Lothar Lilge

Princess Margaret Cancer Centre AND University of Toronto · Medical Biophysics

Ru(II) dyads derived from organic units that impart low-lying 3IL excited states combine the most attractive features of organic photosensitizers with those of coordination complexes. The result is a bichromophoric system with excited-state lifetimes that are significantly longer than those associated with traditional 3MLCT states. Incorporation of...

Metal-based photosensitizers are of interest as their absorption and chemical binding properties can be modified via the use of different ligands. Ru 2+ based photosensitizers are known to be effective photo-dynamic therapy (PDT) agents against bacteria, whereas use for oncological indications in vivo has not been demonstrated with the same level o...

Mammographic density (MD), associated with higher water and lower fat content in the breast, is strongly related to breast cancer risk. Optical attenuation spectroscopy (OS) is a non-imaging method of evaluating breast tissue composition by red and near-infrared light transmitted through the breast that, unlike mammography, does not involve radiati...

Risk assessment by parenchymal density pattern, a strong physical indicator of future breast cancer risk, is available with the onset of mammographic screening programmes. However, due to the use of ionizing radiation, mammography is not recommended for use in younger women, thereby rendering risk assessment unattainable at an earlier age. Visible...

This report is primarily concerned with methods for optical calibration of laser power for continuous wave (CW) light sources, predominantly used in photodynamic therapy (PDT). Light power calibration is very important for PDT, however, no clear standard has been established for the calibration procedure nor the requirements of power meters suitabl...

Traditional external light-based Photodynamic Therapy (PDT)’s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in penetrating deep-seated tumors. To address this, the emerging field of radiation-activated PDT (radioPDT) uses X-rays to trigger photosensitizer-containing nanoparticles (NPs). A ke...

Background: Socioeconomic status (SES) at birth is associated with breast cancer risk. Whether this association is driven by changes in breast tissue composition (BTC) prior to adulthood remains unclear. Methods: We used multivariable linear regression models to examine whether SES at birth is associated with BTC in adolescence and adulthood usi...

Background Breast density is a strong and potentially modifiable breast cancer risk factor. Almost everything we know about breast density has been derived from mammography, and therefore, very little is known about breast density in younger women aged <40. This study examines the acceptability and performance of two alternative breast density meas...

PDT-SPACE is an open-source software tool that automates interstitial photodynamic therapy treatment planning by providing patient-specific placement of light sources to destroy a tumor while minimizing healthy tissue damage. This work extends PDT-SPACE in two ways. The first enhancement allows specification of clinical access constraints on light...

Social environment may influence breast tissue composition and breast cancer risk through shaping risk factors operating in early life, adolescence, and adulthood. Socioeconomic status (SES) has been positively associated with breast cancer risk, and mammography studies in women in middle to late adulthood suggest the association might be mediated...

Photoacoustic imaging (PAI) is an evolving modality for studying and imaging tumor hypoxia. The experimental results from animals treated with ALA for Pre-PDT, Post-PDT, 4hr PDT, 24 hr PDT show a short-term increase in the BV followed by a strong decrease; however, no complete stasis. An alternate method is created by looking at the spatial and fre...

In vitro dose escalation experiments are one of the first gatekeepers in therapeutic evaluation and development. This also holds for evaluating novel photosensitizers (PS) and Photodynamic Therapy (PDT) co-therapies as needed to provide dose response guidelines before engaging in further pre-clinical studies. The dose needed to achieve 50% cell kil...

Ruthenium(II)-based coordination complexes have emerged as photosensitizers (PSs) for photodynamic therapy (PDT) in oncology as well as antimicrobial indications and have great potential. Their modular architectures that integrate multiple ligands can be exploited to tune cellular uptake and subcellular targeting, solubility, light absorption, and...

This study compared different approaches to measuring breast density and breast tissue composition (BTC) in adolescent girls (n = 42, aged 14–16 years) and their mothers (n = 39, aged 36–61 years) from a cohort in Santiago, Chile. Optical spectroscopy (OS) was used to measure collagen, water, and lipid concentrations, which were combined into a per...

Abstract Background Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural...

