Global population aging is unprecedented: the global population of children under age five is expected to fall by 49 million by midcentury, while the number of people over age 60 will grow by 1.2 billion, according to the United Nations. An aging population brings with it increased demands on healthcare systems. Governments have to reduce healthcare costs while maintaining quality of life. Today, illnesses are treated according to symptoms, but, in the future, with the help of lasers it will be possible to detect and cure illnesses before their critical phase and, hence, cut the high costs of hospitalization.
Screening and medical imaging methods based on photonics will strengthen preventive medicine and the early detection of diseases. Non-invasive or minimally invasive treatments, such as therapeutic laser systems, will help to improve patients’ quality of life and mobility.
Photochemical Internalization Helps in Cancer Therapy
Lasers are increasingly being deployed in the medical field from surgery to non-invasive therapeutic procedures. Semiconductor lasers are wavelength versatile and offer a high level of customization of the output power and beam delivery. One of the most recent application deploying lasers is cancer therapy using a unique photochemical drug delivery technology called photochemical internalization (PCI), developed and patented by PCI Biotech, Oslo, Norway.
PCI is a technology for light-directed intracellular drug delivery by triggered endosomal release. It was developed to introduce therapeutic molecules in a biologically active form specifically into diseased cells. This proprietary technology can provide local enhancement of a range of different drugs, including several cancer drugs currently in clinical use. An essential part of the treatment process is the single-wavelength multi-channel laser source that is used to activate the PCI process. The wavelength and the dose of the laser light in the treated tissue must be carefully controlled and requires designing and building a stable laser system at the desired 652nm photosensitizer wavelength.
PCI Biotech chose to use a medical laser system platform by Modulight, Tampere, Finland, for the PCI treatment process. This demanding treatment process set the bar even higher for an experienced laser system designer like Modulight and served as an excellent case study to assess the performance of state-of-the-art medical lasers.
PCI Biotech is focused on the clinical development of the proprietary photosensitizer Amphinex® in combination with cancer drugs for localized cancer treatment. Amphinex is currently developed in combination with the generic cytotoxic agent bleomycin for head and neck cancer and the generic cytotoxic agent gemcitabine for bile duct cancer. In addition, PCI Biotech has an ongoing pre-clinical program for the use of PCI to enhance the effect of vaccines, with an aim of starting a clinical study next year. A Phase I/II study of Amphinex in combination with bleomycin in cancer patients was completed at the University College Hospital in London, where 19 patients were treated. A strong response to treatment was seen in all patients, and Amphinex seems to be well tolerated.
In 2012, PCI Biotech started to include patients in a Phase II study of Amphinex induced PCI of bleomycin to treat head and neck cancer patients (the ENHANCE study). The ENHANCE study will include approximately 80 patients in 2012 and 2013, targeting patients with recurrent head and neck squamous cell carcinoma unsuitable for surgery and radiotherapy and without distant metastases. PCI Biotech aims to improve the patients’ quality of life, and prolong overall survival. In addition, the treatment may provide an excellent cosmetic outcome.
In Figure 1, a diagram shows that the photosensitizer Amphinex (s) locates to the membranes of intracellular endosomes. A drug (D) taken up by the normal cellular process called endocytosis is trapped in endosomes and can not reach the intracellular targets needed to elicit the therapeutic response. The integrity of the endosomal membrane is disrupted when Amphinex (s) is activated by 652 nm laser light, and the drug (D) can then escape the endosome and reach its intracellular target.
A Proof of Concept study for the use of PCI in patients with bile duct cancer will start in 2013. The Proof of Concept study will include up to 45 patients to assess the safety of Amphinex induced PCI of gemcitabine in patients with inoperable bile duct cancer, a patient population in great need of better treatment options.
Medical Laser System Requirements
Designing a versatile and reliable medical laser system platform requires a vast knowledge of the capabilities and limitations of laser technology, where most of the component solutions are not yet standardized. Furthermore, the whole design and manufacturing process should follow ISO13485 requirements and the system will be subject to a rigorous approval process confirming the safe use of the device. As a certified medical device manufacturer and fully integrated laser manufacturer, Modulight is combining its critical capabilities to build demanding medical laser devices like those needed for PCI treatment.
The PCI process requires fiber outputs to both invasive diffuser fibers (500 mW) and to a non-invasive frontal diffuser fiber (5W) and these channels should be individually addressable and calibratable. Modulight chose to use its LimeLight single-emitter subsystems as building blocks for the low power channels, whereas the high power 5W channel was realized separately. These subsystems are individually addressed by the control electronics and they self-maintain the optimal treatment parameters set by the calibration process, providing architectural distribution of control electronics inside the system. A unique design for the higher power channel (5W), enables very high stability at a very large operating power range, from less than 100mW to 5W. (See Figure 2)
Multi-channel Dose Calibration
Apart from multi-channel and wavelength requirements, many medical laser systems also require integrated calibration to measure the light dose radiated to the tissue. The dose is a combination of the laser power, treatment time, and tissue absorption and, therefore, requires an understanding of the tissue-light interaction. This is further complicated if varying length of diffuser fibers or illumination areas are used in the treatment. (See Figure 3)
The medical laser used houses an integrated calibration unit that allows easy dose calibration of single or multiple channels and for varying diffuser lengths from 1 to 5 cm. Calibration of multiple fibers together speeds up the treatment process but requires a careful analysis of the shadowing effects inside the calibration unit. In an invasive treatment process, the fibers are sterile and the whole calibration process has to maintain that even in the case of interrupted treatment and recalibration. The developed laser platform allows the use of a separate sterile cuvette protecting sterile fibers during the calibration process. The system also allows individual re-calibration of any channel, for example, in case of fiber breakage or contamination.
This medical laser platform supports a high-speed multi-channel treatment and calibration process. This ensures that treatment is safe and that patients are not subjected to unnecessary delays in the treatment process that, in many cases, requires invasive surgery. Shorter treatment and calibration times also result in significantly lower treatment costs because of the shorter use of expensive operating rooms and staffing.
■ Connecting Medical Laser Systems
Modulight is currently designing new platforms supporting therapeutic treatments over a range from visible blue (450 nm) to infrared wavelengths at 1,600 nm and beyond. The new system platforms will use a large area tablet-based user interface allowing easy treatment process guidance through high-definition graphics or even animation. The key design requirement is always safe and easy use of lasers in the healthcare process.
New features are being developed to allow easier safety control of the treatment and related consumables. Near-field radio frequency identification (RFID) is already a widely used technology in controlling logistics and the identification of many consumer products. Modulight further developed this technology to provide tools to control the use of approved combinations of drugs and consumables like sterile medical fibers that are critical for a safe treatment process. An integrated RFID module in a medical laser system allows for the immediate identification of an approved consumable through a wireless recognition process, and the automated set up of the system for the selected treatment parts as needed. By combining RFID functionality with an integrated wireless LAN module in a medical laser system, one can eventually track and monitor the use of consumables and their logistics globally through a centralized service center. The wireless connectivity also helps medical equipment manufacturers to actually monitor, diagnose, and service their systems remotely.
This article was written by Sampsa Kuusiluoma, Manager, New Product Introduction, Integrated Laser Solutions at Modulight, Tempere, Finland. For more information about Modulight and its laser technology, visit http://info.hotims.com/40439-166. For more information about PCI Biotech, visit http://www.pcibiotech.com.