Application of the phase-space distribution approach of Monte Carlo for radiation contamination dose estimation from the (n,γ), (γ,n) nuclear reactions and linac leakage photons in the megavoltage radiotherapy facility

AimThe aim of this study was to characterize the radiation contamination inside and outside the megavoltage radiotherapy room.BackgroundRadiation contamination components in the 18 MV linac room are the secondary neutron, prompt gamma ray, electron and linac leakage radiation.Materials and MethodsAn 18 MV linac modeled in a typical bunker employing the MCNPX code of Monte Carlo. For fast calculation, phase-space distribution (PSD) file modeling was applied and the calculations were conducted for the radiation contamination components dose and spectra at 6 locations inside and outside the bunker.ResultsThe results showed that the difference of measured and calculated percent depth-dose (PDD) and photo beam-profile (PBP) datasets were lower than acceptable values. At isocenter, the obtained photon dose and neutron fluence were 2.4 × 10⁻¹⁴ Gy/initial e° and 2.22 × 10^-8 n°/cm², respectively. Then, neutron apparent source strength (Q_N) value was found as 1.34 × 10¹² n°/Gy X at isocenter and the model verified to photon and neutron calculations. A surface at 2 cm below the flattening filter was modeled as phase-space (PS) file for PDD and PBP calculations. Then by use of a spherical cell in the center of the linac target as a PS surface, contaminant radiations dose, fluence and spectra were estimated at 6 locations in a considerably short time, using the registered history of all particles and photons in the 13GB PSD file as primary source in the second step.ConclusionDesigning the PSD file in MC modeling helps user to solve the problems with complex geometry and physics precisely in a shorter run-time.     

Eye lens dose correlations with personal dose equivalent and patient exposure in paediatric interventional cardiology performed with a fluoroscopic biplane system

PurposeTo analyse the correlations between the eye lens dose estimates performed with dosimeters placed next to the eyes of paediatric interventional cardiologists working with a biplane system, the personal dose equivalent measured on the thorax and the patient dose.MethodsThe eye lens dose was estimated in terms of H_p(0.07) on a monthly basis, placing optically stimulated luminescence dosimeters (OSLDs) on goggles. The H_p(0.07) personal dose equivalent was measured over aprons with whole-body OSLDs. Data on patient dose as recorded by the kerma-area product (P_KA) were collected using an automatic dose management system. The 2 paediatric cardiologists working in the facility were involved in the study, and 222 interventions in a 1-year period were evaluated. The ceiling-suspended screen was often disregarded during interventions.ResultsThe annual eye lens doses estimated on goggles were 4.13 ± 0.93 and 4.98 ± 1.28 mSv. Over the aprons, the doses obtained were 10.83 ± 0.99 and 11.97 ± 1.44 mSv. The correlation between the goggles and the apron dose was R² = 0.89, with a ratio of 0.38. The correlation with the patient dose was R² = 0.40, with a ratio of 1.79 μSv Gy⁻¹ cm⁻². The dose per procedure obtained over the aprons was 102 ± 16 μSv, and on goggles 40 ± 9 μSv. The eye lens dose normalized to P_KA was 2.21 ± 0.58 μSv Gy⁻¹ cm⁻².ConclusionsMeasurements of personal dose equivalent over the paediatric cardiologist’s apron are useful to estimate eye lens dose levels if no radiation protection devices are typically used.     

Radiation dose to patients and staff during angiography of the lower limbs. Derivation of local dose reference levels

BackgroundThe Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of reference dose levels (DRLs).PurposeTo perform measurements of the dose delivered during diagnostic angiography of the lower limbs using thermoluminescence dosimeters (TLDs), extraction of DRLs and estimation of the effective dose and radiation risk for this particular examination.MethodsDose measurement was performed on 30 patients by using TLD sachets attached in 5 different positions not only on the patient, but also to the radiologist. All the appropriate factors were recorded. Measurement of the ESD was performed after each examination.ResultsThe mean entrance skin dose (ESD) was calculated to be 70.8, 67.7, 24.3, 18.4, 9.7 mGy at the level of aorta bifurcation, pelvis, femur, knees, and at feet, respectively. The average effective dose is 9.8 mSv with the radiation risks for fatal cancer to be 5.4 × 10^?4. The effective dose of the radiologist was calculated to be 0.023 mSv per procedure.ConclusionRadiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and the difficulties in conducting procedures. The main reason for the increased patient dose, compared to other studies, is the number of frames rather than the duration of fluoroscopy. For DSA of the lower limbs, the DRL was chosen to be an entrance skin dose of 96.4 mGy in the pelvic region. The dose to the radiologist is negligible.     

