Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

SPECT at the speed of PET: a feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATATE and 177Lu-PSMA617 setting.

PURPOSE: To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals. METHODS: Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177Lu-DOTATATE (n=17) or 177Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64Cu-DOTATATE or 18F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read. RESULTS: This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans. CONCLUSION: Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies.

Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy.

PURPOSE: The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated. RESULTS: The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group. CONCLUSION: Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.

Preclinical SPECT and SPECT-CT in Oncology.

Molecular imaging enables both spatial and temporal understanding of the complex biologic systems underlying carcinogenesis and malignant spread. Single-photon emission tomography (SPECT) is a versatile nuclear imaging-based technique with ideal properties to study these processes in vivo in small animal models, as well as to identify potential drug candidates and characterize their antitumor action and potential adverse effects. Small animal SPECT and SPECT-CT (single-photon emission tomography combined with computer tomography) systems continue to evolve, as do the numerous SPECT radiopharmaceutical agents, allowing unprecedented sensitivity and quantitative molecular imaging capabilities. Several of these advances, their specific applications in oncology as well as new areas of exploration are highlighted in this chapter.

Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor.

OBJECTIVE: To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. MATERIALS AND METHODS: Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. RESULTS: A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values <0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT. CONCLUSIONS: A simultaneous PET/MRI using both (68)Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. METHODS: Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H2(15)O positron emission tomography - computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRS(TMS)-NRS(placebo)) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. RESULTS: A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session. CONCLUSION: Multi-coil rTMS may be a safe and effective treatment option for acute as well as for chronic pain, such as that accompanying fibromyalgia. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments.

Native renal function after combined liver-kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium-99 m-mercaptoacetyltriglycine scans.

Type 1 hepatorenal syndrome (HRS) is characterized by rapid deterioration of renal function. We sought to assess native kidney function after combined kidney-liver transplant (CLKTx) performed for type 1 HRS. We performed a retrospective, cross-sectional, single-center study. All patients with Type 1 HRS who received a CLKTx at the University of California, San Francisco from 1997 to 2007 were screened for enrollment. Patients with a baseline estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2) were eligible. Twenty-three patients were identified and consented to receive a Technetium-99 m-mercaptoacetyltriglycine (MAG3) nuclear scan to measure the native kidney contribution to overall renal function. Only 4 of the 23 subjects (17.4%) demonstrated native renal function that consisted of a contribution ≥50% of total renal function. Several factors and comorbidities such as age, gender, race, duration of HRS, need for and duration of renal replacement therapy, need for pressors, urine sodium, proteinuria, and use of octreotide/midodrine were analyzed and not found to be significant in predicting native renal function. The assessment of post-transplant native renal function following CLKTx may allow for improved accuracy in identifying the patients in need of CLKTx, and thus allow for greater optimization of dual-organ allocation strategies in patients with concomitant liver and renal failure.

A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High-Intensity Focused Ultrasound Therapy.

