Evaluation of Lung Cancer and Neuroendocrine Neoplasm in a Single Scan by Targeting Both Somatostatin Receptor and Integrin αvβ3 Purpose This pilot study aimed to prove the complementary value of a novel 68Gallium-labeled heterodimeric peptide, 68Ga-NOTA-3P-TATE-RGD, in detection and evaluation of tumors with somatostatin receptor subtype 2 or integrin αvβ3 overexpression, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), neuroendocrine tumor (NET), and neuroendocrine carcinoma (NEC). Methods With institute review board approval and written informed consent, 32 patients with pathologically diagnosed lung cancer (18 NSCLC, 14 SCLC) and 12 patients with neuroendocrine neoplasm (8 NET, 4 NEC) patients were recruited to undergo 68Ga-NOTA-3P-TATE-RGD PET/CT. For comparison, the NSCLC patients also underwent 68Ga-NOTA-TATE PET/CT, the SCLC patients underwent 68Ga-NOTA-RGD PET/CT, and the neuroendocrine neoplasm patients underwent 18F-FDG PET/CT within 3 days. The maximum standardized uptake value (SUV) of the primary tumor (T) and mean SUV of the blood pool (B) were measured, and the T/B ratios were calculated for comparison. Results In the primary tumors of NSCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-TATE (4.54 ± 3.00 versus 4.10 ± 2.83, P = 0.0058). In SCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-RGD (6.06 ± 6.09 versus 2.65 ± 1.19, P = 0.0344). In NET, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were 36.13 ± 33.84, significantly higher than those of 18F-FDG (2.91 ± 1.71, P = 0.0234). In NEC, there were no significant difference between the T/B ratios of 68Ga-NOTA-3P-TATE-RGD (4.80 ± 0.85) and those of 18F-FDG (3.56 ± 0.74, P = 0.1833). Conclusions This proof-of-concept study preliminarily demonstrates the efficacy of the dual targeting 68Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of lung cancer and neuroendocrine neoplasm in a single scan.

Clinical Utility of Different Approaches for Detection of Late Pseudoprogression in Glioblastoma With O-(2-[18F]Fluoroethyl)-L-Tyrosine PET Purpose PET/CT using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM). Methods Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared. Results 18F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P > 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior. Conclusions Irrespective of the analytical approach, 18F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers.

Evidence of Prostate-Specific Membrane Antigen Expression in Hepatocellular Carcinoma Using 68Ga-PSMA PET/CT Introduction Prostate specific membrane antigen (PSMA) expression has been demonstrated in tumor neovasculature of many solid tumors, including hepatocellular carcinoma (HCC). The purpose of this study is to evaluate PSMA expression in patients with HCC. Materials and Methods Nineteen HCC patients who underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) as part of restaging procedure also underwent 68Ga-PSMA PET. 18F-FDG PET and 68Ga-PSMA findings were compared visually as well as quantitatively using maximized standardized uptake values (SUVmax). Results FDG was positive in 15 patients while 16 patients demonstrated PSMA expression. The only extrahepatic finding was one metastatic lymph node detected by both tracers. Mean SUVmax of liver lesions on FDG PET/CT was 8.3 ± 2.3 and mean tumor to background ratio was 2.3 ± 1.5. Respective values for 68Ga-PSMA PET/CT were 17.4 ± 9 and 3.3 ± 2.2. On visual and quantitative evaluation uptake was higher with PSMA in nine patients and higher with FDG in four patients. PSMA and FDG activity were similar in three patients. One of the FDG positive patients was PSMA negative whereas two patients were PSMA positive but FDG negative. Heterogeneous uptake pattern was observed in three patients. Comparison of mean SUVmax and T/B values between PET studies revealed no statistically significant difference (P > 0.1). The mean survival was 25 months (range: 18–32 months) and SUVmax of PSMA (P = 0.05) and FDG (P = 0.012) showed medium strength of correlation with overall survival. Conclusion PSMA expression in advanced HCC can be demonstrated by 68Ga-PSMA PET but is not superior to FDG PET however it could be useful for identifying patients with limited therapeutic options.

Decreased Striatal Vesicular Monoamine Transporter Type 2 Correlates With the Nonmotor Symptoms in Parkinson Disease Objective Nonmotor symptoms (NMS) are critical players in the patients' quality of life in Parkinson disease (PD). Vesicular monoamine transporter type 2 (VMAT2) has been reported owing to a role in affecting dopamine neurons in the striatum. Therefore, this study set out to characterize the relationship between VMAT2 distribution in the striatum in relation to the NMS in PD. Methods Totally, 21 age-matched normal controls and 37 patients with PD in the moderate stages were included, followed by examination using 18F-DTBZ (18F-AV133) PET/CT. The specific uptake ratio (SUR) of each striatal subregion was then determined with the occipital cortex as the reference background region. The overall NMSs of each individual patient were evaluated. Finally, the role of the striatal SURs in the clinical symptom scores were evaluated through the application of a Spearman correlation analysis as well as a multivariable stepwise regression analysis. Results Patients with PD, particularly those at a more advanced stage, exhibited a more pronounced reduction in SURs in the bilateral putamen and caudate nucleus (P < 0.05, vs healthy controls). Meanwhile, patients at more advanced PD stages were found to have significantly worse scores in NMS except cognitive function. The Spearman correlation analysis demonstrated that NMS scores, with the exception of cognition scores, were correlated with striatal SURs (P < 0.05). Conclusion The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.