Étude dosimétrique de préparations de médicaments radiopharmaceutiques au 68Ga

AimProduction of ⁶⁸Ga-radiopharmaceuticals is a rapidly growing field in France. However, operators may already be involved in other radiopharmaceutical activities. It is thus necessary to know the exposure of this new activity.Material and methodsFor passive dosimetry, a radiophotoluminescent (RPL) dosimeter, a thermoluminescent (TLD) chip, 2 TLD rings and a passive dosimeter for crystalline were used. For active dosimetry, an extremity dosimeter and a whole body dosimeter were used. This study was performed during semi-automatized production of ⁶⁸Ga-investigational medicinal products. Values were normalized to 500MBq manipulated (median activity using a 1850MBq ⁶⁸Ga-generator), 60 radiosynthesis (maximum enrollment ability of our center) and 2 operators. A LB123 proportional counter was used for quantification of external exposition to 10MBq ⁶⁸Ge and internal exposition by inhalation was theoretically assessed. ⁶⁸Ga emission attenuation by collective protection equipments was also discussed.ResultsConsidering passive dosimetry, the equivalent dose to extremities was 21.75 ± 0.34 mSv, the whole-body effective dose was 0.189 ± 0.011 mSv and the dose to crystalline was 0.925 ± 0.009 mSv. Considering active dosimetry, the equivalent dose to extremities was 8,75 ± 0.12 mSv and the whole-body effective dose was 0,088 ± 0.009 mSv. Total exposure to ⁶⁸Ge was 1.75 μSv.ConclusionIn our hands, ⁶⁸Ga is a directly transposable activity in radiopharmacies already equipped for ¹⁸F because of a dosimetry complying with regulatory limits and suitable radiation protection of collective equipments.     

Stereotactic body radiation therapy in hepatocellular carcinoma: Optimal treatment strategies based on liver segmentation and functional hepatic reserve

AimTo discuss current dosage for stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) patients and suggest alternative treatment strategies according to liver segmentation as defined by the Couinaud classification.BackgroundSBRT is a safe and effective alternative treatment for HCC patients who are unable to undergo liver ablation/resection. However, the SBRT fractionation schemes and treatment planning strategies are not well established.Materials and methodsIn this article, the latest developments and key findings from research studies exploring the efficacy of SBRT fractionation schemes for treatment of HCC are reviewed. Patients’ characteristics, fractionation schemes, treatment outcomes and toxicities were compiled. Special attention was focused on SBRT fractionation approaches that take into consideration liver segmentation according to the Couinaud classification and functional hepatic reserve based on Child–Pugh (CP) liver cirrhosis classification.ResultsThe most common SBRT fractionation schemes for HCC were 3 × 10–20 Gy, 4–6 × 8–10 Gy, and 10 × 5–5.5 Gy. Based on previous SBRT studies, and in consideration of tumor size and CP classification, we proposed 3 × 15–25 Gy for patients with tumor size <3 cm and adequate liver reserve (CP-A score 5), 5 × 10–12 Gy for patients with tumor sizes between 3 and 5 cm or inadequate liver reserve (CP-A score 6), and 10 × 5–5.5 Gy for patients with tumor size >5 cm or CP-B score.ConclusionsTreatment schemes in SBRT for HCC vary according to liver segmentation and functional hepatic reserve. Further prospective studies may be necessary to identify the optimal dose of SBRT for HCC.     

