Introduction

The concept of image quality is a generic one that applies to all types of images but remains subjective (₁). In Nuclear Medicine, image quality may translate, either directly or indirectly, to diagnostic integrity. The quality of bone scintigraphy has been shown to have many variables, including the radiopharmaceutical (₂,₃), patient age (₄), patient gender (₂), the interval between injection and scan time (₅), and radiopharmaceutical incubation period (₆). Radiochemical purity, or the percentage of successfully, is another important factor in bone scan quality (₇,₈). Radiochemical impurities are detrimental to image quality as the impurity has different biodistribution in the body from that of normal labelled radiopharmaceutical; contributing to a poorer target to background ratio (₇,₈).

Both Technetium-99m (99mTc) and Technetium-99 (99Tc) are daughter products of the parent molybdenum-99 (99Mo), however, 99Tc is also the daughter of 99mTc (₇,₉). 99Tc, with a very long half-life of 2.1 x 105 years, decays to stable ruthenium-99 with the emission of a beta particle (₇,₉). Chemically, 99mTc and 99Tc are identical and are the same isotope by definition; although different nuclides (₇). During radiopharmaceutical reconstitution, they both compete for the same binding sites (₇). In sufficient numbers, 99Tc atoms could result in some of the 99mTc atoms remaining unbound after bone radiopharmaceutical reconstitution, producing free 99mTc pertechnetate (₇). Bone imaging agents accumulate in bone regardless of whether it is bound to 99mTc or 99Tc, however, 99Tc will remain undetected during bone scintigraphy.

Given the short half life of 99mTc (6.02 hours), the very long half life of 99Tc and the decay of both 99Mo and 99mTc to 99Tc, the proportion of 99Tc on the radionuclide generator column will increase over time (₇,₉). At 3 hours post elution, 99mTc represents 72.7% of the total technetium atoms on the column. This decreases to 27.7% by 24 hours post elution (typical elution period) and just 7.7% at 72 hours (typical Monday ingrowth in the absence of out of hours work) (₇).

Research Question

Anecdotally, a number of unusual bone radiopharmaceutical biodistributions have been noted following long weekends. In these cases, the generator ingrowth time was a minimum of 96 hours and possibly as much as 144 hours. The fraction of 99Tc atoms in the eluate would be well in excess of that of 99mTc (less than 5% 99mTc). It was hypothesised that the extended generator ingrowth provided sufficiently high concentrations of 99Tc in the competitive pool to displace 99mTc from binding sites and degrade bone scan quality. The aim of this study was to determine what impact a long generator ingrowth time has on image quality.

Methodology

The investigation was a prospective analysis of consecutive patients presenting for routine bone imaging to a single Nuclear Medicine department on Mondays and Tuesdays over a period of six weeks. The patients were scanned as per department protocol and referral. Patients were randomly allocated to scan day, injection time and scan time. 99mTc labelled MDP (Radpharm Scientific, Canberra) was employed for all patients. The 99mTc MDP was prepared according to manufacturer specifications using 99mTc eluate of a 99Mo/99mTc 80 GBq Gentech generator (ARI, Sydney).

Patient age, gender, and time between injection and scanning were recorded. Bone scan images were then examined subjectively for evidence of thyroid accumulation (free pertechnetate) or any other unusual biodistribution. Two simple ROIs with total count rates determination were used to calculate bone to soft tissue ratios. The ROIs were of the same size and ROIs excluded any areas of pathology. Where possible, a femur to thigh ratio was performed, however, spine to adjacent non-renal soft tissue, humerus to arm, or tibia to calf ratios were calculated in some patients.

This research approved by the Ethics in Human Research Committee of the School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, Australia.

Results

The study population included 92 patients. One patient was excluded on the basis of widespread metastatic disease, two patients were excluded due to poor skeletal uptake and four patients were excluded due to out of hours generator elution. All remaining 85 patients had either a normal bone scan or findings that did not interfere with the evaluation of images. Seventy three patients had femur/thigh ratios calculated, six patients had humerus/arm ratios calculated, five had tibia/calf ratios calculated, and one had a spine/adjacent non-renal soft tissue ratio calculated. No statistically significant difference was noted between the Monday and Tuesday cohorts for age (P = 0.634), gender (P = 0.827) or injection to scan time (P = 0.386) (table 1).

Figure 1

Table 1: Distribution of patients in the two groups according to age and gender, and the average injection to scan time.

The mean target to background ratio of the Monday group was 2.28 (95% CI = 2.10 to 2.47). The mean target to background ratio of the Tuesday group was 2.39 (95% CI = 2.24 to 2.54). The overlap of the 95% CI supports the students t-test in suggesting no statistically significant difference between the two groups (P = 0.390).

In an effort to better control variables known to influence bone scan quality, patients were excluded if they were younger than 20 years, if a femur : thigh ratio was not calculated, if the injection to scan time was outside the 2.5 hours to 3.5 hours window. No statistically significant difference was noted between the Monday and Tuesday cohorts for age (P = 0.898), gender (P = 0.916) or injection to scan time (P = 0.667) (table 2). The mean target to background ratio of the Monday group was 2.15 (95% CI = 1.98 to 2.33). The mean target to background ratio of the Tuesday group was 2.30 (95% CI = 2.15 to 2.44). The overlap of the 95% CI supports the students t-test in suggesting there was still no statistically significant difference between the two groups (P = 0.213).

Figure 2

Table 2: Distribution of patients in the two groups according to age and gender, and the average injection to scan time.

Discussion/Conclusion

While the difference in the bone to soft tissue ratios at 24 and 72 hours post previous elution was not deemed to be statistically significant, the results show that the Tuesday patient group had a higher bone to soft tissue ratio. This raises the possibility that generator ingrowth time may affect bone scan image quality. Many clinical centres do not routinely elute their generators over standard weekends, resulting in a generator ingrowth time of 72 hours if the generator is eluted on a Friday and then Monday.

Generator ingrowth times greater than 72 hours may result in statistically significant differences being observed, and a more obvious degradation in bone scan image quality. This is especially important over a long weekend, particularly the four day Easter weekend. A limitation of this study was that any extravasation of the radiopharmaceutical at the injection site was not ascertained. Obviously a large extravasation could impact on bone to soft tissue ratio. This study was limited in the size of the patient population; a larger study population would provide a more definitive indication of whether generator ingrowth time effects bone scan image quality. Thus, further investigation is warranted to include a larger, multi-centre investigation that captures the Easter long weekend and which incorporates chromatography quality control of reconstituted radiopharmaceuticals.

Acknowledgements

Correspondence to

Geoff Currie School of Dentistry and Health Sciences Locked Bag 588 Charles Sturt University Wagga Wagga 2678 Australia Telephone: 61 2 69332822 Facsimile: 61 2 69332587 Email: gcurrie@csu.edu.au