Natalie Charnley

Optimization of the Injected Activity in Dynamic 3D PET: A Generalized Approach Using Patient-Specific NECs as Demonstrated by a Series of 15O-H2O Scans

The magnitude of the injected activity (A0) has a direct impact on the statistical quality of PET images. This study aimed to develop a generalized method for maximizing the statistical quality of dynamic PET images by optimizing A0. Methods: Patient-specific noise-equivalent counts (PS-NECs) were used as a metric of the statistical quality of each time frame of a dynamic PET image. Previous methodology developed to extrapolate the NEC as a function of A0 was extended to dynamic PET, enabling the NEC to be extrapolated as a function of both A0 and the time after injection. This method allowed A0 to be optimized after a single scan (at a single A0), by maximizing the NEC within the time interval for which the parameter estimation is most sensitive. The extrapolation method was validated by a series of 15O-H2O scans of the body acquired in 3-dimensional mode. Each patient (n = 6) underwent between 3 and 6 scans at 1 bed position. The injected activities were varied over a wide range (140–840 MBq). Noise-equivalent counting rate (NECR) versus A0 curves and the optimal injected activities were calculated from each injection. Results: PS-NECR versus A0 curves as extrapolated from different injected activities were consistent (coefficient of variation, typically <5%). The optimal injected activities for an individual, as derived from these curves, were also consistent (maximum coefficient of variation, 4.3%). For abdominal (n = 4) and chest (n = 1) scans, we found optimal injected activities of 15O-H2O in the range of 220–350 MBq for estimating blood perfusion (F) and 660–1,070 MBq for estimating the volume of distribution (VT). Higher optimal injected activities were found in the case of a pelvic scan (n = 1; 570 MBq for F and 1,530 MBq for VT). Conclusion: PS-NECs are a valid and generic method for optimizing the injected activity in PET, allowing scanning protocols to be improved after the collection of an initial, single dynamic dataset. This generic method can be used to estimate the optimal injected activity, which is specific to the patient, tracer, PET scanner, and body region being scanned.

Development and validation of a variance model for dynamic PET: uses in fitting kinetic data and optimizing the injected activity.

The precision of biological parameter estimates derived from dynamic PET data can be limited by the number of acquired coincidence events (prompts and randoms). These numbers are affected by the injected activity (A(0)). The benefits of optimizing A(0) were assessed using a new model of data variance which is formulated as a function of A(0). Seven cancer patients underwent dynamic [(15)O]H(2)O PET scans (32 scans) using a Biograph PET-CT scanner (Siemens), with A(0) varied (142-839 MBq). These data were combined with simulations to (1) determine the accuracy of the new variance model, (2) estimate the improvements in parameter estimate precision gained by optimizing A(0), and (3) examine changes in precision for different size regions of interest (ROIs). The new variance model provided a good estimate of the relative variance in dynamic PET data across a wide range of A(0)s and time frames for FBP reconstruction. Patient data showed that relative changes in estimate precision with A(0) were in reasonable agreement with the changes predicted by the model: Pearsons correlation coefficients were 0.73 and 0.62 for perfusion (F) and the volume of distribution (V(T)), respectively. The between-scan variability in the parameter estimates agreed with the estimated precision for small ROIs (<5 mL). An A(0) of 500-700 MBq was near optimal for estimating F and V(T) from abdominal [(15)O]H(2)O scans on this scanner. This optimization improved the precision of parameter estimates for small ROIs (<5 mL), with an injection of 600 MBq reducing the standard error on F by a factor of 1.13 as compared to the injection of 250 MBq, but by the more modest factor of 1.03 as compared to A(0) = 400 MBq.

Principles of PET in Cancer Treatment for the Assessment of Chemotherapy and Radiotherapy Response and for Radiotherapy Treatment Planning

Inclusion of PET images to guide radiotherapy planning has advantages. Definition of target volumes of areas equivocal for malignancy can be done with greater certainty, but depends on sensitivity and specificity at that site. There is a huge potential for biologic dose planning using intensity-modulated radiation therapy (IMRT), which will expand with the development of new tracers. However, only one published study demonstrates a survival benefit from incorporating PET into treatment planning. Further clinical studies and outcome analysis are required to evaluate cost effectiveness and overall utility before a change in practice can be recommended. For current radiotherapy treatment planning, PET images are best used as a guide alongside CT images and should be done so with caution.

Assessment of Drug Resistance in Anticancer Therapy by Nuclear Imaging

The ability to assess and monitor resistance to drugs in situ has potential to provide an image-guided means of individualising cancer chemotherapy. Molecular imaging of factors associated with drug resistance could be used to prevent the use of ineffective treatments and eliminate the need to wait for conventional measures showing lack of response. Molecular imaging also has the potential to increase understanding of mechanisms underlying drug resistance in vivo in man, which should aid the development of approaches for increasing the effectiveness of cancer treatment. Resistance may be due to several processes including pharmacokinetics, metabolism, physiology and molecular biology, all of which can be assessed by molecular imaging.

Maximizing model parameter precision by optimizing dose in 3D [ 15 O]H 2 O PET scans

Dynamic PET imaging with [15O]H2O allows estimation of tumour perfusion in humans. For small regions of interest these estimates have limited precision due to statistical noise in the images. We have optimized the injected dose in order to improve the precision of these estimates. This optimization considers the effect of the scanner count-rate upon the local image variance and the subsequent effect on the parameter estimation. The work includes examination of variance images reconstructed via Alpert’s method and Monte Carlo simulations of the kinetic modelling process. Optimal doses are derived from [15O]H2O PET studies performed on a modern whole-body 3D PET/CT scanner (n=7). These scans (mostly abdominal) show that changes in local image variance can be predicted by the global count-rates to within 15 % over a wide range of injected doses and for the majority of the time-course of the dynamic scan. We find optimal doses for estimation of perfusion (F) in the range of 250-530 MBq, and 520-730 MBq for estimation of the volume of distribution (VT). Injection at 100-200 MBq greater than the calculated optimum rarely degrades the precision of the parameter estimates. Hence, a standardized dose of 500-700 MBq would be appropriate for these subjects if estimating F and VT simultaneously.

Testing a prognostic model in patients with metastatic castrate resistant prostate cancer (MCRPC) treated prechemotherapy with abiraterone.

283 Background: There is a need for prognostic models in metastatic prostate cancer to determine optimal treatment pathways on development of castrate resistance. Abiraterone is an androgen biosynthesis inhibitor. Efficacy was proven in patients with MCRPC prechemotherapy in the COU-AA-302 trial with PSA PFS 11.1 months (Raj et al New Eng J med 2013). We have previously investigated prognostic factors in MCRPC (Charnley et al J Clin Oncol 2014). We reported a prognostic model which predicts that if alk phos rise ≥100 in the preceding 3 months and/or Hb<11 there is no response. The model was correct in 78.9% of responders and 55% of non responders (overall 66.7%). We test the model in an independent group of 81 patients prechemotherapy, some from a different treating centre. Methods: 81 patients with metastatic CRPC received abiraterone 1g daily prechemotherapy. Response to abiraterone was defined as a 50% reduction in PSA. Alk phos rise ≥100 in the previous 3 months and Hb<11 were related to PSA response....