Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

PET Imaging of Metabolism, Perfusion, and Hypoxia: FDG and Beyond.

ABSTRACT: Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and guide targeted treatment.

Mycobacterial spindle cell pseudotumor of the spinal cord: Case report and literature review.

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.

68 Ga-DOTATATE PET to Characterize Lesions in the Neuroaxis.

AIM: The differentiation of paragangliomas, schwannomas, meningiomas, and other neuroaxis tumors in the head and neck remains difficult when conventional MRI is inconclusive. This study assesses the utility of 68 Ga-DOTATATE PET/CT as an adjunct to hone the diagnosis. PATIENTS AND METHODS: This retrospective study considered 70 neuroaxis lesions in 52 patients with 68 Ga-DOTATATE PET/CT examinations; 22 lesions (31%) had pathologic confirmation. Lesions were grouped based on pathological diagnosis and best radiologic diagnosis when pathology was not available. Wilcoxon rank sum tests were used to test for differences in SUV max among paragangliomas, schwannomas, and meningiomas. Receiver operator characteristic curves were constructed. RESULTS: Paragangliomas had a significantly greater 68 Ga-DOTATATE uptake (median SUV max , 62; interquartile range [IQR], 89) than nonparagangliomas. Schwannomas had near-zero 68 Ga-DOTATATE uptake (median SUV max , 2; IQR, 1). Intermediate 68 Ga-DOTATATE uptake was seen for meningiomas (median SUV max , 19; IQR, 6) and other neuroaxis lesions (median SUV max , 7; IQR, 9). Receiver operator characteristic analysis demonstrated an area under the curve of 0.87 for paragangliomas versus all other lesions and 0.97 for schwannomas versus all other lesions. CONCLUSIONS: Marked 68 Ga-DOTATATE uptake (>50 SUV max ) favors a diagnosis of paraganglioma, although paragangliomas exhibit a wide variability of uptake. Low to moderate level 68 Ga-DOTATATE uptake is nonspecific and may represent diverse pathophysiology including paraganglioma, meningioma, and other neuroaxis tumors but essentially excludes schwannomas, which exhibited virtually no uptake.

Fluorine-18-Labeled Fluoroestradiol PET/CT: Current Status, Gaps in Knowledge, and Controversies-AJR Expert Panel Narrative Review.

PET/CT using 16α-[18F]-fluoro-17ß-estradiol (FES) noninvasively images tissues expressing estrogen receptors (ERs). FES has undergone extensive clinicopathologic validation for ER+ breast cancer and received FDA approval in 2020 for clinical use as an adjunct to biopsy in patients with recurrent or metastatic ER+ breast cancer. Clinical use of FES PET/CT is increasing, but is not widespread in the United States. This AJR Expert Panel Narrative Review explores the present status and future directions of FES PET/CT, including image interpretation, existing and emerging uses, knowledge gaps, and current controversies. Specific controversies discussed include whether both FES PET/CT and FDG PET/CT are warranted in certain scenarios, whether further workup is required after negative FES PET/CT results, whether FES PET/CT findings should inform endocrine therapy selection, and whether immunohistochemistry should remain the standalone reference standard for determining ER status for all breast cancers. Consensus opinions from the panel include agreement with the appropriate clinical uses of FES PET/CT published by a multidisciplinary expert workgroup in 2023; anticipated expanded clinical use of FES PET/CT for staging ER-positive invasive lobular carcinomas and low-grade invasive ductal carcinomas pending ongoing clinical trial results; and the need for further research regarding use of FES PET/CT for ER-expressing nonbreast malignancies.

PSMA Uptake in a Subdural Hematoma.

ABSTRACT: An 81-year-old man with known metastatic prostate cancer with recent biochemical progression underwent a PSMA PET/CT ( 18 F-piflufolastat) for restaging. Review of the images demonstrated an acute or chronic left cerebral convexity subdural hematoma on CT with corresponding radiotracer activity throughout the collection on PET. Analysis of the patient's prior imaging showed that this subdural hematoma had significantly increased in size when compared with a head CT obtained 2 months prior. The patient was referred to a nearby emergency department and underwent repeat imaging and subdural drain placement. Unfortunately, the patient died secondary to rapid reaccumulation of subdural blood products after intervention.

Other Novel PET Radiotracers for Breast Cancer.

