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Theranostics describes the coupling of a diagnostic biomarker and a therapeutic agent (i.e., a theranostic pair) that share a common target in tumor cells or their microenvironment. The term is increasingly associated with in vivo nuclear medicine oncologic applications that couple diagnostic imaging from gamma radiation with concomitant localized high-energy particulate radiation to a tissue expressing the common target. Several theranostic pairs have been translated into clinical practice in the United States and are poised to become a mainstay for cancer treatment. This article reviews experience to date with theranostics for solid-organ malignancies, addressing the practical integration into care pathways of beta-emitting therapies that include somatostatin analog radioligands for neuroendocrine tumors, prostate-specific membrane antigen-directed therapy for prostate cancer, and 131I-MIBG therapy for tumors of neural crest origin. Toxicities related to theranostics administration, as well as indications for therapy cessation in patients who experience adverse events, are also discussed. A multidisciplinary team-based approach for identifying patients most likely to respond to these agents, determining the optimal time for therapy delivery, and managing their care throughout the therapy course, is critical to the success of a radiotheranostic program.

Prostate-specific membrane antigen (PSMA) theranostics has been a momentous triumph for nuclear medicine. The recent approvals of PSMA-targeted imaging agents (

Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy. We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed. Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes. PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.

Background The aim of this exploratory preclinical study was to evaluate the efficacy of 18F-FMAU PET in quantitatively measuring response to a chemotherapeutic agent in experimental prostate cancer models. Methods and Materials: Docetaxel (DTX) ‒ a standard therapy agent in castrate-resistant metastatic prostate cancer was used as the chemotherapy drug. Athymic male nu/nu mice were inoculated with PC-3 cells in the right flank. After the tumor diameter reached 5 mm, DTX (24 mg/kg) was injected intravenously twice/week, whereas the control group was intravenously administered with saline. During the therapeutic period, the tumor size and body weight were monitored, and longitudinal PET scans were acquired with 18F-FMAU to evaluate tumor cell proliferation. 18F-FMAU PET scans were performed at 2 h post-injection of 18F-FMAU on days 0, 11, 18, and 22. Biodistribution studies were carried out after the PET scan on day 22. Results Consecutive administrations of DTX were effective in inhibiting PC-3 tumor growth compared to the control group. For PET imaging, PC-3 tumor uptake of 18F-FMAU in the treatment group was increased significantly from 3.09 ± 0.60%ID/g (day 0) to 5.32 ± 0.37%ID/g (day 22), whereas the 18F-FMAU tumor update in the control group remained relatively similar on day 0 (2.37 ± 0.51%ID/g) vs. day 22 (1.83 ± 0.22%ID/g). The tumor-to-muscle uptake ratio of 18F-FMAU was increased from 2.63 ± 0.20 (day 0) to 5.91 ± 1.1 (day 22) in the treatment group. On day 22, no statistical significance was observed on the tumor-to-muscle uptake ratio of 18F-FMAU in the treatment group vs. the control group. The tumor-to-liver uptake ratio of 18F-FMAU was also similar on day 22 in the treatment group (4.29 ± 0.09) vs. the control group (3.83 ± 0.59). Conclusion 18F-FMAU uptake in implanted PC-3 tumors increases with DTX treatment despite the decline in tumor size. Further investigation is needed to decipher the underlying biological mechanism of this flare effect and its relation to the predictability of therapy response.

