The British nuclear medicine research strategy - the framework.

The British Nuclear Medicine Society (BNMS) has developed a Research Strategy framework led by the Research Champions of the BNMS and overseen by the BNMS Research and Innovation Committee. The objectives of the Research Strategy are to improve translation of cutting-edge nuclear medicine research from bench to bedside, the implementation of state-of-the-art multimodality technologies and to enhance multicentre radionuclide research in the UK. It strives to involve patients and the public in radionuclide research and to contribute to and work with the multi-professional national and international organisations involved in research with an ultimate aim to improve nuclear medicine services, and patients' outcomes and care.

Bone lesion absorbed dose profiles in patients with metastatic prostate cancer treated with molecular radiotherapy.

OBJECTIVE: The aim of this study was to calculate the range of absorbed doses that could potentially be delivered by a variety of radiopharmaceuticals and typical fixed administered activities used for bone pain palliation in a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). The methodology for the extrapolation of the biodistribution, pharmacokinetics and absorbed doses from a given to an alternative radiopharmaceutical is presented. METHODS: Sequential single photon emission CT images from 22 patients treated with 5 GBq of 186Re-HEDP were used to extrapolate the time-activity curves for various radiopharmaceuticals. Cumulated activity distributions for the delivered and extrapolated treatment plans were converted into absorbed dose distributions using the convolution dosimetry method. The lesion absorbed doses obtained for the different treatments were compared using the patient population distributions and cumulative dose-volume histograms. RESULTS: The median lesion absorbed doses across the patient cohort ranged from 2.7 Gy (range: 0.6-11.8 Gy) for 1100 MBq of 166Ho-DOTMP to 21.8 Gy (range: 4.5-117.6 Gy) for 150 MBq of 89Sr-dichloride. 32P-Na3PO4, 153Sm-EDTMP, 166Ho-DOTMP, 177Lu-EDTMP and 188Re-HEDP would have delivered 41, 32, 85, 20 and 64% lower absorbed doses, for the typical administered activities as compared to 186Re-HEDP, respectively, whilst 89Sr-dichloride would have delivered 25% higher absorbed doses. CONCLUSION: For the patient cohort studied, a wide range of absorbed doses would have been delivered for typical administration protocols in mCRPC. The methodology presented has potential use for emerging theragnostic agents. Advances in knowledge: The same patient cohort can receive a range of lesion absorbed doses from typical molecular radiotherapy treatments for patients with metastatic prostate cancer, highlighting the need to establish absorbed dose response relationships and to treat patients according to absorbed dose instead of using fixed administered activities.

Phase I/II trials of 186Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival.

PURPOSE: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. METHODS: Clinical data from 57 patients who received 2.5-5.1 GBq of 186Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan-Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses. RESULTS: A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10-0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of 186Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004). CONCLUSION: This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose-response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry.

Early gated SPECT adenosine myocardial perfusion imaging may influence the therapeutic management of patients with coronary artery disease.

AIM: The aim of the study was to investigate whether myocardial perfusion imaging at 15 min after injection (T15) is more accurate in detecting coronary artery disease than that at 45 min (T45). PATIENTS AND METHODS: Two-day stress/rest 99mTc-tetrofosmin gated SPECT was performed at T15 and T45 in 50 patients. Coronary angiography was considered when poststress and resting images were discordant. Tracer washout rates were calculated for the myocardium, liver, and subdiaphragmatic region. Perfusion sum difference scores were derived using QPS software. RESULTS: T15 and T45 were discordant in 18/50 (36%) patients. In 16/18 patients (89%) discordant deficits were more apparent at T15. A total of 13/16 patients underwent coronary angiography, of whom 12 had coronary artery disease. Poststress, but not resting, left ventricular ejection fraction was lower at T15 (P=0.02). Sum difference scores were higher at T15 [2.2 (1.9)] than at T45 [1.6 (1.7); P<0.05]. Tracer washout rates from the liver [46 (13.3)%] and subdiaphragmatic region [36 (21.3)%] were significant (P<0.0001), but there was no change in myocardial activity. CONCLUSION: T15 detected more abnormalities than did T45. The reduction in left ventricular ejection fraction after stress may result from adenosine-induced poststunning at T15. Accordingly, the T15 protocol may be useful in the assessment of hibernating myocardium. Contrasting myocardial and hepatic washout rates may be attributable to differential ABC transporter expression.

The potential use of 99mTc-MDP bone scans to plan high-activity 186Re-HEDP targeted therapy of bony metastases from prostate cancer.

Patients with skeletal metastases from hormone-refractory prostate cancer have shown variable responses to high-activity therapy with (186)Re-HEDP and peripheral stem cell support. In this paper, we report on the use of a novel technique to compare sequential planar images acquired post-(186)Re-HEDP therapy administration with pretherapy diagnostic (99m)Tc-MDP scans, to evaluate the turnover of the radiopharmaceutical in normal and abnormal bone. It was found that the activity in normal (i.e., disease-free) segments of the spine demonstrates a faster effective decay than that of the metastases, with the latter showing only physical decay. This study showed, for the first time, a detailed correlation in the behavior of the (99m)Tc-MDP and (186)Re-HEDP images, encouraging the possibility of using the pretherapy 99mTc-MDP scan for estimations of absorbed doses to be delivered by prescribed activities of (186)Re-HEDP.

Complementary alternative medicine and nuclear medicine.

Complementary alternative medicines (CAMs), including food supplements, are taken widely by patients, especially those with cancer. Others take CAMs hoping to improve fitness or prevent disease. Physicians (and patients) may not be aware of the potential side-effects and interactions of CAMs with conventional treatment. Likewise, their known physiological effects could interfere with radiopharmaceutical kinetics, producing abnormal treatment responses and diagnostic results. Nuclear medicine physicians are encouraged to question patients on their intake of CAMs when taking their history prior to radionuclide therapy or diagnosis. The potential effect of CAMs should be considered when unexpected therapeutic or diagnostic results are found.