Many novel PET radiotracers have demonstrated potential use in breast cancer. Although not currently approved for clinical use in the breast cancer population, these innovative imaging agents may one day play a role in the diagnosis, staging, management, and even treatment of breast cancer.

Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging in Radiation Therapy Treatment Planning: A Review of PET Imaging Tracers and Methods to Incorporate PET/CT.

Purpose: Positron emission tomography (PET)/computed tomography (CT) has become a critical tool in clinical oncology with an expanding role in guiding radiation treatment planning. As its application and availability grows, it is increasingly important for practicing radiation oncologists to have a comprehensive understanding of how molecular imaging can be incorporated into radiation planning and recognize its potential limitations and pitfalls. The purpose of this article is to review the major approved positron-emitting radiopharmaceuticals clinically being used today along with the methods used for their integration into radiation therapy including methods of image registration, target delineation, and emerging PET-guided protocols such as biologically-guided radiation therapy and PET-adaptive therapy. Methods and Materials: A review approach was utilized using collective information from a broad review of the existing scientific literature sourced from PubMed search with relevant keywords and input from a multidisciplinary team of experts in medical physics, radiation treatment planning, nuclear medicine, and radiation therapy. Results: A number of radiotracers imaging various targets and metabolic pathways of cancer are now commercially available. PET/CT data can be incorporated into radiation treatment planning through cognitive fusion, rigid registration, deformable registration, or PET/CT simulation techniques. PET imaging provides a number of benefits to radiation planning including improved identification and delineation of the radiation targets from normal tissue, potential automation of target delineation, reduction of intra- and inter-observer variability, and identification of tumor subvolumes at high risk for treatment failure which may benefit from dose intensification or adaptive protocols. However, PET/CT imaging has a number of technical and biologic limitations that must be understood when guiding radiation treatment. Conclusion: For PET guided radiation planning to be successful, collaboration between radiation oncologists, nuclear medicine physicians, and medical physics is essential, as well as the development and adherence to strict PET-radiation planning protocols. When performed properly, PET-based radiation planning can reduce treatment volumes, reduce treatment variability, improve patient and target selection, and potentially enhance the therapeutic ratio accessing precision medicine in radiation therapy.

18F-Fluoroestradiol: Current Applications and Future Directions.

In the United States, breast cancer is the second leading cause of cancer death in all women and the leading cause of cancer death in Black women. The breast cancer receptor profile, assessed with immunohistochemical staining of tissue samples, allows prediction of outcomes and direction of patient treatment. Approximately 80% of newly diagnosed breast cancers are hormone receptor (HR) positive, which is defined as estrogen receptor (ER) and/or progesterone receptor (PR) positive. Patients with ER-positive disease can be treated with therapies targeting the ER; however, the assessment of ER expression with immunohistochemical staining of biopsy specimens has several limitations including sampling error, false-negative results, challenging or inaccessible biopsy sites, and the inability to synchronously and serially assess all metastatic sites to identify spatial and/or temporal ER heterogeneity. In May 2020, after decades of research, the U.S. Food and Drug Administration approved the PET radiotracer fluorine 18 (18F) fluoroestradiol (FES) for clinical use in patients with ER-positive recurrent or metastatic breast cancer as an adjunct to biopsy. FES binds to the ER in the nucleus of ER-expressing cells, enabling whole-body in vivo assessment of ER expression. This article is focused on the approved uses of FES in the United States, including identification of a target lesion for confirmatory biopsy, in vivo assessment of biopsy-proven ER-positive disease, and evaluation of spatial and temporal ER heterogeneity. FES is an example of precision medicine that has been leveraged to optimize the care of patients with breast cancer. © RSNA, 2023 See the invited commentary by Fowler in this issue. Quiz questions for this article are available through the Online Learning Center.

Widespread micronodular hepatic metastases of neuroendocrine tumor detected by [68Ga]DOTATATE PET/CT.