Background F-Fluciclovine is the most recent prostate cancer (PCa)-directed PET radiotracer approved by the US Food and Drug Administration for detection of recurrent PCa. We report the treatments and outcomes of patients at our institution with PCa recurrences detected on F-fluciclovine PET/CT. Methods We identified men with recurrent PCa detected on F-fluciclovine PET/CT performed between 2017 and 2018 who were previously treated definitively and analyzed their patterns of care and cancer-specific outcomes. Results We identified 28 men with recurrent PCa detected on F-fluciclovine PET/CT. Twenty-three were initially treated with surgery and 13 also received postoperative radiation therapy (RT). Five patients were initially treated with definitive radiation. After surgery, the median time to F-fluciclovine PET/CT was 67 months (median prostate-specific antigen [PSA] of 1.63 ng/mL). After RT, the median time to F-fluciclovine PET/CT was 95 months with median PSA of 13.31 ng/mL. Six men recurred locally, 9 recurred in the pelvic nodes, 9 had distant nodal recurrences, and 4 had osseous metastases. Of the patients initially treated with surgery, 4 received salvage radiation and 3 received androgen deprivation therapy (ADT). Of the patients initially treated with surgery and postoperative RT, 3 received salvage pelvic nodal dissection, 4 received salvage radiation, and 2 received ADT. Of the patients initially treated with radiation, 4 received salvage ADT. All had PSA decline after salvage therapy. Conclusions F-fluciclovine PET/CT can localize PCa recurrences, and subsequent salvage therapies appear effective with decreasing PSA. Longer follow-up will reveal if these diagnostic tests and subsequent therapies will improve PCa survival.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumor such as prostate cancer requires the expansion of existing and the establishment of new theranostics centers. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostic centers. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Metastatic prostate cancer is not curable. There have been major strides in the treatment of patients with castration-resistant prostate cancer with many available therapeutic options which generally prolong the overall survival about an average of 4 months. The more recent advances are in immunotherapy and targeted radionuclide therapy, which are the focus of this chapter. We review the current evidence in these arenas and comment on future developments that are anticipated to transform the treatment landscape of patients with metastatic prostate cancer.

More widespread use of positron emission tomography (PET) imaging is limited by its high cost and radiation dose. Reductions in PET scan time or radiotracer dosage typically degrade diagnostic image quality (DIQ). Deep-learning-based reconstruction may improve DIQ, but such methods have not been clinically evaluated in a realistic multicenter, multivendor environment. In this study, we evaluated the performance and generalizability of a deep-learning-based image-quality enhancement algorithm applied to fourfold reduced-count whole-body PET in a realistic clinical oncologic imaging environment with multiple blinded readers, institutions, and scanner types. We demonstrate that the low-count-enhanced scans were noninferior to the standard scans in DIQ (p 0.05) and overall diagnostic confidence (p 0.001) independent of the underlying PET scanner used. Lesion detection for the low-count-enhanced scans had a high patient-level sensitivity of 0.94 (0.83-0.99) and specificity of 0.98 (0.95-0.99). Interscan kappa agreement of 0.85 was comparable to intrareader (0.88) and pairwise inter-reader agreements (maximum of 0.72). SUV quantification was comparable in the reference regions and lesions (lowest p-value=0.59) and had high correlation (lowest CCC = 0.94). Thus, we demonstrated that deep learning can be used to restore diagnostic image quality and maintain SUV accuracy for fourfold reduced-count PET scans, with interscan variations in lesion depiction, lower than intra- and interreader variations. This method generalized to an external validation set of clinical patients from multiple institutions and scanner types. Overall, this method may enable either dose or exam-duration reduction, increasing safety and lowering the cost of PET imaging.

More widespread use of positron emission tomography (PET) imaging is limited by its high cost and radiation dose. Reductions in PET scan time or radiotracer dosage typically degrade diagnostic image quality (DIQ). Deep-learning-based reconstruction may improve DIQ, but such methods have not been clinically evaluated in a realistic multicenter, multivendor environment. In this study, we evaluated the performance and generalizability of a deep-learning-based image-quality enhancement algorithm applied to fourfold reduced-count whole-body PET in a realistic clinical oncologic imaging environment with multiple blinded readers, institutions, and scanner types. We demonstrate that the low-count-enhanced scans were noninferior to the standard scans in DIQ (p p p-value=0.59) and had high correlation (lowest CCC = 0.94). Thus, we demonstrated that deep learning can be used to restore diagnostic image quality and maintain SUV accuracy for fourfold reduced-count PET scans, with interscan variations in lesion depiction, lower than intra- and interreader variations. This method generalized to an external validation set of clinical patients from multiple institutions and scanner types. Overall, this method may enable either dose or exam-duration reduction, increasing safety and lowering the cost of PET imaging.

