Patient management in oncology increasingly relies upon imaging for diagnosis, response assessment, and follow-up. The clinical availability of combined functional-anatomic imaging modalities, which integrate the benefits of visualizing tumor biology with those of high-resolution structural imaging, revolutionized clinical management of oncologic patients.[1–6] Conventional high resolution anatomic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) excel at providing details regarding lesion location, size, morphology, and structural changes to adjacent tissues; however, these modalities provide little insight into tumor physiology. With the increasing focus on molecularly targeted therapies, imaging radiolabeled compounds with positron emission tomography (PET) and single photon emission tomography (SPECT) are often used to provide insight into a tumor's biologic functions and its surrounding microenvironment. Despite their high sensitivity and specificity, PET and SPECT alone are substantially limited by low spatial resolution and inability to provide anatomic detail. Integrating SPECT or PET with a modality capable of providing these (i.e. CT or MR) maximizes their separate strengths and provides anatomic localization of physiologic processes with detailed visualization of a tumor's structure. The availability of multi-modality (hybrid) imaging with PET/CT, SPECT/CT and PET/MR improves our ability to characterize lesions and to affect treatment decisions and patient management. We have just begun to exploit the truly synergistic capabilities of multi-modality imaging. Continued advances in instrumentation and imaging agent development will improve our ability to noninvasively characterize disease processes. This review will discuss the evolution of hybrid imaging technology and provide examples of its current and potential future clinical uses.

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F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa. METHODS 39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology. RESULTS 11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry. CONCLUSION 11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy, where tissue damage after therapy may limit anatomic imaging methods.

Our objective was to investigate the lesion detection rate of 18 F-DCFPyL PET/CT, a prostate-specific membrane antigen (PSMA)targeted PET agent, in patients with biochemically relapsed prostate cancer after primary local therapy. Methods: This was a prospective institutional review board-approved study of 90 patients with documented biochemical recurrence (median prostate-specific antigen [PSA], 2.5 ng/mL; range, 0.21-35.5 ng/mL) and negative results on conventional imaging after primary local therapies, including radical prostatectomy (n 5 38), radiation (n 5 27), or a combination of the two (n 5 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body 18 F-DCFPyL PET/CT (299.9 ± 15.5 MBq) at 2 h after injection. The PSMA PET lesion detection rate was correlated with PSA, PSA kinetics, and original primary tumor grade. Results: Seventy patients (77.8%) showed positive PSMA PET results, with a total of 287 lesions identified: 37 prostate bed foci, 208 lesions in lymph nodes, and 42 in distant sites in bones or organs, Eleven patients had negative results, and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n 5 10/21), 50% (n 5 5/10), 88.9% (n 5 8/9), and 94% (n 5 47/50) for PSA levels of .0.2 to ,0.5, 0.5 to ,1.0, 1 to ,2.0, and $2.0 ng/mL, respectively. In postsurgical patients, PSA, PSA doubling time, and PSA velocity correlated with PET results, but the same was not true for postradiation patients. These parameters also correlated with the extent of disease on PET (intrapelvic vs. extrapelvic). There was no significant difference in the rate of positive scans between patients with higher-grade and lower-grade primary tumors (Gleason score of $4 1 3 vs. ,3 1 4). Tumor recurrence was histologyconfirmed in 40% (28/70) of patients. On a per-patient basis, positive predictive value was 93.3% (95% confidence interval, 77.6%-99.2%) by histopathologic validation and 96.2% (95% confidence interval, 86.3%-99.7%) by the combination of histology and imaging/clinical follow-up. Conclusion: 18 F-DCFPyL PET/CT imaging offers high detection rates in biochemically recurrent prostate cancer patients and is positive in about 50% of patients with a PSA level of less than 0.5 ng/mL, which could substantially impact clinical management. In postsurgical patients, 18 F-DCFPyL PET/CT correlates with PSA, PSA doubling time, and PSA velocity, suggesting it may have prognostic value. 18 F-DCFPyL PET/CT is highly promising for localizing sites of recurrent prostate cancer.

F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but results are dependent on PSA levels. Above a threshold PSA value of 0.78 ng/mL, F-DCFBC was able to identify recurrence with high reliability. PositiveF-DCFBC PET imaging led clinicians to change treatment strategy in 51.2% of patients.

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The current research-based evidence on PET imaging has demonstrated encouraging potential in the initial diagnosis and detection of recurrence and metastases of prostate cancer.