The purpose of this study was to examine how the introduction of ibuprofen (IBU) affected tumor-targeting and biodistribution properties of 177Lu-labeled IBU-conjugated alpha-melanocyte-stimulating hormone peptides. The IBU was used as an albumin binder and conjugated to the DOTA-Lys moiety without or with a linker to yield DOTA-Lys(IBU)-GG-Nle-CycMSHhex {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Lys(IBU)-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex peptides. Their melanocortin-receptor 1 (MC1R) binding affinities were determined on B16/F10 melanoma cells first. Then the biodistribution of 177Lu-labeled peptides was determined on B16/F10 melanoma-bearing C57 mice at 2 h postinjection to choose the lead peptide for further examination. The full biodistribution and melanoma imaging properties of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex were further evaluated using B16/F10 melanoma-bearing C57 mice. DOTA-Lys(IBU)-GG-Nle-CycMSHhex, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex displayed the IC50 values of 1.41 ± 0.37, 1.52 ± 0.08, 0.03 ± 0.01, and 0.58 ± 0.06 nM on B16/F10 melanoma cells, respectively. 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex exhibited the lowest liver and kidney uptake among all four designed 177Lu peptides. Therefore, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was further evaluated for its full biodistribution and melanoma imaging properties. The B16/F10 melanoma uptake of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was 19.5 ± 3.12, 24.12 ± 3.35, 23.85 ± 2.08, and 10.80 ± 2.89% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Moreover, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex could clearly visualize the B16/F10 melanoma lesions at 2 h postinjection. The conjugation of IBU with or without a linker to GGNle-CycMSHhex affected the MC1R binding affinities of the designed peptides. The charge of the linker played a key role in the liver and kidney uptake of 177Lu-Asp-IBU, 177Lu-Asn-IBU, and 177Lu-Dab-IBU. 177Lu-Asp-IBU exhibited higher tumor/liver and tumor/kidney uptake ratios than those of 177Lu-Asn-IBU and 177Lu-Dab-IBU, underscoring its potential evaluation for melanoma therapy in the future.

PURPOSE Traditional methods of evaluating cardiotoxicity focus on radiation doses to the heart. Functional imaging has the potential to provide improved prediction for cardiotoxicity for patients with lung cancer. Fluorine-18 (18F) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging is routinely obtained in a standard cancer staging workup. This work aimed to develop a radiomics model predicting clinical cardiac assessment using 18F-FDG PET/CT scans before thoracic radiation therapy. METHODS Pretreatment 18F-FDG PET/CT scans from three study populations (N = 100, N = 39, N = 70) were used, comprising two single-institutional protocols and one publicly available data set. A clinician (V.J.) classified the PET/CT scans per clinical cardiac guidelines as no uptake, diffuse uptake, or focal uptake. The heart was delineated, and 210 novel functional radiomics features were selected to classify cardiac FDG uptake patterns. Training data were divided into training (80%)/validation (20%) sets. Feature reduction was performed using the Wilcoxon test, hierarchical clustering, and recursive feature elimination. Ten-fold cross-validation was carried out for training, and the accuracy of the models to predict clinical cardiac assessment was reported. RESULTS From 202 of 209 scans, cardiac FDG uptake was scored as no uptake (39.6%), diffuse uptake (25.3%), and focal uptake (35.1%), respectively. Sixty-two independent radiomics features were reduced to nine clinically pertinent features. The best model showed 93% predictive accuracy in the training data set and 80% and 92% predictive accuracy in two external validation data sets. CONCLUSION This work used an extensive patient data set to develop a functional cardiac radiomic model from standard-of-care 18F-FDG PET/CT scans, showing good predictive accuracy. The radiomics model has the potential to provide an automated method to predict existing cardiac conditions and provide an early functional biomarker to identify patients at risk of developing cardiac complications after radiotherapy.

Lung cancer is the leading cause of cancer death within the United States, yet prior studies have shown a lack of adherence to imaging and treatment guidelines in patients with lung cancer. This study eval-uated the use of 18F-FDG PET/CT imaging before subsequent radia-tion therapy (RT) in patients with non-small cell lung cancer (NSCLC), as recommended by National Comprehensive Cancer Network guide-lines, and whether the use of this imaging modality impacts cancer -specific survival. Methods: This was a retrospective study of the National Cancer Institute's Surveillance, Epidemiology, and End Results program of Medicare-linked data in patients with NSCLC. Hazard ratios and 95% CIs for overall and cancer-specific survival were estimated for patients diagnosed between 2006 and 2015 who underwent either 18F-FDG PET/CT-based or CT-based imaging before subsequent RT. Results: Significant improvement in cancer -specific survival was found in patients who underwent 18F-FDG PET/ CT imaging before subsequent RT, compared with those who under-went CT (hazard ratio, 1.43 [95% CI, 1.32-1.55; P , 0.0001]). Although the National Comprehensive Cancer Network recommends 18F-FDG PET/CT before subsequent RT, 43.6% of patients were imaged with CT alone. Conclusion: Many patients with NSCLC are not being imaged according to national guidelines before subsequent RT, and this omission is associated with a lower cancer-specific survival.