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy

PurposeIn scattering proton therapy, the beam incidence, i.e. the patient’s orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature.MethodsMCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size.ResultsUsing a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63 μGy Gy⁻¹ and 149 μGy Gy⁻¹ were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient’s orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5 times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence.ConclusionBeam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient.     

Concomitant chemo-radiotherapy for unresectable oesophageal cancer: A mono-institutional study on 40 patients

Background/AimTo analyse clinical response, overall (OS) and disease free survival (DFS) and toxicity in patients with unresectable oesophageal cancer treated by concomitant chemo-radiotherapy (CRT).Materials and methodsForty patients with stage IIa–IVa biopsy proven oesophageal carcinoma were treated with CRT. All patients were studied with endoscopy and CT and judged unresectable after multidisciplinary discussion. CRT consisted of 3 cycles of cisplatin 100 mg/m² or carboplatin 300 mg/m² on day 1 and 5-fluorouracil 1000 mg/m² as a continuous infusion of 96 h associated with concurrent 3D-conformal RT. By using 15 MeV X-rays, a total dose of 60–66 Gy was delivered with daily fractions of 1.8–2.0 Gy.ResultsComplete response (CR), partial response (PR) and no response (NR) were observed in 50%, 20% and 20% of cases, respectively. Of the 20 patients with CR, 15 developed loco-regional recurrent disease. OS and DFS rates at 3 and 5 years were 38%, 8%, 49% and 10%, respectively. Total radiation dose ≥60 Gy improved loco-regional control and complete response (CR vs. PR + NR; p = 0.004) influenced both DFS and loco-regional control. Grade 3 gastrointestinal and haematological acute toxicity occurred in 3/40 patients (7.5%). One patient developed grade 4 renal failure. Late toxicity was reported in 2/40 patients (5.0%), consisting of grade 3 radiation pneumonitis.ConclusionsConcomitant CRT for unresectable oesophageal cancer can result in an acceptable loco-regional control with limited toxicity. Response after treatment and total radiation dose influenced the outcome.     

Determination of initial electron parameters by means of Monte Carlo simulations for the Siemens Artiste Linac 6 MV photon beam

AimIn this study, we investigated initial electron parameters of Siemens Artiste Linac with 6 MV photon beam using the Monte Carlo method.BackgroundIt is essential to define all the characteristics of initial electrons hitting the target, i.e. mean energy and full width of half maximum (FWHM) of the spatial distribution intensity, which is needed to run Monte Carlo simulations. The Monte Carlo is the most accurate method for simulation of radiotherapy treatments.Materials and methodsLinac head geometry was modeled using the BEAMnrc code. The phase space files were used as input file to DOSXYZnrc simulation to determine the dose distribution in a water phantom. We obtained percent depth dose curves and the lateral dose profile. All the results were obtained at 100 cm of SSD and for a 10 × 10 cm² field.ResultsWe concluded that there existed a good conformity between Monte Carlo simulation and measurement data when we used electron mean energy of 6.3 MeV and 0.30 cm FWHM value as initial parameters. We observed that FWHM values had very little effect on PDD and we found that the electron mean energy and FWHM values affected the lateral dose profile. However, these effects are between tolerance values.ConclusionsThe initial parameters especially depend on components of a linac head. The phase space file which was obtained from Monte Carlo Simulation for a linac can be used as calculation of scattering, MLC leakage, to compare dose distribution on patients and in various studies.     

2,5-Diaryloxadiazoles and their precursors as novel inhibitors of cathepsins B,H and L

High levels of cathepsins indicated in various pathological conditions like arthritis, cancer progressions, and atherosclerosis explains the need to explore potential inhibitors of these proteases which can be of great therapeutic significance. We, in the present work, report the synthesis of some 2,5-diaryloxadiazoles from N-subsitutedbenzylidenebenzohydrazides. The synthesized compounds were screened for their inhibitory potential on cathepsins B, H and L. Structure Activity Relationship studies show that 2,5-diaryloxadiazoles were less inhibitory than their precursors. 1i and 2k have been found to be most inhibitory to cathepsins B and L. Their K_i values have been calculated as 11.38 × 10⁻⁸ M and 66.4 × 10⁻⁸ M for cathepsin B and 4.2 × 10⁻⁹ M and 47.31 × 10⁻⁹ M for cathepsin L, respectively. However, cathepsin H activity was maximally inhibited by compounds, 1e and 2c with K_i values of 4.4 × 10⁻⁷ M and 5.6 × 10⁻⁷ M, respectively. Enzyme kinetic studies suggest that these compounds are competitive inhibitors to the enzymes. The results have been compared with docking results obtained using iGemDock.     