Risk Factors for Indeterminate Response After Radioactive Iodine Therapy in Patients With Differentiated Thyroid Cancer Purpose We investigated the risk factors of indeterminate response (IDR) in patients who underwent recombinant human thyroid-stimulating hormone (rhTSH)–aided radioactive iodine therapy (RAIT). Methods A total of 128 patients with papillary thyroid cancer were included in this retrospective study. The patients were classified into excellent response and IDR groups based on follow-up diagnostic whole-body scintigraphy (WBS) and TSH-stimulated thyroglobulin (Tg). Indeterminate response was defined as the presence of a faint uptake in the thyroid bed on the diagnostic WBS or a TSH-stimulated Tg detectable, but less than 10 ng/mL. Parameters that act as significant risk factors for IDR, including age, sex, stage, surgeon, time interval between surgery and RAIT, post-treatment WBS finding, urine iodine-to-creatinine ratio, TSH-unstimulated Tg, and rhTSH-stimulated Tg, were analyzed using a Cox proportional hazards regression method. Results After treatment, 64 patients showed IDR. Recombinant human TSH–stimulated Tg was the only independent risk factor for predicting IDR. Patients with an rhTSH-stimulated Tg greater than 2 ng/mL prior to RAIT were 3.75 times more likely (95% confidence interval, 1.61–8.72) to have an IDR than those with a lower rhTSH-stimulated Tg (≤2 ng/mL). Conclusions Pre-RAIT TSH-stimulated Tg levels are a risk factor for IDR after RAIT.

Efficacy of 177Lu Peptide Receptor Radionuclide Therapy for the Treatment of Neuroendocrine Tumors: A Meta-analysis Objective The purpose of this study was to assess the efficacy of 177Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors. Methods MEDLINE, EMBASE, and Ovid were systematically searched with keywords “lutetium,” “Lu-177,” “PRRT,” “neuroendocrine,” and “prognosis.” Studies evaluating treatment with 177Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 or 1.1, modified RECIST, Southwest Oncology Group (SWOG), or modified SWOG criteria. Pooled proportions of disease response and control rates were calculated for both fixed- and random-effects models. Results Eighteen studies with 1920 patients were included (11 with 1268 patients using RECIST and 6 with 804 patients using SWOG). By RECIST criteria, the pooled disease response rate by random-effects model was 29.1% (95% confidence interval [CI], 20.2%–38.9%), and disease control rate was 74.1% (95% CI, 67.8%–80.0%). By SWOG criteria, the pooled disease response rate by random-effects model was 30.6% (95% CI, 20.7%–41.5%), and disease control rate was 81.1% (95% CI, 76.4%–85.4%). Conclusions Induction therapy, typically 4 treatments, with 177Lu PRRT is an effective method of treating unresectable metastatic neuroendocrine tumors with significant disease response and control rates.

Quality and Safety in Health Care, Part LI: Engagement and Burnout Engagement has 3 different components, the most important of which are felt by some to be vigor and dedication. The third component is absorption. Engagement is considered by some to be the opposite of burnout, although others consider these terms to be not quite opposite, but nearly so. Engaged physicians have greater job satisfaction and less burnout and are less likely to leave their job than physicians who are not engaged. Those physicians who are engaged in their work tend to render patient care that is not only more efficient but also has a higher degree of quality and safety.

Recovery of Renal Function Under PSMA Mediated Radioligand Therapy of Advanced Metastasized Castration Resistant Prostate Cancer Radioligand therapy targeting prostate specific membrane antigen (PSMA-RLT) is becoming increasingly important in palliative care of metastasized castration resistant prostate cancer (mCRPC) as a highly effective and low toxicity therapy option. In addition to its overexpression in prostate cancer cells, PSMA is also physiologically expressed in the kidneys which is raising concerns over dose related nephrotoxicity of PSMA-RLT. We describe potential positive short-term effects of PSMA-RLT on renal function with marked recovery of a pretreatment compromised kidney.

Unexpected Lymphatic Drainage of the Treated Breast This case highlights the use of lymphoscintigraphy with SPECT/CT in patients with previous chest and/or axillary surgery. A 67-year-old woman with a history of left breast carcinoma treated with lumpectomy and radiotherapy, and a second lumpectomy of the ipsilateral breast for a second breast carcinoma, underwent a lymphoscintigraphy for a new left breast lesion. Planar images visualized an alternative lymphatic drainage to the contralateral axilla and to the left paravertebral area. SPECT/CT confirmed sentinel nodes in both stations.

High-Resolution PET Cisternography With 64Cu-DOTA for CSF Leak Detection Intracranial hypotension may lead to chronic, debilitating symptoms, and severe complications. The underlying CSF leak may be difficult to localize. To establish a new diagnostic option for the detection of CSF leaks, 64Cu-DOTA was developed as a tracer for PET imaging. PET/CT imaging was possible with high resolution and without complications. In one patient, the exact site of a dural tear was identified, enabling successful surgical treatment. PET cisternography with 64Cu-DOTA appears to be safe and able to locate a CSF leak. It has the potential to be a problem-solving modality in cases with inconclusive CT, MR, and/or scintigraphic findings.