The feasibility ofin vivoquantification of bone-fluorine in humans by delayed neutron activation analysis: a pilot study

Abstract

Fluorine (F) plays an important role in dental health and bone formation. Many studies have shown that excess fluoride (F(-)) can result in dental or skeletal fluorosis, while other studies have indicated that a proper dosage of fluoride may have a protective effect on bone fracture incidence. Fluorine is stored almost completely in the skeleton making bone an ideal site for measurement to assess long-term exposure. This paper outlines a feasibility study of a technique to measure bone-fluorine non-invasively in the human hand using in vivo neutron activation analysis (IVNAA) via the (19)F(n,γ)(20)F reaction. Irradiations were performed using the Tandetron accelerator at McMaster University. Eight NaI(Tl) detectors arranged in a 4π geometry were employed for delayed counting of the emitted 1.63 MeV gamma ray. The short 11 s half-life of (20)F presents a difficult and unique practical challenge in terms of patient irradiation and subsequent detection. We have employed two simultaneous timing methods to determine the fluorine sensitivity by eliminating the interference of the 1.64 MeV gamma ray from the (37)Cl(n,γ)(38)Cl reaction. The timing method consisted of three counting periods: an initial 30 s (sum of three 10 s periods) count period for F, followed by a 120 s decay period, and a subsequent 300 s count period to obtain information pertaining to Ca and Cl. The phantom minimum detectable limit (M(DL)) determined by this method was 0.96 mg F/g Ca. The M(DL) was improved by dividing the initial timing period into three equal segments (10 s each) and combining the results using inverse variance weighting. This resulted in a phantom M(DL) of 0.66 mg F/g Ca. These detection limits are comparable to ex vivo results for various bones in the adult skeleton reported in the literature. Dosimetry was performed for these irradiation conditions. The equivalent dose for each phantom measurement was determined to be 30 mSv. The effective dose was however low, 35 µSv, which is comparable to other clinical diagnostic tools. The M(DL), relatively low radiation dose and non-invasiveness indicate the suitability of this method for routine in vivo analysis of bone-fluorine content. This prompted us to perform a trial study in human subjects. A preliminary human study on 34 participants was completed, with 33 of the 34 measurements proving to be successful. The in vivo M(DL) based on the improved timing method was determined to be 0.69 mg F/g Ca for the 33 successful human measurements. In our opinion, this technique has been demonstrated to be a suitable method for in vivo assessment of fluorine bone-burden.

Correlation between fluorine content in tea and bone assessed using neutron activation analysis in a Canadian urban population

“…We previously showed that bone fluorine content increases linearly with age (p \ 0.001) [13,18]. Fluorine was found to increase at a rate of 0.08 ± 0.01 mg F/g Ca per year.…”

“…We employ the 19 F(n,c) 20 F reaction [13] which has a 9.6 mb cross-section. 20 F has an 11.2 s half life so irradiation of the person, transfer to a detector, and the detection of c-rays must all be performed quickly [14].…”

“…At McMaster University, we have developed a system to measure fluorine in bone non-invasively in vivo to allow us to assess directly fluorine levels in an individual's organ at risk [13] and thus allow more precise measurements of fluorine exposure, uptake and retention. This paper presents data from our neutron activation analysis-based technique for the measurement of in vivo bone fluorine content showing a relationship between bone fluorine content and tea drinking.…”

An investigation of the neutron flux in bone-fluorine phantoms comparing accelerator based in vivo neutron activation analysis and FLUKA simulation data

“…We have previously shown that neutron activation analysis (NAA) is a useful technique for the in vivo measurement of fluorine [12,11]. We developed a system, which measures the delayed gamma rays emitted following the decay of 20 F. This isotope is produced via the neutron capture reaction 19 F(n,c) 20 F. The system is being developed to study people who are commonly exposed to fluorine.…”

“…This work followed on from earlier studies, which showed that we could detect fluoride in the bone in the majority of adult urban Canadians in a small pilot study of volunteers. We could measure fluoride with 95% confidence in 33 out of 34 volunteers [11,12]). We employ a system, which uses the McMaster University Tandetron accelerator to irradiate both calibration phantoms and human hands.…”