved in any way with the company’s business or strategic decisions.

Figures

Fig. 1.
Fig. 1.
Boxplot comparing PSA(ng/ml) at baseline, 3, 6, and 12 mo after treatment. Wilcoxon signed ranks test compared with baseline PSA(ng/ml) at 3 mo (P = 0.001), at 6 mo (P = 0.002), and at 12 mo (P = 0.002).
Fig. 2.
Fig. 2.
Boxplot comparing International Prostate Symptom Score, urinary quality of life, and Sexual Health Inventory for Men scores at baseline, 1, 3, 6, and 12 mo.
Fig. 3.
Fig. 3.
Representative case of a 70-y-old man with focal prostate cancer treated successfully with GSN-directed laser excitation and ablation (AC) pretreatment, (D and E) 3 mo posttreatment. Follow-up biopsy at 3 mo was negative for cancer. (A) Axial T2-weighted image demonstrating left apex tumor Gleason 3+4 on targeted biopsy (arrow). (B) DWI image for b = 2,000 demonstrates restricted diffusion in tumor (hyperintensity compared to normal peripheral zone). (C) DCE-MRI parametric map (Ktrans/Ve) demonstrates increased enhancement of the tumor. (D) Axial T2-weighted image after treatment demonstrating contraction of ablation zone, appearing markedly hypointense, compatible with hemorrhagic/necrotic changes. (E) DWI image for b = 2,000 demonstrates resolution of restricted diffusion in treated tumor (arrow). (F) DCE-MRI parametric map (Ktrans/Ve) demonstrates resolution of abnormal enhancement in treated tumor (arrow). (Scale bar: 1 cm.)
Fig. 4.
Fig. 4.
Axial T2-weighted image of the prostate with the laser catheter (yellow arrow) within 2 mm of urethra (blue arrow) with sparing of the tissue. (Scale bar: 1 cm.)
Fig. 5.
Fig. 5.
Transperineal approach. (A) An axial view of the prostate ablation zone and the nearby urethra and rectum overlaid with a rectangular transperineal grid (3-mm spacing). The ablation zone is penetrated with the introducer trocars (red) through the targeting grid, allowing for the 4- to 5-mm treatment radius(tan). (B) Laser introducers (orange hub) placed with the thermocouple (black) through the transperineal grid. (C) UroNav MR/US Fusion guidance for trocar placement with real-time ultrasound imaging. 1. Live US and fusion image in which the purple horizontal line is the planned path for the trocars through the virtual target (ablation zone). 2. Pretreatment MRI denoting the prostate (purple), ablation zone region of interest. 3. Targeting screen allows planning for treatment and trocar placement. (Scale bar: B, 9 mm; C, 1 cm.)

Comment in

References

    1. Mie G., Articles on the optical characteristics of turbid tubes, especially colloidal metal solutions. Ann. Phys. Berlin 25, 377–445 (1908).
    1. Aden A. L., Kerker M., Scattering of electromagnetic waves from 2 concentric spheres. J. Appl. Phys. 22, 1242–1246 (1951).
    1. Neeves A. E., Birnboim M. H., Composite structures for the enhancement of nonlinear-optical susceptibility. J. Opt. Soc. Am. B 6, 787–796 (1989). - PubMed
    1. Averitt R. D., Sarkar D., Halas N. J., Plasmon resonance shifts of Au-coated Au2S nanoshells: Insight into multicomponent nanoparticle growth. Phys. Rev. Lett. 78, 4217–4220 (1997).
    1. Zhou H. S., Honma I., Komiyama H., Haus J. W., Controlled synthesis and quantum-size effect in gold-coated nanoparticles. Phys. Rev. B Condens. Matter 50, 12052–12056 (1994). - PubMed

Publication types

MeSH terms