Neuroendocrine tumors (NET) encompass a diverse, heterogeneous group of neoplasms that originate from the secretory cells of the neuroendocrine system. These neoplasms typically express the somatostatin receptor (SSTR), which can be targeted by molecular agents for imaging and therapy. This is particularly advantageous for imaging NETs that are indolent, slow-growing, and less well detected by [18F]FDG and for the detection of occult disease not easily identified by anatomic imaging. Herein, we present a case in which [68Ga]DOTATATE PET/CT was used to diagnose the etiology of biochemical recurrence in NET that was not apparent on MRI. The importance of understanding deviations from the normal biodistribution of the radiotracer is emphasized as key in interpreting nuclear medicine studies and establishing the diagnosis. Imaging the SSTR is of particular interest given the recent FDA approval of [68Cu]DOTATATE as a new and possibly more available molecular radiotracer.

[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study.

PURPOSE: PARP inhibitors have become the standard-of-care treatment for homologous recombination deficient (HRD) high-grade serous ovarian cancer (HGSOC). However, not all HRD tumors respond to PARPi. Biomarkers to predict response are needed. [18F]FluorThanatrace ([18F]FTT) is a PARPi-analog PET radiotracer that noninvasively measures PARP-1 expression. Herein, we evaluate [18F]FTT as a biomarker to predict response to PARPi in patient-derived xenograft (PDX) models and subjects with HRD HGSOC. EXPERIMENTAL DESIGN: In PDX models, [18F]FTT-PET was performed before and after PARPi (olaparib), ataxia-telangiectasia inhibitor (ATRi), or both (PARPi-ATRi). Changes in [18F]FTT were correlated with tumor volume changes. Subjects were imaged with [18F]FTT-PET at baseline and after ∼1 week of PARPi. Changes in [18F]FTT-PET uptake were compared with changes in tumor size (RECISTv1.1), CA-125, and progression-free survival (PFS). RESULTS: A decrease in [18F]FTT tumor uptake after PARPi correlated with response to PARPi, or PARPi-ATRi treatment in PARPi-resistant PDX models (r = 0.77-0.81). In subjects (n = 11), percent difference in [18F]FTT-PET after ∼7 days of PARPi compared with baseline correlated with best RECIST response (P = 0.01), best CA-125 response (P = 0.033), and PFS (P = 0.027). All subjects with >50% reduction in [18F]FTT uptake had >6-month PFS and >50% reduction in CA-125. Utilizing only baseline [18F]FTT uptake did not predict such responses. CONCLUSIONS: The decline in [18F]FTT uptake shortly after PARPi initiation provides a measure of drug-target engagement and shows promise as a biomarker to guide PARPi therapies in this pilot study. These results support additional preclinical mechanistic and clinical studies in subjects receiving PARPi ± combination therapy. See related commentary by Liu and Zamarin, p. 1384.

Distinguishing Progression from Pseudoprogression in Glioblastoma Using 18F-Fluciclovine PET.

Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUVmax (6.64 + 1.88 vs. 4.11 ± 1.52, P = 0.009) than patients with pseudoprogression. A 40- to 50-min SUVmax cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUVmax cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.

177Lu-PSMA Therapy.

Radiopharmaceutical therapy using 177Lu-prostate-specific membrane antigen (PSMA) is an effective prostate cancer treatment that was recently approved by the U.S. Food and Drug Administration. This method leverages the success of PSMA-targeted PET imaging, enabling delivery of targeted radiopharmaceutical therapy; has demonstrated a clear benefit in large prospective clinical trials; and promises to become part of the standard armamentarium of treatment for patients with prostate cancer. This review highlights the evidence supporting the use of this agent, along with important areas under investigation. Practical information on technology aspects, dose administration, nursing, and the role of the treating physician is highlighted. Overall, 177Lu-PSMA treatment requires close collaboration among referring physicians, nuclear medicine technologists, radiopharmacists, and nurses to streamline patient care.

Novel applications of molecular imaging to guide breast cancer therapy.

The goals of precision oncology are to provide targeted drug therapy based on each individual's specific tumor biology, and to enable the prediction and early assessment of treatment response to allow treatment modification when necessary. Thus, precision oncology aims to maximize treatment success while minimizing the side effects of inadequate or suboptimal therapies. Molecular imaging, through noninvasive assessment of clinically relevant tumor biomarkers across the entire disease burden, has the potential to revolutionize clinical oncology, including breast oncology. In this article, we review breast cancer positron emission tomography (PET) imaging biomarkers for providing early response assessment and predicting treatment outcomes. For 2-18fluoro-2-deoxy-D-glucose (FDG), a marker of cellular glucose metabolism that is well established for staging multiple types of malignancies including breast cancer, we highlight novel applications for early response assessment. We then review current and future applications of novel PET biomarkers for imaging the steroid receptors, including the estrogen and progesterone receptors, the HER2 receptor, cellular proliferation, and amino acid metabolism.

