¹77Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. / Behandling av kastrasjonsresistent metastatisk prostatakreft med [¹77Lu]PSMA-radioligand.

Background: Treatment of castration-resistant metastatic prostate cancer with [¹77Lu]PSMA radioligand. Case presentation: A man in his seventies with metastatic prostate cancer received castration therapy for four years, developing castration-resistant disease. PET/CT with [68Ga]PSMA-11 showed high uptake in metastatic lymph nodes. The patient received 7.4 GBq [¹77Lu]PSMA-I&T (Curium, Finland) as five treatments at five-week intervals. Five weeks after the first treatment, p-PSA dropped from 154 to 53 µg/L. Five weeks after the fifth treatment, p-PSA was 1.8 µg/L. [68Ga]PSMA-11 PET/CT showed significant reduction in the size of metastases, with the largest decreasing in diameter from 10 to 4 mm. Seven months after the fifth treatment, p-PSA increased to 14.3 µg/L, and [68Ga]PSMA-11 PET/ CT revealed additional skeletal metastases, while the lymph node metastases remained unchanged. Thus, the treatment had a good but temporary effect on the metastases. Interpretation: Treatment with [¹77Lu]PSMA radioligand resulted in a temporary regression of the metastases.

Ultraviolet Exposure Scenarios: Balancing Risks of Erythema and Benefits of Cutaneous Vitamin D Synthesis.

Exposure to sunlight is a major source of vitamin D for most people. Yet public health advice has focused overwhelmingly on avoiding exposure of unprotected skin because of the risks of erythema and skin cancer. Given that there are also health risks associated with low vitamin D status, we explore the possibilities of achieving a range of targets associated with vitamin D and the accompanying erythema risk. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that a recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year, and for all the year at some (low) latitudes. We also show that such daily, sub-erythemal doses at lunchtime during the summer months is sufficient to avoid winter-time vitamin D deficiency for the UK all-weather climate, provided that lower arms and legs are exposed in the warmer months. At the higher proposed vitamin D dose of 1000 IU, lunchtime sun exposure is still a viable route to the vitamin but requires the commitment to expose greater areas of skin and is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.

Ultraviolet exposure scenarios: risks of erythema from recommendations on cutaneous vitamin D synthesis.

Exposure to sunlight is a major source of vitamin D for most people yet public health advice focuses overwhelmingly on avoiding exposure of unprotected skin because of the risks oferythema and skin cancer. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that the current recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year and for all the year at some (low) latitudes. At the higher proposed vitamin D dose of 1000 IU lunchtime sun exposure is still a viable route to the vitamin, but requires the commitment to expose greater areas of skin, or is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.

Traceable calibration with 177Lu and comparison of activity meters at hospitals in Norway and Sweden.

INTRODUCTION: The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on 177Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard. METHODS: Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with 177Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe. RESULTS: The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %. CONCLUSION: The activity of 177Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients.

Vitamin D-effective solar UV radiation, dietary vitamin D and breast cancer risk.

Vitamin D is well known for its important role in calcium and phosphor homeostasis. Recent research suggests that vitamin D also prevent some type of cancers. We studied solar vitamin D effective UV radiation (VD dose), dietary vitamin D, sun-seeking holidays, use of solarium, frequency of sunburn and breast cancer risk in a large population-based cohort study. A total of 41,811 women from the prospective Norwegian Women and Cancer Study, aged 40-70 years at baseline, were followed from 1997/1998 to 2007. Dietary vitamin D intake was calculated at baseline. Information on historical VD dose was used as a proxy for cutaneously obtained vitamin D status. Cox proportional hazards model was used. We adjusted for age, height, BMI, baseline menopausal status, use of hormone replacement therapy, use of oral contraception, alcohol, mother's history of breast cancer, mammography and parity. During 8.5 years of follow-up, 948 new cases of breast cancer were registered using data from the Norwegian Cancer Registry. We found no significant associations between VD dose, or vitamin D intake, or sun-seeking holidays, or use of solarium, or frequency of sunburn, and breast cancer risk. Relative risks (95% confidence intervals) for highest versus lowest category were 1.17 (0.95-1.44), 0.95 (0.75-1.21), 1.07 (0.87-1.32), 0.93 (0.76-1.14) and 1.10 (0.89-1.36), respectively. Our results do not support an association between vitamin D status, and breast cancer risk.

Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes.

