Inherently Multimodal Nanoparticle-Driven Tracking and Real-Time Delineation of Orthotopic Prostate Tumors and Micrometastases

Abstract

Prostate cancer is the most common cancer among men and the second cause of male cancer-related deaths. There are currently three critical needs in prostate cancer imaging to personalize cancer treatment: (1) accurate intraprostatic imaging for multiple foci and extra-capsular extent; (2) monitoring local and systemic treatment response and predicting recurrence; and (3) more sensitive imaging of occult prostate cancer bone metastases. Recently, our lab developed porphysomes, inherently multimodal, all-organic nanoparticles with flexible and robust radiochemistry. Herein, we validate the first in vivo application of 64Cu-porphysomes in clinically relevant orthotopic prostate and bony metastatic cancer models. We demonstrate clear multimodal delineation of orthotopic tumors on both the macro- and the microscopic scales (using both PET and fluorescence) and sensitively detected small bony metastases (<2 mm). The unique and multifaceted properties of porphysomes offers a promising all-in-one prostate cancer imaging agent for tumor detection and treatment response/recurrence monitoring using both radionuclide- and photonic-based strategies.

In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging

“…They have been used as fluorescence imaging 21 , positron emission tomography 22,23 , magnetic resonance imaging 24 and photoacoustic imaging 21,25 contrast agents, as well as for photodynamic therapy (PDT) 26 and photothermal therapy (PTT) 27 . As with the majority of nanoparticles intended for tumour targeting, the delivery of these porphyrin-based nanoparticles relies on the enhanced permeability and retention (EPR) effect, requiring on the order of hours to days for maximum accumulation.…”

“…a, pMBs and pNPs embedded in an acrylamide gel phantom were imaged using ultrasound(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) MHz transducer in contrast mode), photoacoustic (824 nm, 21 MHz transducer) and fluorescence (green excitation, 503 nm-548 nm; 560 nm long-pass detection) imaging. Samples: (1) phosphate buffered saline (PBS), (2) pMBs without applying ultrasound pulses (zero pulses), and after applying (3) one pulse, (4) three pulses and (5) ten pulses.…”

Porphysome nanoparticles: Tailoring treatments with nature’s pigments

“…Nuclear imaging has excellent tissue penetration and can be utilized for quantitative, wholebody imaging [82]. Liu et al [66,83], have reported the first forays into nuclear imaging with porphysomes, avoiding the need for exogenous chelators by inserting radioactive 64 Cu into the porphyrins that constitute the porphysome itself, leading to stable and accurate radiolabeling [66,83]. Iron containing porphysomes can be used to reversibly co-ordinate molecular oxygen, as previously mentioned, making high payload porphysomes attractive oxygen transporters [61].…”

Rethinking translational nanomedicine: insights from the ‘bottom-up’ design of the Porphysome for guiding the clinical development of imageable nanomaterials

“…Among the more impressive accomplishments with the 64 Cu-Porphysome in vivo include: their selective accumulation in tumorous tissues with low nonspecific accumulation in healthy tissues (excluding reticuloendothelial tissues) from 6 to 48 hours after intravenous administration, and their sensitive detection of micrometastases < 1-2-mm in size on both PET and fluorescence imaging (Figure 4a) [28,33,34]. systematically administered nanoparticle for enabling the dual-modal visualization and mapping of lymphatic drainage from the primary tumour to the sentinel lymph nodes.…”

“…500-mCi 64 Cu-Porphysomes 24 hours prior. Reprinted with permission from[33]. # 2013 American Chemical Society.…”