Background A phase 1b study of photosensitizer TLD-1433–mediated photodynamic therapy (PDT) was performed in bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients. Objective The primary objectives were safety and tolerability of PDT, with secondary objectives of (1) pharmacokinetic (PK) properties of TLD-1...

Significance: Open-source software packages have been extensively used in the past three decades in medical imaging and diagnostics, aiming to study the feasibility of the application ex vivo. Unfortunately, most of the existing open-source tools require some software engineering background to install the prerequisite libraries, choose a suitable...

Mammographic breast density is a strong breast cancer risk factor, and its routine clinical measurement could potentially be used to identify women at higher risk of breast cancer and/or monitor primary prevention strategies. Previous reports of optical breast spectroscopy (OBS), a novel approach to measuring breast density, demonstrated that it is...

Spinal metastases often occur in the advanced stages of breast, lung or prostate cancer, resulting in a significant impact on the patient’s quality of life. Current treatment modalities for spinal metastases include both systemic and localized treatments that aim to decrease pain, improve mobility and structural stability, and control tumour growth...

With the continued development of non-toxic photosensitizer drugs, interstitial photodynamic therapy (iPDT) is showing more favorable outcomes in recent clinical trials. IPDT planning is crucial to further increase the treatment efficacy. However, it remains a major challenge to generate a high-quality, patient-specific plan due to uncertainty in t...

The study presented a Monte Carlo simulation of light transport in 8 commonly used filtered facepiece respirators (FFRs) to assess the efficacy of UV at 254 nm for the inactivation of SARS-CoV-2. The results showed different fluence rates across the thickness of the 8 different FFRs, implying that some FFR models may be more treatable than others,...

Background : Isolated lung metastases in sarcoma and colorectal cancer patients are inadequately treated with current standard therapies. In Vivo Lung Perfusion, a novel platform, could overcome limitations to photodynamic therapy treatment volumes by using low cellular perfusate, removing blood, theoretically allowing greater light penetration. To...

Interstitial photodynamic therapy (iPDT) has shown promising results recently as a minimally invasive stand-alone or intra-operative cancer treatment. The development of non-toxic photosensitizing drugs with improved target selectivity has increased its efficacy. However, personalized treatment planning that determines the number of photon emitters...

Introduction: photobiomodulation was showed positive effects on bone healing, however, several studies search safe protocols and dosimetry, beyond good experimental models. Thus, the present study aimed to conduct a systematic review of photobiomodulation (PBM) effects on bone healing increase, focusing on animal experimental models. Revision: the...

Access to sterile personal protective equipment, in particular for filtered face respirators is critical in the current pandemic for front line healthcare workers. Extended use may be required during supply shortages or due to economic considerations. UVC sterilization can be a cost‐effective technique capable of high throughput. The suitability of...

This study presents numerical simulations of UVC light propagation through seven different filtered face respirators (FFR) to determine their suitability for UV germicidal inactivation (UVGI). UV propagation was modelled using the FullMonte program for two external light illuminations. The optical properties of the dominant three layers were determ...

Polycyclic aromatic hydrocarbons (PAH) are common environmental pollutants that result from incomplete combustion of biomass and fossil fuels. PAH have endocrine-disrupting properties and are known animal carcinogens. Evidence from case-control studies suggests an association between PAH and breast cancer risk, but longitudinal research on PAH expo...

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This study presents numerical simulations of UVC light propagation through seven different filtered face respirators (FFR) to determine their suitability for UV germicidal inactivation (UVGI). UV propagation was modelled using the FullMonte program for two external light illuminations. The optical properties of the dominant three layers were determ...

Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradien...

Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradie...

We present an optimized light diffuser placement algorithm for high-quality interstitial photodynamic therapy planning. We simulate the algorithm on modeled glioblas-toma multiforme cases. Results show damage to organs-at-risk is reduced by 46%-77% on average.

The purpose of this study was to investigate the effects that photobiomodulation therapy might produce in cells, in particular, related to their structure. Thus, this paper presents the results of morphological changes in fibroblasts following low-intensity light illumination. Mouse fibroblasts were grown on glass coverslips on either 4 kPa or 16 k...