BACKGROUND: The relationship between oral vitamin D supplementation and cutaneous photosynthesis is not well understood. OBJECTIVE: We sought to provide estimates of the equivalency of vitamin D production from natural sun exposure versus oral supplementation. METHODS: Using the FastRT simulation tool, we determined sun exposure times needed to achieve serum vitamin D(3) concentrations equivalent to 400 or 1000 IU vitamin D for individuals of various Fitzpatrick skin types living in Miami, FL, and Boston, MA, during the months of January, April, July, and October. RESULTS: Peak ultraviolet B irradiation for vitamin D synthesis occurs around 12 pm Eastern Standard Time (EST). In Boston, MA, from April to October at 12 pm EST an individual with type III skin, with 25.5% of the body surface area exposed, would need to spend 3 to 8 minutes in the sun to synthesize 400 IU of vitamin D. It is difficult to synthesize vitamin D during the winter in Boston, MA. For all study months in Miami, FL, an individual with type III skin would need to spend 3 to 6 minutes at 12 pm EST to synthesize 400 IU. Vitamin D synthesis occurs faster in individuals with lighter Fitzpatrick skin types. The duration to attain 1000 IU of vitamin D is longer in all scenarios. LIMITATIONS: Results of the computer model are only approximations. In addition, calculations were made based on the assumption that (1/4) of 1 minimal erythema dose directed at (1/4) body surface area is equal to 1000 IU of oral vitamin D. CONCLUSIONS: Although it may be tempting to recommend intentional sun exposure based on our findings, it is difficult, if not impossible to titrate one's exposure. There are well-known detrimental side effects of ultraviolet irradiation. Therefore, oral supplementation remains the safest way for increasing vitamin D status.

Duration of vitamin D synthesis from weather model data for use in prospective epidemiological studies.

In order to investigate the influence of solar radiation on vitamin D status and its association with different health outcomes in population based studies, appropriate estimates of the subjects' UV radiation exposure are needed. This unique study describes a method that estimates the daily number of vitamin D effective hours (VD-hours) at arbitrary ground locations throughout the period 1957-2002. The method is particularly suited for large-scale prospective epidemiological studies with questionnaire-based information on sun exposure, and where blood measures of vitamin D status are not available. The model takes total cloud cover fraction and total ozone column at noon as input from the ERA-40 data series (i.e. the 40 + year European Centre for Medium-Range Weather Forecasts Re-Analysis archive). By comparing the model results against high accuracy measurements at two different locations in Norway, we found the method for estimating the number of VD-hours to be accurate within 2.5 +/- 7% or better for moderate solar zenith angles (< 65 degrees). For higher solar zenith angles (> 65 degrees) the results are more variable, but the contribution to a population's vitamin D level from solar radiation when the sun is this low in the sky is rather small. The program code to compute VD-hours from ERA-40 files is written in Perl (v 5.8.7) and may be obtained free of charge by contacting corresponding author.

Ultraviolet exposure scenarios: risks of erythema from recommendations on cutaneous vitamin D synthesis.

Exposure to sunlight is a major source of vitamin D for most people yet public health advice focuses overwhelmingly on avoiding exposure of unprotected skin because of the risks of erythema and skin cancer. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that the current recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year and for all the year at some (low) latitudes. At the higher proposed vitamin D dose of 1000 IU lunchtime sun exposure is still a viable route to the vitamin, but requires the commitment to expose greater areas of skin, or is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.

The high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitude.

BACKGROUND: Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season. METHODS: We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27 degrees S; 167 females and 211 males), Geelong region (38 degrees S; 561 females), and Tasmania (43 degrees S; 432 females and 298 males). RESULTS: The prevalence of vitamin D insufficiency (

Calculated ultraviolet exposure levels for a healthy vitamin D status.

The dangers of overexposure to sunlight have been well publicized, but less attention has been given to an acknowledged benefit of exposure to UV radiation; that being the cutaneous synthesis of vitamin D3. Here we define a standard vitamin D dose on the basis of recently recommended requirements for vitamin D that take account of its risk reduction role in a variety of diseases, and present a web-based tool that enables the reader to calculate associated exposure times for any time and place using either default values or user-selected conditions. Either it is not possible to synthesize vitamin D3 at high latitudes in winter, or the exposure time required to reach a standard dose is sometimes impractical. Where solar UV is sufficient, a risk-benefit analysis of sunburn vs. vitamin D3 synthesis shows that the best time for brief sun exposure is in the middle of the day. For low solar elevation angles common at high latitudes, a fine line exists between adequate UV exposure for vitamin D3 synthesis and a risk of sun burn.

Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness.

Vitamin D production in human skin occurs only when incident UV radiation exceeds a certain threshold. From simulations of UV irradiances worldwide and throughout the year, we have studied the dependency of the extent and duration of cutaneous vitamin D production in terms of latitude, time, total ozone, clouds, aerosols, surface reflectivity and altitude. For clear atmospheric conditions, no cutaneous vitamin D production occurs at 51 degrees latitude and higher during some periods of the year. At 70 degrees latitude, vitamin D synthesis can be absent for 5 months. Clouds, aerosols and thick ozone events reduce the duration of vitamin D synthesis considerably, and can suppress vitamin D synthesis completely even at the equator. A web page allowing the computation of the duration of cutaneous vitamin D production worldwide throughout the year, for various atmospheric and surface conditions, is available on the Internet at http://zardoz.nilu.no/~olaeng/fastrt/VitD.html and http://zardoz.nilu.no/~olaeng/fastrt/VitD-ez.html. The computational methodology is outlined here.

The relationship between ultraviolet radiation exposure and vitamin D status.