Measurement of stray neutron doses inside the treatment room from a proton pencil beam scanning system

PurposeTo measure the environmental doses from stray neutrons in the vicinity of a solid slab phantom as a function of beam energy, field size and modulation width, using the proton pencil beam scanning (PBS) technique.MethodMeasurements were carried out using two extended range WENDI-II rem-counters and three tissue equivalent proportional counters. Detectors were suitably placed at different distances around the RW3 slab phantom. Beam irradiation parameters were varied to cover the clinical ranges of proton beam energies (100–220 MeV), field sizes ((2 × 2)–(20 × 20) cm²) and modulation widths (0–15 cm).ResultsFor pristine proton peak irradiations, large variations of neutron H¹(10)/D were observed with changes in beam energy and field size, while these were less dependent on modulation widths. H¹(10)/D for pristine proton pencil beams varied between 0.04 μSv Gy⁻¹ at beam energy 100 MeV and a (2 × 2) cm² field at 2.25 m distance and 90° angle with respect to the beam axis, and 72.3 μSv Gy⁻¹ at beam energy 200 MeV and a (20 × 20) cm² field at 1 m distance along the beam axis.ConclusionsThe obtained results will be useful in benchmarking Monte Carlo calculations of proton radiotherapy in PBS mode and in estimating the exposure to stray radiation of the patient. Such estimates may be facilitated by the obtained best-fitted simple analytical formulae relating the stray neutron doses at points of interest with beam irradiation parameters.     

Radiation therapy for the management of painful bone metastases: Results from a randomized trial

AimThe aim of this study was to compare the effectiveness of two radiotherapy schedules in patients with bone metastases.BackgroundWe analyzed the need for re-irradiation, rates of pain control, pathological fractures, and functionality in patients randomized to single-fraction (8 Gy 1×) or multiple-fraction radiotherapy (3 Gy 10×) with at least 12 months follow-up, during five years. The hypothesis was that the two radiotherapy schedules are equally effective.Materials and methodsNinety patients with painful skeletal metastases were randomized to receive single fraction (8 Gy) or multiple fraction (3 Gy 10×) radiotherapy.ResultsIn the single-fraction group, seven pathological fractures occurred (15.5%) versus two (4.4%) in the multiple-fraction group. There was no statistically significant difference between the time it took to suffer a pathological fracture in both groups (p = 0.099). Patients in the single-fraction group received twelve re-irradiations (26.6%), four in the multiple-fraction group (8.8%), with no significant difference between time elapsed before the first re-irradiation (p = 0.438).ConclusionThis study shows no difference between the two groups for the majority of patients with painful bone metastases. Patients were followed up during five years, and the trial showed no disadvantage for 8 Gy 1× compared to 3 Gy 10×. Despite the fact that the pathological fracture rate is 3.75 times higher in the single-fraction group, this schedule is considered more convenient for patients and more cost-effective for radiotherapy departments.     

Radiological protection for pregnant women at a large academic medical Cancer Center