Focal therapy for localized prostate cancer (PC) using high-intensity focused ultrasound (HIFU) is gaining in popularity as it is noninvasive and associated with fewer side effects than standard whole-gland treatments. However, better methods to evaluate response to HIFU ablation are an unmet need. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in PC. In this study, we evaluated a novel approach of using both 68Ga-RM2 and 68Ga-PSMA11 PET/MRI in each patient before and after HIFU to assess the accuracy of target tumor localization and response to treatment. Methods: Fourteen men, 64.5 ± 8.0 y old (range, 48-78 y), with newly diagnosed PC were prospectively enrolled. Before HIFU, the patients underwent prostate biopsy, multiparametric MRI, 68Ga-PSMA11, and 68Ga-RM2 PET/MRI. Response to treatment was assessed at a minimum of 6 mo after HIFU with prostate biopsy (n = 13), as well as 68Ga-PSMA11 and 68Ga-RM2 PET/MRI (n = 14). The SUVmax and SUVpeak of known or suspected PC lesions were collected. Results: Pre-HIFU biopsy revealed 18 cancers, of which 14 were clinically significant (Gleason score ≥ 3 + 4). Multiparametric MRI identified 18 lesions; 14 of them were at least score 4 in the Prostate Imaging-Reporting and Data System. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each showed 23 positive intraprostatic lesions; 21 were congruent in 13 patients, and 5 were incongruent in 5 patients. Before HIFU, 68Ga-PSMA11 identified all target tumors, whereas 68Ga-RM2 PET/MRI missed 2 tumors. After HIFU, 68Ga-RM2 and 68Ga-PSMA11 PET/MRI both identified clinically significant residual disease in 1 patient. Three significant ipsilateral recurrent lesions were identified, whereas 1 was missed by 68Ga-PSMA11. The pretreatment level of prostate-specific antigen decreased significantly after HIFU, by 66%. Concordantly, the pretreatment SUVmax decreased significantly after HIFU for 68Ga-PSMA11 (P = 0.001) and 68Ga-RM2 (P = 0.005). Conclusion: This pilot study showed that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the target tumor for HIFU in 100% and 86% of cases, respectively, and accurately verified response to treatment. PET may be a useful tool in the guidance and monitoring of treatment success in patients receiving focal therapy for PC. These preliminary findings warrant larger studies for validation.

A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer.

Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20%-65% of highly suspicious lesions on mpMRI (PI-RADS [Prostate Imaging-Reporting and Data System] 4 or 5) are false-positives (FPs), while 5%-10% of clinically significant PC (csPC) are missed. Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPRs) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0 ± 7.1 y, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI results or negative biopsy were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 min. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. The SUVmax of suspected PC lesions was collected and compared with gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8 ± 6.0 (range, 1.5-25.5) ng/mL and 0.20 ± 0.18 (range, 0.06-0.68) ng/mL2, respectively. Standardized systematic biopsy revealed a total of 14 PCs in 8 participants: 7 were csPC and 7 were nonclinically significant PC (ncsPC). 68Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true-positive (TP) (5 csPC). 68Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients versus 14 discordant lesions in 7 patients between 68Ga-PSMA11 and 68Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUVmax was significantly higher for TP than FP lesions in delayed pelvic imaging for 68Ga-PSMA11 (6.49 ± 4.14 vs. 4.05 ± 1.55, P = 0.023) but not for whole-body images, nor for 68Ga-RM2. Conclusion: Our results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68Ga-RM2 PET/MRI identified all csPC confirmed at biopsy.

Radiotheranostics - Precision Medicine in Nuclear Medicine and Molecular Imaging.

'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term theranostic was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives.

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE.

ABSTRACT: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions <3 cm in size. We present a 66-year-old man with pancreatic neuroendocrine carcinoma, who had a rapidly growing metastatic nodal conglomerate, which measured close to 10 cm in size. After only 2 cycles of PRRT with 177 Lu-DOTATATE, the nodal conglomerate had a striking size reduction greater than 75%. This case highlights the potential efficacy of PRRT with 177 Lu-DOTATATE for treatment of aggressive neuroendocrine neoplasms.

The Clinical Utility of 18F-Fluciclovine PET/CT in Biochemically Recurrent Prostate Cancer: an Academic Center Experience Post FDA Approval.

PURPOSE: To evaluate the diagnostic performance and clinical utility of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). METHODS: 18F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging (18F-NaF PET/CT (n = 12), 68Ga-PSMA11 PET/CT (n = 5), 18F-DCFPyL PET/CT (n = 20), and 68Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated. RESULTS: The overall positivity rate of 18F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA < 0.5), 50 % (0.5 ≤ PSA < 1), 56 % (1 ≤ PSA < 2), 68 % (2 ≤ PSA < 5), and 94 % (PSA ≥ 5), respectively. One hundred and two patients (62 %) had changes in clinical management based on 18F-fluciclovine PET findings. Twelve of these patients (12 %) had lesion localization on 18F-fluciclovine PET, despite negative conventional imaging. Treatment plans of 14 patients with negative 18F-fluciclovine PET were changed based on additional PET imaging with a different radiopharmaceutical. CONCLUSION: 18F-Fluciclovine PET/CT remains a useful diagnostic tool in the workup of patients with BCR PC, changing clinical management in 62 % of participants in our cohort.