Principles of Tracer Kinetic Analysis in Oncology, Part II: Examples and Future Directions.

Learning Objectives: On successful completion of this activity, participants should be able to (1) describe examples of the application of PET tracer kinetic analysis to oncology; (2) list applications research and possible clinical applications in oncology where kinetic analysis is helpful; and (3) discuss future applications of kinetic modeling to cancer research and possible clinical cancer imaging practice.Financial Disclosure: This work was supported by KL2 TR001879, R01 CA211337, R01 CA113941, R33 CA225310, Komen SAC130060, R50 CA211270, and K01 DA040023. Dr. Pantel is a consultant or advisor for Progenics and Blue Earth Diagnostics and is a meeting participant or lecturer for Blue Earth Diagnostics. Dr. Mankoff is on the scientific advisory boards of GE Healthcare, Philips Healthcare, Reflexion, and ImaginAb and is the owner of Trevarx; his wife is the chief executive officer of Trevarx. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest.CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through April 2025.Kinetic analysis of dynamic PET imaging enables the estimation of biologic processes relevant to disease. Through mathematic analysis of the interactions of a radiotracer with tissue, information can be gleaned from PET imaging beyond static uptake measures. Part I of this 2-part continuing education paper reviewed the underlying principles and methodology of kinetic modeling. In this second part, the benefits of kinetic modeling for oncologic imaging are illustrated through representative case examples that demonstrate the principles and benefits of kinetic analysis in oncology. Examples of the model types discussed in part I are reviewed here: a 1-tissue-compartment model (15O-water), an irreversible 2-tissue-compartment model (18F-FDG), and a reversible 2-tissue-compartment model (3'-deoxy-3'-18F-fluorothymidine). Kinetic approaches are contrasted with static uptake measures typically used in the clinic. Overall, this 2-part review provides the reader with background in kinetic analysis to understand related research and improve the interpretation of clinical nuclear medicine studies with a focus on oncologic imaging.

Abbreviated scan protocols to capture 18F-FDG kinetics for long axial FOV PET scanners.

PURPOSE: Kinetic parameters from dynamic 18F-fluorodeoxyglucose (FDG) imaging offer complementary insights to the study of disease compared to static clinical imaging. However, dynamic imaging protocols are cumbersome due to the long acquisition time. Long axial field-of-view (LAFOV) PET scanners (> 70 cm) have two advantages for dynamic imaging over clinical PET scanners with a standard axial field-of-view (SAFOV; 16-30 cm). The large axial coverage enables multi-organ dynamic imaging in a single bed position, and the high sensitivity may enable clinically routine abbreviated dynamic imaging protocols. METHODS: In this work, we studied two abbreviated protocols using data from a 65-min dynamic 18F-FDG scan: (A) dynamic imaging immediately post-injection (p.i.) for variable durations, and (B) dynamic imaging immediately p.i. for variable durations plus a 1-h p.i. (5-min-long) datapoint. Nine cancer patients were imaged on the Biograph Vision Quadra (Siemens Healthineers). Time-activity curves over the lesions (N = 39) were fitted using the Patlak graphical analysis and a 2-tissue-compartment (2C, k4 = 0) model for variable scan durations (5-60 min). Kinetic parameters from the complete dataset served as the reference. Lesions from all cancers were grouped into low, medium, and high flux groups, and bias and precision of Ki (Patlak) and Ki, K1, k2, and k3 (2C) were calculated for each group. RESULTS: Using only early dynamic data with the 2C (or Patlak) model, accurate quantification of Ki required at least 50 (or 55) min of dynamic data for low flux lesions, at least 30 (or 40) min for medium flux lesions, and at least 15 (or 20) min for high flux lesions to achieve both 10% bias and precision. The addition of the final (5-min) datapoint allowed for accurate quantification of Ki with a bias and precision of 10% using only 10-15 min of early dynamic data for either model. CONCLUSION: Dynamic imaging for 10-15 min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify 18F-FDG on a long axial FOV scanner, potentially allowing for more widespread use of dynamic 18F-FDG imaging.