Multicenter Evaluation of Frequency and Impact of Activity Infiltration in PET Imaging, Including Microscale Modeling of Skin-Absorbed Dose.

There has been significant recent interest in understanding both the frequency of nuclear medicine injection infiltration and the potential for negative impact, including skin injury. However, no large-scale study has yet correlated visualized injection site activity with actual activity measurement of an infiltrate. Additionally, current skin dosimetry approaches lack sufficient detail to account for critical factors that impact the dose to the radiosensitive epidermis. Methods: From 10 imaging sites, 1,000 PET/CT patient studies were retrospectively collected. At each site, consecutive patients with the injection site in the field of view were used. The radiopharmaceutical, injected activity, time of injection and imaging, injection site, and injection method were recorded. Net injection site activity was calculated from volumes of interest. Monte Carlo image-based absorbed dose calculations were performed using the actual geometry from a patient with a minor infiltration. The simulation model used an activity distribution in the skin microanatomy based on known properties of subcutaneous fat, dermis, and epidermis. Simulations using several subcutaneous fat-to-dermis concentration ratios were performed. Absorbed dose to the epidermis, dermis, and fat were calculated along with relative γ- and ß-contributions, and these findings were extrapolated to a hypothetical worst-case (470 MBq) full-injection infiltration. Results: Only 6 of 1,000 patients had activity at the injection site in excess of 370 kBq (10 µCi), with no activities greater than 1.7 MBq (45 µCi). In 460 of 1,000 patients, activity at the injection site was clearly visualized. However, quantitative assessment of activities averaged only 34 kBq (0.9 µCi), representing 0.008% of the injected activity. Calculations for the extrapolated 470-MBq infiltration resulted in a hypothetical absorbed dose to the epidermis of below 1 Gy, a factor of 2 lower than what is required for deterministic skin reactions. Analysis of the dose distribution demonstrates that the dermis acts as a ß-shield for the radiation-sensitive epidermis. Dermal shielding is highly effective for low-energy 18F positrons but less so with the higher-energy positrons of 68Ga. Conclusion: When quantitative activity measurement criteria are used rather than visual, the frequency of PET infiltration appears substantially below frequencies previously published. Shallow doses to the epidermis from infiltration events are also likely substantially lower than previously reported because of absorption of ß-particles in the dermis.

Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration.

To illustrate the use of imaging to quantify the transfer of materials from the nasal cavity to other anatomical compartments, specifically, transfer to the brain using the thymidine analogue, [18F]fluorothymidine (FLT), and the glucose analogue, [18F]fluorodeoxyglucose (FDG). Anesthetized rats were administered FLT or FDG by intranasal instillation (IN) or tail-vein injection (IV). PET/CT imaging was performed for up to 60 min. Volumes-of-interest (VOIs) for the olfactory bulb (OB) and the remaining brain were created on the CT and transferred to the co-registered dynamic PET. Time-activity curves (TACs) were generated and compared. The disposition patterns were successfully visualized and quantified and differences in brain distribution patterns were observed. For FDG, the concentration was substantially higher in the OB than the brain only after IN administration. For FLT, the concentration was higher in the OB than the brain after both IN and IV and higher after IN than after IV administration at all times, whereas the concentration in the brain was higher after IN than after IV administration at early times only. Approximately 50 and 9% of the IN FDG and FLT doses, respectively, remained in the nasal cavity at 20 min post-administration. The initial phase of clearance was similar for both agents (t1/2 = 2.53 and 3.36 min) but the slow clearance phase was more rapid for FLT than FDG (t1/2 = 32.1 and 85.2 min, respectively). Pharmacoimaging techniques employing PET/CT can be successfully implemented to quantitatively investigate and compare the disposition of radiolabeled agents administered by a variety of routes.

Demonstration of Nucleoside Transporter Activity in the Nose-to-Brain Distribution of [18F]Fluorothymidine Using PET Imaging.

To evaluate the role of nucleoside transporters in the nose-to-brain uptake of [18F]fluorothymidine (FLT), an equilibrative nucleoside transporter (ENT1,2) and concentrative nucleoside transporter (CNT1-3) substrate, using PET to measure local tissue concentrations. Anesthetized Sprague-Dawley rats were administered FLT by intranasal (IN) instillation or tail-vein injection (IV). NBMPR (nitrobenzylmercaptopurine riboside), an ENT1 inhibitor, was administered either IN or intraperitoneally (IP). Dynamic PET imaging was performed for up to 40 min. A CT was obtained for anatomical co-registration and attenuation correction. Time-activity curves (TACs) were generated for the olfactory bulb (OB) and remaining brain, and the area-under-the-curve (AUC) for each TAC was calculated to determine the total tissue exposure of FLT. FLT concentrations were higher in the OB than in the rest of the brain following IN administration. IP administration of NBMPR resulted in increased OB and brain FLT exposure following both IN and IV administration, suggesting that NBMPR decreases the clearance rate of FLT from the brain. When FLT and NBMPR were co-administered IN, there was a decrease in the OB AUC while an increase in the brain AUC was observed. The decrease in OB exposure was likely the result of inhibition of ENT1 uptake activity in the nose-to-brain transport pathway. FLT distribution patterns show that nucleoside transporters, including ENT1, play a key role in the distribution of transporter substrates between the nasal cavity and the brain via the OB.

Factors influencing health care-seeking behaviours among Mayan women in Guatemala.

OBJECTIVE: to identify and better understand factors that influence care-seeking behaviour for women's health among indigenous Mayan populations in the highlands of Guatemala. DESIGN: adaptation of qualitative anthropological methods involving observations, key informant interviews and focus group discussions (FGDs). SETTING: Project Concern International's Casa Materna, Huehuetenango, Guatemala. PARTICIPANTS: Interviews and FGDs were conducted among 21 clients (current or past) of the Casa Materna and traditional birth attendants; 17 female advocates/promoters of the Casa Materna and related services; and 12 male advocates, including spouses, non-government organisation staff and community health workers. FINDINGS: the following findings emerged from focus group data: Women's support groups (WSGs) provided an enabling environment in which women could form friendships, bond, discuss concerns about their reproductive health, and identify concrete ways of addressing them; Supportive friends, family members and advocates influenced women's decisions to seek health care at the Casa Materna; Women's decisions to seek care were often associated with their sense of self-worth and self-esteem, and women's self-esteem was enhanced by their participation in the WSGs; Women's decisions to seek care were influenced by the perception that women would be able to access culturally appropriate, safe and secure health care services at the Casa Materna; The learned behaviour of negotiation with key decision-makers and/or opinion leaders was an effective tool for convincing such individuals of the value of accessing facility-based care; The proven track record, high quality of services and cultural competence offered at the Casa Materna increased the confidence and level of trust of clients and their family members about the care that would be received; Couple-based education and health promotion were effective techniques for achieving behaviour and attitude change among both men and women. KEY CONCLUSIONS: the Casa Materna and its community outreach strategy serve an essential purpose in the provision of maternity care for the isolated and vulnerable families of the Guatemalan highlands, by bridging traditional and Western approaches to health care services. The Casa Materna service model plays a critical role in improving women's self-efficacy and ultimately strengthening the social fabric that characterises this high risk and vulnerable population. IMPLICATIONS FOR PRACTICE: the Casa Materna model provides a foundation upon which to bridge and strengthen the relationship between community advocates, traditional community-based health care providers, and the government-funded system of health care. The findings of this study should be incorporated into future research to determine the potential for bringing the model to scale.