PurposeMost radiation protection programs, regulations and guidance apply specific restrictions to the occupational exposure of pregnant workers. The aim of this study was to compile data from the declared pregnant woman (DPW) radiation protection program over more than 5 years at a large, high-volume, comprehensive oncology academic/medical institution and to evaluate for effectiveness against existing regulations and guidance.MethodsA retrospective review was performed of the data collected as part of the DPW radiation protection program from January 2010 through May 2016, including the number of declared pregnancies, worker category, personal and fetal dosimetry monitoring measurements, workplace modifications, as well as the monthly and total recorded badge results during the entire pregnancy.Results245 pregnancies were declared. The mean monthly fetal radiation dosimetry result was 0.009 mSv with a median of 0.005 mSv and a maximum of 0.39 mSv. The mean total dose over the entire pregnancy was estimated to be 0.08 mSv with a median of 0.05 mSv and a maximum of 0.89 mSv. Only 8 (3.2%) of the 245 declared pregnancies required that workplace modifications be implemented for the worker.ConclusionsThe implementation of a declared pregnancy and fetal assessment program, careful planning, an understanding of the risks, and minimization of radiation dose by employing appropriate radiation safety measures as needed, can allow medical staff to perform procedures and normal activities without incurring significant risks to the conceptus, or significant interruptions of job activities for most medical workers.     

A multiple free-radical scavenging (MULTIS) study on the antioxidant capacity of a neuroprotective drug,edaravone as compared with uric acid,glutathione, and trolox

Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) is a neuroprotective drug that has been used for brain ischemia injury treatment. Because its activity is speculated to be due to free radical scavenging activity, we carried out a quantitative determination of edaravone’s free radical scavenging activity against multiple free radical species. Electron spin resonance (ESR) spin trapping-based multiple free-radical scavenging (MULTIS) method was employed, where target free radicals were hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen. Edaravone showed relatively high scavenging abilities against hydroxyl radical (scavenging rate constant k = 2.98 × 10¹¹ M⁻¹ s⁻¹), singlet oxygen (k = 2.75 × 10⁷ M⁻¹ s⁻¹), and methyl radical (k = 3.00 × 10⁷ M⁻¹ s⁻¹). Overall, edaravone’s scavenging activity against multiple free radical species is as robust as other known potent antioxidant such as uric acid, glutathione, and trolox. A radar chart illustration of the MULTIS activity relative to uric acid, glutathione, and trolox indicates that edaravone has a high and balanced antioxidant activity with low specificity.     

Possibility of limiting the un-justified irradiation in 131I therapy of Graves' disease: A thyroid mass-reduction based method for the optimum activity calculation

ObjectiveIn Graves' disease therapy, the amount of ¹³¹I is usually decided following two different modalities: the administration of a fixed activity or of an activity individually calculated based on a fixed value of target absorbed dose. Although the effectiveness of each of these approaches is good (about 80% of patients cured), the ALARA principle must be applied avoiding the un-justified radioactivity to the patient himself, the people living/working near him and the environment. In this paper a new approach to the ¹³¹I therapy in Graves' disease, based on the optimum value of the final thyroid mass, is presented.Design97 Graves' disease patients (29 males) were randomly assigned into three groups (GR1, GR2, GR3). In two of them (GR1, GR3) the radioiodine administering activity was calculated based on two fixed thyroid absorbed dose values (100 Gy for GR1; 400 Gy for GR3), in GR2 it was calculated based on the desired final optimum thyroid mass value m_f = 0.24 m₀/U₀ResultsThe rate of cured patients are 48% (GR1), 97% (GR2) (z-test, p < 0.001) and 97% (GR3). The average activity administered to GR2 (393 ± 157 MBq) is lower than that administrered to GR3 patients (524 ± 201 MBq) (p = 0.007, two-tails unpaired t-test); the thyroid absorbed dose in GR2 (262 ± 78 Gy) is lower than in GR3 patients (407 ± 23 Gy) (p < 0.001, two-tails unpaired t-test).ConclusionOur results demonstrate that the thyroid-mass based approach optimizes the treatment avoiding an un-justified excess or a not-effective too low activity without time and resources consuming.     

A biosensor based on gold nanoparticles,dihexadecylphosphate, and tyrosinase for the determination of catechol in natural water

In this work, a biosensor using a glassy carbon electrode modified with gold nanoparticles (AuNPs) and tyrosinase (Tyr) within a dihexadecylphosphate film is proposed. Cystamine and glutaraldehyde crosslinking agents were used as a support for Tyr immobilization. The proposed biosensor was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and cyclic voltammetry in the presence of catechol. The determination of catechol was carried out by amperometry and presented a linear concentration range from 2.5 × 10⁻⁶ to 9.5 × 10⁻⁵ mol L⁻¹ with a detection limit of 1.7 × 10⁻⁷ mol L⁻¹. The developed biosensor showed good repeatability and stability. Moreover, this novel amperometric method was successfully applied in the determination of catechol in natural water samples. The results were in agreement with a 95% confidence level for those obtained using the official spectrophotometric method.     