A 51-year-old man diagnosed with high-grade, high-volume metastatic castration-sensitive prostate adenocarcinoma received pelvic radiation, androgen deprivation therapy, and intravenous docetaxel. Serum prostate-specific antigen became undetectable following treatment. Within a year, his cancer progressed to castration-resistant disease, and he was treated with oral abiraterone acetate 1000 mg and prednisone 10 mg daily. Despite this, the serum prostate-specific antigen rose from 0.03 to 1.39 μg/L, and F-DCFPyL and F-FDG PET/CT showed progression. While F-DCFPyL uptake may be seen in aggressive disease, F-FDG portends poor prognosis. Despite intravenous platinum-based chemotherapy, the patient died of respiratory failure 20 months after his initial diagnosis.

OBJECTIVE. The purpose of this study is to provide a concise summary of the current experience with (68)Ga-labeled prostate-specific membrane antigen (PSMA)–11 imaging of prostate and nonprostate malignancies and benign conditions. CONCLUSION. PSMA is overexpressed in prostate cancer and in the neovasculature of many other malignancies. The relevance of PSMA as a biologic target, coupled with advances in the design, synthesis, and evaluation of PSMA-based radionuclides for imaging and therapy, is anticipated to play a major role in patient care.

PURPOSE: The aims of this study were to report on our initial experience using (18)F-fluciclovine PET/CT to detect recurrent prostate carcinoma in patients with low serum prostate-specific antigen (PSA) after definitive treatment of primary disease and to conduct a preliminary investigation for factors associated with positive scan findings. PATIENTS AND METHODS: In this retrospective study, (18)F-fluciclovine PET/CT scans from 28 men with suspected recurrence of prostate carcinoma and PSAvalues of 1 ng/mL or less were examined to identify the site(s) of disease recurrence. Differences in detection rate for Gleason scores of 7 and greater than 7, T2 and T3 disease, negative and positive surgical margins, and negative and positive seminal vesicle invasion were compared using the Fisher exact test. Mean PSA and mean PSA doubling time of patients with positive scans and negative scans were compared using the independent 2-group t test. RESULTS: At least one site of disease recurrence was identified in 13 (46.4%) of 28 patients. Disease detection rate was significantly higher in patients with history of Gleason score greater than 7 (Fisher exact test, P = 0.004). Mean PSA and PSA doubling time were not significantly different between patients with positive and negative (18)F-fluciclovine PET/CT scans (P = 0.29 and 0.70, respectively). CONCLUSIONS: Detection of recurrent prostate cancer using (18)F-fluciclovine PET/CT is possible in patients with low but rising PSA levels of 1 ng/mL or less. In such patients, local and nodal recurrences are more common than distant metastasis, and Gleason score greater than 7 is associated with positive scan results.

Knowledge of the PET imaging findings of osseous spinal neoplasms is essential, because they are common incidental findings on PET scans done for staging of unrelated primary malignancies. Additionally, PET can help differentiate lesions that are not clearly defined by anatomic modalities alone. PET can also be used for follow-up of aggressive tumors to assess response to treatment, often proving superior to CT or MR imaging alone for this purpose. This review discusses the role of PET/CT and PET/MR imaging in the diagnosis and management of primary benign and malignant osseous tumors of the spine.

Progress in unraveling the complex biology of cancer, novel developments in radiochemistry, and availability of relevant α-emitters for targeted therapy have provided innovative approaches to precision cancer management. The approval of 223Ra dichloride for treatment of men with osseous metastatic castrate-resistant prostate cancer unleashed targeted α-therapy as a safe and effective cancer management strategy. While there is currently active research on new α-therapy regimens for prostate cancer based on the prostate-specific membrane antigen, there is emerging development of radiopharmaceutical therapy with a range of biological targets and α-emitting radioisotopes for malignancies other than the prostate cancer. This article provides a brief review of preclinical and first-in-human studies of targeted α-therapy in the cancers of brain, breast, lung, gastrointestinal, pancreas, ovary, and the urinary bladder. The data on leukemia, melanoma, myeloma, and neuroendocrine tumors will also be presented. It is anticipated that with further research the emerging role of targeted α-therapy in cancer management will be defined and validated.