Prognostic Value of Bone Marrow Metabolism on Pretreatment 18F-FDG PET/CT in Patients with Metastatic Melanoma Treated with Anti-PD-1 Therapy.

Our purpose was to investigate the prognostic value of 18F-FDG PET/CT parameters in melanoma patients before beginning therapy with antibodies to the programmed cell death 1 receptor (anti-PD-1). Methods: Imaging parameters including SUVmax, metabolic tumor volume, and the ratio of bone marrow to liver SUVmean (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. The association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data were compared between the high-BLR group (>median) and the low-BLR group (≤median). Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for progression-free and overall survival (P = 0.017 and P = 0.011, respectively). The high-BLR group had higher white blood cell counts and neutrophil counts and a higher level of C-reactive protein than the low-BLR group (P < 0.05). Conclusion: Patients with a high BLR were associated with poor progression-free and overall survival, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) with confirmed liver metastases negative on 18F-FDG and 68Ga-DOTATATE PET.

Lung neuroendocrine neoplasms (NENs) encompass the low-, intermediate-, and high-grade entities. Differentiated NENs overexpress somatostatin receptors, which are targeted by 68Ga-DOTA-conjugated peptides in molecular imaging with positron emission tomography. Less differentiated NENs may have lost their expression of somatostatin receptors and thus show lower uptake of 68Ga-DOTA-peptides; however, these tumors express GLUT-1 and can be imaged with (18)F-fluordeoxyglucose (FDG). We report the case of a 72-year-old patient with a poorly differentiated, high grade lung NEN, which was 18F-FDG-positive at initial diagnosis. After treatment and remission, the patient had histologically confirmed relapse in the liver. Interestingly, these hepatic metastases did not demonstrated radiopharmaceutical uptake at neither 18F-FDG nor 68Ga-DOTATATE positron emission tomography/computed tomography.

Comparison of 3 Interpretation Criteria for 68Ga-PSMA11 PET Based on Inter- and Intrareader Agreement.

PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent 68Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating 68Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue.

Prospective Evaluation of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer in an Academic Center: A Focus on Disease Localization and Changes in Management.

18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52-91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18F-fluciclovine PET/CT (18), or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results:18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with 18F-DCFPyL, whereas 18F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or 18F-NaF PET scans were congruent with 18F-DCFPyL PET, whereas 18F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or 18F-NaF PET scans. In 8 of 18 (44%) patients, 18F-fluciclovine PET had located the same lesions as did 18F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative 18F-fluciclovine findings had positive 18F-DCFPyL PET findings and 1 of 18 (6%) patients with negative 18F-DCFPyL findings had uptake in the prostate bed on 18F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, 18F-DCFPyL and 18F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative results on conventional imaging. Conclusion:18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration-approved currently available imaging modalities and its impact on clinical management in 60% of patients.

Fungal endocarditis resembling primary cardiac malignancy in a patient with B-cell ALL with culture confirmation.

Fungal endocarditis is a rare subtype of infective endocarditis that often presents with nonspecific symptoms in patients with complex medical histories, making diagnosis challenging. Patients with a history of ALL may present with congestive heart failure, chemo-induced cardiomyopathy, acute coronary syndrome, cardiac lymphomatous metastasis, or infections. We present the case of a patient with a history of ALL who presented with acute coronary syndrome and imaging concerning for primary cardiac lymphoma, when in fact the patient ended up suffering from culture proven fungal endocarditis.