Ecliptamines A–D,four new guanidine alkaloids from Eclipta prostrata L.

Four structurally unique guanidine alkaloids ecliptamines A–D (1–4) and one known analog (5) were isolated from the aerial parts of Eclipta prostrata (Asteraceae). Their structures were elucidated on the basis of spectroscopic analyses and chemical methods. The inhibitory activities of 1, 2 and 5 were assayed with respect to cyclooxygenase-1 (COX-1) and -2 (COX-2). Compound 5 showed moderate inhibitory activities against COX-1 and -2 with IC₅₀ values of 3.0 × 10⁻³ M and 8.3 × 10⁻⁴ M, respectively, whereas aspirin as a positive control displayed the IC₅₀ values of 4.2 × 10⁻⁴ M (against COX-1) and 7.1 × 10⁻⁴ M (against COX-2).     

Dosimetric characterization of small fields using a plastic scintillator detector: A large multicenter study

PurposeIn modern radiation therapy accurate small fields dosimetry is a challenge and its standardization is fundamental to harmonize delivered dose in different institutions. This study presents a multicenter characterization of MLC-defined small field for Elekta and Varian linear accelerators. Measurements were performed using the Exradin W1 plastic scintillator detector.Materials and methodsThe project enrolled 24 Italian centers. Each center performed Tissue Phantom Ratio (TPR), in-plane and cross-plane dose profiles of 0.8 × 0.8 cm² field, and Output Factor (OF) measurements for square field sizes ranging from 0.8 to 10 cm. Set-up conditions were 10 cm depth in water phantom at SSD 90 cm. Measurements were performed using two twin Exradin W1 plastic scintillator detectors (PSD) correcting for the Cerenkov effect as proposed by the manufacturer.ResultsData analysis from 12 Varian and 12 Elekta centers was performed. Measurements of 7 centers were not included due to cable problems. TPR measurements showed standard deviations (SD) < 1%; SD < 0.4 mm for the profile penumbra was obtained, while FWHM measurements showed SD < 0.5 mm. OF measurements showed SD < 1.5% for field size greater than 2 × 2 cm². Median OFs values were in agreement with the recent bibliography.ConclusionsHigh degree of consistency was registered for all the considered parameters. This work confirmed the importance of multicenter dosimetric intercomparison. W1 PSD could be considered as a good candidate for small field measurements.     

Investigation of Foscan® interactions with plasma proteins

The present study investigates the interaction of the second generation photosensitizer Foscan® with plasma albumin and lipoproteins. Spectroscopic studies indicated the presence of monomeric and aggregated Foscan® species upon addition to plasma protein solutions. Kinetics of Foscan® disaggregation in albumin-enriched solutions were very sensitive to the protein concentration and incubation temperature. Kinetic analysis demonstrated that two types of Foscan® aggregated species could be involved in disaggregation: dimers with a rate constant of k₁ = (2.30 ± 0.15) × 10⁻³ s⁻¹ and higher aggregates with rate constants varying from (0.55 ± 0.04) × 10⁻³ s⁻¹ for the lowest to the (0.17 ± 0.02) × 10⁻³ s⁻¹ for the highest albumin concentration. Disaggregation considerably increased with the temperature rise from 15 °C to 37 °C. Compared to albumin, Foscan® disaggregation kinetics in the presence of lipoproteins displayed poorer dependency on lipoprotein concentrations and smaller variations in disaggregation rate constants. Gel-filtration chromatography analysis of Foscan® in albumin solutions demonstrated the presence of aggregated fraction of free, non-bound to protein Foscan® and monomeric Foscan®, bound to protein.