PURPOSE: The goal of our retrospective single tertiary academic medical center investigation was to examine the added diagnostic value and clinical impact of (68)Ga-DOTATATE PET/CT in the therapeutic management of patients with neuroendocrine tumors (NETs). METHODS: Imaging database was queried for all “PET-DOTATATE” examinations performed at our tertiary care academic institution using MONTAGE™. The patient’s clinical history and recent prior imaging were reviewed. The additional diagnostic value and clinical management impact of (68)Ga-DOTATATE were assessed through retrospective chart review. RESULTS: A total of 81 (68)Ga-DOTATATE PET/CT scans in 74 patients were found, and 11 patients were excluded from analysis as they had no prior imaging available for comparison, with resultant analysis cohort of 63 patients. Six patients had 2 or more (68)Ga-DOTATATE PET/CT examinations. The most common primary diagnosis was undifferentiated NET (63.5%), followed by carcinoid (27.0%), paraganglioma (4.8%), insulinoma (3.2%), and pheochromocytoma (1.6%). The primary sites of disease from the most to the least common were the pancreas (36.5%), small bowel (22.2%), unknown primary (15.9%), lung (6.3%), large bowel (6.3%), and mesentery (4.8%), and other locations accounted for 7.9%. In patients who had prior imaging available for comparison, there were new lesions identified on (68)Ga-DOTATATE PET/CT in 21 patients (33.3%) that were not identified on other prior imaging modalities. Of these patients, 5 underwent subsequent MRI and 1 had a repeat (68)Ga-DOTATATE PET/CT to further characterize new lesions seen. Moreover, 15 patients (23.8%) had a change in treatment plan, including altering medical therapy in 9 patients, change in planned extent of surgical management in 5 patients, and cancelation of a planned primary tumor resection in 1 patient with metastatic disease. CONCLUSION: Our retrospective cohort demonstrated that (68)Ga-DOTATATE PET/CT improves lesion detection over conventional imaging in 33.3% and impacts the therapeutic management in 23.8% of patients with NET.

Infection of the heart with or without cardiac devices or prosthetic valves remains a serious disease that requires accurate diagnosis and early and adequate treatment to improve patient outcome. The modified Duke criteria are considered the standard of reference for diagnosing infective endocarditis and are based on clinical, microbiological, pathological, and echocardiographic findings. However, the Duke classification scheme can be inconclusive in detecting the presence and extent of infection. Transthoracic and transesophageal echocardiography have been the cornerstone imaging modality for evaluation of the heart. However, echocardiography is relatively insensitive in detecting early or subtle infection-related morphological changes and in distinguishing infected valve vegetations from structural changes in successfully treated valves. Single-photon radiolabeled leukocytes or positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) have been the most commonly used nuclear imaging techniques in the assessment of infective endocarditis. Systematic reviews and meta-analyses support the utility of nuclear imaging in cardiac infection. FDG PET may have a competitive advantage over radiolabeled leukocyte scintigraphy since it does not require blood draw for leukocyte labeling, and in conjunction with computed tomography (CT) provides anatomic correlation for accurate localization of infectious foci both within and outside of the heart.

Twenty-five years ago, oligometastatic disease was proposed as an intermediary clinical state of cancer with unique implications for therapies that may impact cancer evolution and patient outcome. Identification of limited metastases that are potentially amenable to targeted therapies fundamentally depends on the sensitivity of diagnostic tools, including new-generation imaging methods. For men with biochemical recurrence after definitive therapy of the primary prostate cancer, PET/CT using either the FDA-approved radiolabeled amino acid analogue

Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy.We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed.Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes.PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.

PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.

Soft tissue sarcomas (STSs) account for less than 1% of adult solid tumors and about 7% of pediatric malignancies, causing 2% of cancer-related deaths. With the advent of PET-computed tomography (CT), the value of (18) fluorine-2-fluoro-2-deoxy-d-glucose (FDG) PET imaging to improve the management of STSs has been explored. FDG PET imaging has been found useful in restaging and treatment response assessment. This article reviews current knowledge and application of FDG PET-CT in initial diagnosis, staging, restaging, treatment response monitoring, and prognosis, with a brief overview of the most common histologic subtypes of STS.

Imaging is often used to evaluate men with biochemical recurrence (BCR) of prostate cancer after definitive primary treatment (radical prostatectomy [RP] or radiotherapy [RT]). The goal of imaging is to identify the source of elevated or rising serum prostate-specific antigen (PSA) levels because

The fundamental foundation for precision medicine is accurate and specific targeting of cancer cells. Advances in the understanding of cancer biology, developments in diagnostic technologies, and expansion of therapeutic options have all contributed to the concept of personalized cancer care. Theranostics is the systematic integration of targeted diagnostics and therapeutics. The theranostic platform includes an imaging component that "sees" the lesions followed by administration of the companion therapy agent that "treats" the same lesions. This strategy leads to enhanced therapy efficacy, manageable adverse events, improved patient outcome, and lower overall costs. Radiotheranostics refers to the use of radionuclides for the paired imaging and therapy agents. Radioiodine is the classic radiotheranostic agent that has been used clinically in management of thyroid diseases for nearly 75 years. More recently there have been major exciting strides in radiotheranostics for neuroendocrine tumors and prostate cancer, among other conditions. Regulatory approval of a number of radiotheranostic pairs is anticipated in the near future. Continued support will be needed in research and development to keep pace with the current momentum in radiotheranostics innovations. Moreover, regulatory and reimbursement agencies need to streamline their requirements for seamless transfer of the radiotheranostic agents from the bench to the bedside. In this review, the concept, history, recent developments, current challenges, and outlook for radiotheranostics in the treatment of patients with cancer will be discussed.

Positron Emission Tomography (PET) is often underutilized in the field of musculoskeletal imaging, with key reasons including the excellent performance of conventional musculoskeletal MRI, the limited spatial resolution of PET, and the lack of reimbursement for PET for non-oncologic musculoskeletal indications. However, with improvements in PET/CT and PET/MR imaging over the last decade as well as an increased understanding of the pathophysiology of musculoskeletal diseases, there is an emerging potential for PET as a primary or complementary modality in the management of rheumatologic and orthopedic patients. Specific advantages of PET include the convenience of whole body imaging in a single session, the relative resilience of the modality in the imaging of metallic implants compared to CT and MRI, the ability to evaluate deep joints not amenable to palpation, and the potential for improved specificity of diagnosis with novel radiopharmaceuticals. In this review, we discuss multiple radiopharmaceuticals and technical consideration of PET/CT and PET/MRI that can be employed in imaging of non-tumoral bone and soft tissue disorders. Both PET/CT and PET/MR hold significant promise in the field of musculoskeletal imaging, and with further radiopharmaceutical development and clinical research, these hybrid modalities can potentially transform the current management of patients with orthopedic and rheumatologic disease.

A 73-year-old woman with history of metastatic basal cell carcinoma presented with a large spinal mass demonstrating a high mutational burden of 111 mutations/Mb. She underwent T12 corpectomy and T10-L3 posterior spinal fusion followed by adjuvant radiation. After 2 years of surveillance, FDG PET/CT and a contrast-enhanced MRI revealed recurrence, prompting salvage therapy with the hedgehog signaling pathway inhibitor, sonidegib, which only transiently stabilized the disease. An off-label treatment with the programmed death protein 1 inhibitor, pembrolizumab, was initiated. Serial FDG PET/CT showed gradual decline in tumor metabolism over the next 12 months, leading to complete metabolic response.