Background We conducted a phase I study with a granulocyte macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, ONCOS-102, in patients with solid tumors refractory to available treatments. The objectives of the study were to determine the optimal dose for further use and to assess the safety, tolerability and adverse event (AE) profile of ONCOS-102. Further, the response rate and overall survival were evaluated as well as preliminary evidence of disease control. As an exploratory endpoint, the effect of ONCOS 102 on biological correlates was examined. Methods The study was conducted using a classic 3 + 3 dose escalation study design involving 12 patients. Patients were repeatedly treated intratumorally with ONCOS-102 plus daily low-dose oral cyclophosphamide (CPO). Tumor response was evaluated with diagnostic positron emission tomography (PET) and computed tomography (CT). Tumor biopsies were collected at baseline and after treatment initiation for analysis of immunological correlates. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and during the study to assess antigen specificity of CD8+ T cells by interferon gamma (IFNγ) enzyme linked immunospot assay (ELISPOT). Results No dose limiting toxicity (DLT) or maximum tolerated dose (MTD) was identified for ONCOS-102. Four out of ten (40 %) evaluable patients had disease control based on PET/CT scan at 3 months and median overall survival was 9.3 months. A short-term increase in systemic pro-inflammatory cytokines and a prominent infiltration of TILs to tumors was seen post-treatment in 11 out of 12 patients. Two patients showed marked infiltration of CD8+ T cells to tumors and concomitant systemic induction of tumor-specific CD8+ T cells. Interestingly, high expression levels of genes associated with activated T_H1 cells and T_H1 type immune profile were observed in the post-treatment biopsies of these two patients. Conclusions ONCOS-102 is safe and well tolerated at the tested doses. All three examined doses may be used in further development. There was evidence of antitumor immunity and signals of clinical efficacy. Importantly, treatment resulted in infiltration of CD8+ T cells to tumors and up-regulation of PD-L1, highlighting the potential of ONCOS-102 as an immunosensitizing agent for combinatory therapies with checkpoint inhibitors. Trial registration NCT01598129. Registered 19/04/2012

Background.In this retrospective analysis we assessed the role of [¹⁸F]-FACBC-PET/CT in the prostatic cancer staging.Procedure.30 first [¹⁸F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging.Results.On 16 [¹⁸F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [¹⁸F]-FACBC findings was 9.5 ± 16.9 μg/L (0.54–69 μg/L) and in patients with negative [¹⁸F]-FACBC findings was 1.96 ± 1.87 μg/L (0.11–5.9 μg/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3–6 months) versus 31.2 ± 22.02 months (8–84 months),P<0.0001. There was a strong positive correlation between PSA value and number of metabolically active lesions (R=0.74) and a negative correlation between PDT and number of metabolically active lesions (R=-0.56). There was a weak negative correlation between PDT andSUVmax⁡(R=-0.30).Conclusion.According to our preliminary clinical experience, [¹⁸F]-FACBC-PET may play a role inin vivorestaging of an active prostate cancer, especially in patients with a short S-PSA doubling time.

The purpose of this study was to evaluate the outcome after Radium-223-dichloride (²²³RaCl₂) treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body ¹⁸F-Fluoride PET/CT. Sodium ¹⁸F-fluoride [¹⁸F]-NaF PET/CT was performed prior the treatment of ²²³RaCl₂, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in [¹⁸F]-NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with [¹⁸F]-NaF response, only 1 patient demonstrated progressive disease, i.e., >25% increase in S-PSA values during ²²³RaCl₂. Our results (although preliminary) suggest that ¹⁸F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases.

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for “go” versus “no go” decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords “response assessment” and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of “omics in radiology”—radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

IQ·SPECT (Siemens Medical Solutions) is a solution for high-sensitivity and short-time acquisition imaging of the heart for a variable angle general purpose gamma camera. It consists of a multi-focal collimator, a cardio-centric orbit and advanced iterative reconstruction, modeling the image formation physics accurately. The multi-focal collimator enables distance-dependent enlargement of the center region while avoiding truncation at the edges. With the specified configuration and a cardio-centric orbit it can obtain a fourfold sensitivity increase for the heart at the center of the scan orbit. Since IQ·SPECT shows characteristic distribution patterns in the myocardium, appropriate acquisition and processing conditions are required, and normal databases are convenient for quantification of both normal and abnormal perfusion images. The use of prone imaging can be a good option when X-ray computed tomography (CT) is not available for attenuation correction. CT-based attenuation correction changes count distribution significantly in the inferior wall and around the apex, hence image interpretation training and additional use of normal databases are recommended. Recent reports regarding its technology, Japanese Society of Nuclear Medicine working group activities, and clinical studies using ²⁰¹Tl and ^99mTc-perfusion tracers in Japan are summarized.

The IQ·SPECT system was introduced by Siemens in 2010 to significantly improve the efficiency of myocardial perfusion imaging (MPI) using conventional, large field-of-view (FOV) SPECT and SPECT·CT systems. With IQ·SPECT, it is possible to perform MPI scans in one-fourth the time or using one-fourth the administered dose as compared to a standard protocol using parallel-hole collimators. This improvement is achieved by means of a proprietary multifocal collimator that rotates around the patient in a cardio-centric orbit resulting in a four-fold magnification of the heart while keeping the entire torso in the FOV. The data are reconstructed using an advanced reconstruction algorithm that incorporates measured values for gantry deflections, collimator-hole angles, and system point response function. This article explores the boundary conditions of IQ·SPECT imaging, as measured using the Data Spectrum ^® cardiac torso phantom with the cardiac insert. Impact on reconstructed image quality was evaluated for variations in positioning of the myocardium relative to the sweet spot, scan-arc limitations, and for low-dose imaging protocols. Reconstructed image quality was assessed visually using the INVIA 4DMSPECT and quantitatively using Siemens internal IQ assessment software. The results indicated that the IQ·SPECT system is capable of tolerating possible mispositioning of the myocardium relative to the sweet spot by the operator, and that no artifacts are introduced by the limited angle coverage. We also found from the study of multiple low dose protocols that the dwell time will need to be adjusted in order to acquire data with sufficient signal-to-noise ratio for good reconstructed image quality.