Roswell Park Comprehensive Cancer Center

Working in the Department of Cancer Genetics & Genomics in the Lab of Dr. Kent Nastiuk, I spent the summer testing novel targeted molecular imaging agents, including multiple sonophores (also called quenchers) , fluorophores (also called fluorescents) and dual labelled compounds for the detection of prostate cancer.

Background:

Prostate cancer is often over diagnosed and over treated due to the low specificity of the current prostate cancer screening test, circulating PSA or missed entirely on biopsy due to the low specificity of current imaging techniques. As such there is a need for new, non-invasive, higher specificity imaging methods for the detection of prostate cancer.

Photoacoustic imaging is a new biomedical imaging method that utilizes both ultrasound imaging and optical imaging. To do this near-infrared (NIR) imaging compounds are excited by high frequency laser pulses, generating ultrasonic waves. These ultrasonic waves are then detected by sensors to create scans in both 2D and 3D. The compounds can be conjugated to a targeting agent, specifically a urea inhibitor, DCL has been shown to effectively target PSMA (Dogra, 2016)

The use of NIR targeted molecular imaging agents in prostate cancer detection is safer than positron emission (PET) scans which require the use of a radioactive label, and greater specificity detecting tumors than ultrasound (US) or magnetic resonance (MRI) scans.

In addition to the single labelled fluorescents and quenchers, dual NIR compounds were tested. These combinations are theorized to utilize the Forster resonance energy transfer (FRET) mechanism to combine the signal of a fluorescent dye with a quencher dye component, thus giving a higher signal. According to FRET, the fluorescent signal can be maximized by the quencher absorbing the energy typically released as fluorescence by the fluorescent dye, subsequently releasing that energy as ultrasonic waves.

My Work:

I characterized the fluorescent and photoacoustic signals of the single labeled and dual labeled compounds. Proving that while there was no significant difference between the sonophores and the fluorophores on the LAZR, the dual labeled compounds provide a signal of 2 to 4 times higher PA signal. This is shown in the graph below (Lower Left).

I raised five prostate cancer cell lines to select a PSMA (+) cell line with a similar growth rate to our chosen PSMA (-) cell line, PC3. Ultimately CWR22Rv1 was selected for use in the cell stain trials.

I developed phantoms, to hold the cell pellets for imaging use the LAZR, though ultimately they were not used as they presented a barrier to detection since there was no photoacoustic barrier between the cells and the phantoms.

At the end of the internship I presented my work at the BNMC Biomedical Research Conference, as well as a poster symposium at Roswell Park. I also gave a layman's presentation and a scientific presentation to my peers at Roswell Park.