This paper reviews the main factors influencing the synthesis of vitamin D, with particular focus on ultraviolet radiation exposure. On the global level, the main source of vitamin D is the sun. The effect of solar radiation on vitamin D synthesis depends to some extent on the initial vitamin D levels. At moderate to high latitudes, diet becomes an increasingly important source of vitamin D due to decreased solar intensity and cold temperatures, which discourage skin exposure. During the mid-winter season, these factors result in decreased solar radiation exposure, hindering extensively the synthesis of vitamin D in these populations.

Antineutrophil cytoplasmic antibody-associated vasculitides: could geographic patterns be explained by ambient ultraviolet radiation?

OBJECTIVE: This ecological study describes and quantifies the association between ambient ultraviolet (UV) radiation levels, including daily winter vitamin D effective UV radiation levels and the incidence of the 3 antineutrophil cytoplasmic antibody-associated vasculitides (AAVs): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS). Latitudinal variation in occurrence of the AAVs, especially WG, has been previously reported. For other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, inverse associations with latitude are hypothesized to indicate a causative role for low UV radiation exposure, possibly acting via vitamin D status. METHODS: Published epidemiologic studies provided data on incident cases, total population of study regions, age-specific incidence rates, and study location. From these data and online age-specific population data, we calculated crude incidence rates, the expected number of cases (to control for possible age confounding), and measures of ambient UV radiation. Negative binomial regression models were used to calculate the incidence rate ratio (IRR) for a 1,000 joules/m(2) increase in ambient UV radiation. RESULTS: The incidence of WG and CSS increased with increasing latitude and decreasing ambient UV radiation, with a stronger and more consistent effect across different UV radiation measures for WG, e.g., for average daily ambient clear sky erythemal UV radiation (WG: IRR 0.64 [95% confidence interval (95% CI) 0.44-0.94], P = 0.02; CSS: IRR 0.67 [95% CI 0.43-1.05], P = 0.08; MPA: IRR 1.16 [95% CI 0.92-1.47], P = 0.22). There was no apparent latitudinal variation in MPA incidence. CONCLUSION: Our findings are consistent with a protective immunomodulatory effect of ambient UV radiation on the onset of WG and CSS. We discuss possible mechanisms, including the effect of vitamin D on the immune system.

The solar UV radiation level needed for cutaneous production of vitamin D3 in the face. A study conducted among subjects living at a high latitude (68 degrees N).

Populations at high latitudes experience several winter months with insufficient UV solar radiation to induce a significant cutaneous production of vitamin D. This unique study was designed to pursue an in vivo threshold of UV radiation needed for cutaneous production of vitamin D to take place if only the face was exposed to UV radiation. The vitamin D status were measured by analyzing blood samples weekly from a study group of 15 subjects over a period of 2 months during late winter, when UV radiation can be expected to increase substantially from rising solar elevations. Statistical analysis showed no significant positive association between the mean UV radiation dose and the mean 25(OH)D (25-hydroxy vitamin D) for the group. On an individual basis, however, we found indications that subjects with very low initial concentration of 25(OH)D (<30 nmol l(-1)) seemed to respond to UV radiation as early as in the beginning of March. For other individuals diet seemed to be the dominant controlling factor for 25(OH)D levels.

Seasonality of UV-radiation and vitamin D status at 69 degrees north.

The main purpose with this study was to assess the seasonal variation in measured UV-radiation and its impact on vitamin D status throughout one year in subjects living at high latitude. Blood samples drawn from 60 volunteers (44 women, 16 men) living at Andenes (69 degrees N), Norway, were collected throughout one year, at two-month intervals. The blood samples were analysed for 25-hydroxy vitamin D [25(OH)D]. Data on dietary intakes of vitamin D, time spent in daylight, use of sun beds and sun seeking holidays were collected by using questionnaires. The ambient vitamin D effective UV-radiation was measured at a site near by Andenes, and the number of hours spent outdoors with sufficient radiation for cutaneous vitamin D production (UV-hours) was estimated for each day. The mean 25(OH)D values were significantly higher at the end of the summer and in December, 2004 and varied from 42.0 nmol L(-1) in October, 2004 and April, 2005 to around 47 nmol L(-1) in December, 2004 and September, 2005. For the whole group, a positive relationship between UV-hours and 25(OH)D was found at UV-hours>or=3.5. However, for subjects with lower 25(OH)D levels i.e. at least one blood measurement with 25(OH)D<37.5 nmol L(-1), the positive relationship were found at around 1.5 UV-hours and more, whereas for the group of subjects that had all their vitamin D values above 37.5 nmol L(-1), positive relationship was found at UV-hours>or=4.0, when adjusting for vitamin D intake, sun bed use and sun seeking holidays. The generally high dietary intakes of vitamin D, especially in winter, mask largely the effect of seasonal variation in UV-exposure, causing an atypical seasonal variation in vitamin D status. The UV-hour variable significantly predicted 25(OH)D levels in blood when adjusted for intakes and artificial UV-radiation exposure and sun holidays abroad.