The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.

Purpose: Pertuzumab, a first-in-class human epidermal receptor 2 (HER2) dimerization inhibitor, is a humanized monoclonal anti-HER2 antibody that binds HER2's dimerization domain and inhibits HER2 signaling. Based on supporting preclinical studies, we undertook a Phase II trial of pertuzumab in patients with recurrent non^small cell lung cancer (NSCLC). Experimental Design: Patients with previously treated NSCLC accessible for core biopsy and naive to HER pathway inhibitors were treated with pertuzumab i.v. once every 3 weeks. Tumor assessments were done at 6 and 12 weeks and then every 3 months thereafter. The primary efficacy end point was overall response rate by Response Evaluation Criteria in Solid Tumors. Measurement of tumor glucose metabolism (SUV max ) by F-18-fluorodeoxyglucose positron emission tomography was used as an exploratory pharmacodynamic marker of drug activity. Results: Of 43 patients treated with pertuzumab, no responses were seen; 18 of 43 (41.9%) and 9 of 43 (20.9%) patients had stable disease at 6 and 12 weeks, respectively. The median and 3-month progression-free survival rates (PFS) were 6.1 weeks (95% confidence interval, 5.3-11.3 weeks) and 28.4% (95% confidence interval, 14.4-44.2%), respectively. Of 22 patients who underwent F-18-fluorodeoxyglucose positron emission tomography, six (27.3%) had a metabolic response to pertuzumab as evidenced by decreased SUV max . These patients had prolonged PFS (HR = 0.11, log-rank P value = 0.018) compared with the 16 patients who had no metabolic response. Four patients (9.3%) experienced a grade 3/grade 4 adverse event judged related to pertuzumab; none exhibited grade 3/grade 4 cardiac toxicity. Conclusions: Pertuzumab is well tolerated as monotherapy. Pharmacodynamic activity correlated with prolonged PFS was detected in a moderate percentage of patients (27.3%). Further clinical development of pertuzumab should focus on rational combinations of pertuzumab with other drugs active in NSCLC.

We investigated the correlation between metabolic response by 18F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. Methods 18F-FDG PET was performed at baseline, 1–7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective response was defined by version 1.0 of the Response Evaluation Criteria in Solid Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by immunohistochemistry were done on tissue obtained at baseline or surgery. Results 18F-FDG PET showed high baseline tumor glycolytic activity (mean SUVmax, 14.2; range, 1.3–53.2), decreasing after 1 wk of imatinib mesylate (mean, 5.5; range, −0.5–47.7, P < 0.001, n = 44), and again before surgery (mean, 3.0; range, −0.5–36.1, P < 0.001, n = 40). At week 1, there were 3 patients with complete metabolic response (CMR), 33 with partial metabolic response (PMR), 6 with stable metabolic disease (SMD), and 2 with progressive metabolic disease (PMD). Before surgery, there were 3 with CMR, 33 with PMR, 4 with SMD, and none with PMD. The best response according to RECIST was 2 with partial response, 36 with stable disease, and 1 with progressive disease (n = 39). Of the patients with a posttreatment decrease in GLUT4 expression, 1 had CMR, 15 had PMR, 2 had SMD, and 1 had PMD at week 1, whereas before surgery 1 patient had CMR, 16 had PMR, 2 had SMD, and none had PMD. Among 27 patients with KIT exon 11 mutations, 1 had CMR, 22 had PMR, 3 had SMD, and 1 had PMD at week 1, whereas 1 had CMR, 22 had PMR, 2 had SMD, and 2 were unknown before surgery; among 4 patients with a wild-type genotype, 2 had PMR and 2 SMD at week 1, whereas 1 had CMR, 2 had PMR, and 1 had SMD before surgery. Conclusion After imatinib mesylate initiation, metabolic response by 18F-FDG PET was documented earlier (1–7 d) and was of much greater magnitude (36/44) than that documented by RECIST (2/39). Immunohistochemistry data suggest that GLUT4 may play a role in 18F-FDG uptake in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate therapy in most patients with PMR, and the biologic action of imatinib mesylate interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic response was observed as early as days 1–7 in patients with exon 11 mutations.

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Quantitative parameters such as the maximum and total counts in a volume are influenced by the partial volume effect. The magnitude of this effect varies with the non-stationary and anisotropic spatial resolution in SPECT slices. The objective of this investigation was to determine whether iterative reconstruction which includes modelling of the three-dimensional (3D) spatial resolution of SPECT imaging can reduce the impact of the partial volume effect on the quantitation of activity compared with filtered backprojection (FBP) techniques which include low-pass, and linear restoration filtering using the frequency distance relationship (FDR). The iterative reconstruction algorithms investigated were maximum-likelihood expectation-maximization (MLEM), MLEM with ordered subset acceleration (ML-OS), and MLEM with acceleration by the rescaled-block-iterative technique (ML-RBI). The SIMIND Monte Carlo code was used to simulate small hot spherical objects in an elliptical cylinder with and without uniform background activity as imaged by a low-energy ultra-high-resolution (LEUHR) collimator. Centre count ratios (CCRs) and total count ratios (TCRs) were determined as the observed counts over true counts. CCRs were unstable while TCRs had a bias of approximately 10% for all iterative techniques. The variance in the TCRs for ML-OS and ML-RBI was clearly elevated over that of MLEM, with ML-RBI having the smaller elevation. TCRs obtained with FDR-Wiener filtering had a larger bias (approximately 30%) than any of the iterative reconstruction methods but near stationarity is also reached. Butterworth filtered results varied by 9.7% from the centre to the edge. The addition of background has an influence on the convergence rate and noise properties of iterative techniques.