TLD1433, a Ru(II) polypyridyl complex, was recently introduced. It can be activated in the 520 to 540 nm range. Here we report on the use of TLD1433 for the treatment of bladder carcinomas in vitro and in an in vivo orthotopic model. The electrostatic properties of the normal urothelium versus a tumour compromised urothelium provide for a high sele...

Background: Malignant gliomas are highly invasive and extremely difficult to treat tumours with poor prognosis and outcomes. Photodynamic therapy (PDT), mediated by Gleolan®, has been studied previously with partial success in treating these tumours and extending lifetime. We aim to determine whether combining PDT using ALA-protoporphyrin IX (PpIX...

Optimizing light delivery for photodynamic therapy, quantifying tissue optical properties or reconstructing 3D distributions of sources in bioluminescence imaging and absorbers in diffuse optical imaging all involve solving an inverse problem. This can require thousands of forward light propagation simulations to determine the parameters to optimiz...

Background Glioblastoma is an aggressive brain cancer in adults with a grave prognosis, aggressive radio and chemotherapy provide only a 15 months median survival. Methods We evaluated the tolerability and efficacy of the Ruthenium-based photosensitizer TLD-1433 with apo-Transferrin (Rutherrin) in the rat glioma 2 (RG2) model. The specific tumour...

Plasma-mediated ablation by ultrafast pulses is generally considered to be a material-independent process. We show that, in certain circumstances, this assumption may be invalid. Physical processes involved and the impact on applications are discussed.

Photophysical and in vitro photocytotoxicity studies were performed for the photosensitizer Dimegine, a disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX with very low systemic toxicity. The singlet oxygen and luminescence quantum yield were ΦΔ = 0,65 ± 0,06, and Φƒ=0,11 ± 0,01 respectively, and were independent of the excitation wavelen...

Transition metal complexes are of increasing interest as photosensitizers in photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In recent years, Ru(II) polypyridyl complexes have emerged as promising systems for both PDT and PCT. Their rich photochemical and photophysical properties derive from a variety of excited-state el...

Interstitial photodynamic therapy (iPDT) has shown promise recently as a minimally invasive cancer treatment, partially due to the development of non‐toxic photosensitizers in the absence of activation light. However, a major challenge in iPDT is the pre‐treatment planning process that specifies the number of diffusers needed, along with their posi...

We introduce the FullMonte tetrahedral 3-D Monte Carlo (MC) software package for simulation, visualization, and analysis of light propagation in heterogeneous turbid media including tissue. It provides the highest computational performance and richest set of input, output, and analysis facilities of any open-source tetrahedral-mesh MC light simulat...

During PDT disruption of cell respiration and metabolic changes could be one of the first events. Photophysical characteristics of the photosensitizer (PS) and its specific redox potential define consumption of molecular oxygen followed by generation of reactive oxygen species (ROS). The potential photosensitizer TLD1433 is based on transition meta...

Background The Pakistani Salt Range has a rich floral diversity including Withania coagulans from the Solanaceae family. Methods The crude methanolic extracts of the root, leaf, leaf stalk, and fruit of this plant were screened for their cytotoxic activity against human (HeLa, MCF-7, RD) and rat (RG2 and INS-1) cancer cell lines at 20 μg/mL and co...

Finding a high-quality treatment plan is an essential, yet difficult, stage of Photodynamic therapy (PDT) as it will determine the therapeutic efficacy in eradicating malignant tumors. A high-quality plan is patient-specific, and provides clinicians with the number of fiber-based spherical diffusers, their powers, and their interstitial locations t...

To improve a cancer patient's quality of life, short treatment duration resulting in rapid tumour removal while sparing normal tissue are highly desirable. Photodynamic therapy (PDT) commonly applied in a single treatment, while often effective can be limited at low photosensitizer or light doses. Combination therapies can overcome the efficacy lim...

Treatment planning for high efficacy therapy must be based on the photodynamic dose delivered and the intrinsic sensitivity of the target and host tissues. A Monte Carlo approach utilizing the Photodynamic Threshold model is presented

Tumor heterogeneity can be elucidated by mapping subregions of the lesion with differential imaging characteristics, called habitats. Dynamic Contrast Enhanced (DCE-)MRI can depict the tumor microenvironments by identifying areas with variable perfusion and vascular permeability, since individual tumor habitats vary in the rate and magnitude of the...