Fever of unknown origin (FUO) is a diagnostic challenge, with its cause remaining undiagnosed in approximately half of patients. Nuclear medicine tests typically are performed after a negative or inconclusive initial workup. Gallium-67 citrate and labeled leukocytes were previous mainstays of radionuclide imaging for FUO, although they had limited diagnostic performance. FDG PET/CT has subsequently emerged as the nuclear medicine imaging test of choice, supported by a growing volume of evidence. A positive FDG PET/CT result contributes useful information by identifying potential causes of fever, localizing sites for further evaluation, and guiding further management; a negative result contributes useful information by excluding focal disease as the cause of fever and predicts a favorable prognosis. In 2021, CMS rescinded a prior national noncoverage determination for FDG PET for infection and inflammation, leading to increasing national utilization of FDG PET/CT for FUO workup. This article reviews the current status of the role of FDG PET/CT in the evaluation of patients with FUO. The literature reporting the diagnostic performance and yield of FDG PET/CT in FUO workup is summarized, with comparison with historically used nuclear medicine tests included. Attention is also given to the test's clinical impact; protocol, cost, and radiation considerations; and application in children.

Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we review the role of SSTR PET scan in the management of NETs, including the indications for the scan, pitfalls in interpretation, and imaging selection criteria for peptide receptor radionuclide therapy. We also discuss the complementary role of fluorodeoxyglucose PET particularly for patients with high-grade disease.

PURPOSE:Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis. METHODS AND MATERIALS:Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy. RESULTS:Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria. CONCLUSIONS:4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.

OBJECTIVE:Current ventilation and perfusion dose-response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose-responses among lung cancer patients treated with radiotherapy.METHODS:20 patients enrolled on a prospective functional avoidance protocol underwent single photon emission computed tomography-CT ventilation and perfusion scans pre- and post-radiotherapy. Relative changes in pre- to post-treatment ventilation and perfusion in lung regions receiving ≥20 Gy were calculated. In addition, the slopes of the linear fit to the relative ventilation and perfusion changes in regions receiving 0-60 Gy were calculated. A radiologist read and assigned a functional defect score to pre- and post-treatment ventilation/perfusion scans.RESULTS:25% of patients had a difference >35% between ventilation and perfusion pre- to post-treatment changes and 20-30% of patients had opposite directions for ventilation and perfusion pre- to post-treatment changes. Using a semi-quantitative scale, radiologist assessment showed that 20% of patients had different pre- to post-treatment ventilation changes when compared to pre- to post-treatment perfusion changes.CONCLUSION:Our data showed that ventilation dose-response can differ from perfusion dose-response for 20-30% of patients. Therefore, when performing thoracic dose-response in cancer patients, it is insufficient to look at ventilation or perfusion alone; but rather both modes of functional imaging may be needed when predicting for clinical outcomes.ADVANCES IN KNOWLEDGE:The significance of this study can be highlighted by the differences between the intrapatient dose-response assessments of this analysis compared to existing population-based dose-response analyses. Elucidating intrapatient ventilation and perfusion dose-response differences may be valuable in predicting pulmonary toxicity in lung cancer patients post-radiotherapy.

This study investigates agreement between ventilation and perfusion for lung cancer patients undergoing radiotherapy. Ventilation-perfusion scans of nineteen patients with stage III lung cancer from a prospective protocol were compared using voxel-wise Spearman correlation-coefficients. The presented results show in about 25% of patients, ventilation and perfusion exhibit lower agreement.

Fever of unknown origin (FUO) is a condition with high mortality that often presents a diagnostic challenge to clinicians. We present the case of a patient with FUO who was discovered to have a rare mycotic aneurysm of the thoracic aorta by 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Mycotic aneurysm, also known as an infected aneurysm, is a highly lethal condition due to the risk of sepsis and aneurysmal rupture. While unusual to present in this manner, it is of utmost importance to promptly recognize a mycotic aneurysm as a potential diagnosis because initiation of treatment is critical in reversing the natural history of the disease.

Purpose/Objective(s)Pulmonary toxicity, and in particular radiation pneumonitis, remains a major limitation in the radiotherapy treatment of lung cancer patients. Functional avoidance radiotherapy proposes to use functional imaging to reduce pulmonary toxicity by designing radiotherapy treatment plans that reduce doses to functional regions of the lung. A novel form of lung functional imaging has been proposed that uses 4DCT imaging to calculating 4DCT-based lung ventilation (4DCT-ventilation) maps. A phase II, multi-center, prospective study was initiated to evaluate 4DCT-ventilaiton functional avoidance radiotherapy. The study hypothesis was that functional avoidance radiotherapy could reduce the rate of ≥ grade 2 radiation pneumonitis to 12% compared to a 25% ≥ grade 2 historical pneumonitis rate. Based on a binomial, one-sided 95% confidence interval (CI), the trial would be positive if ≤ 11 of 67 patients (16.4%) experienced ≥ grade 2 radiation pneumonitis.Materials/MethodsLung cancer patients receiving curative intent radiotherapy (prescription doses of 45-75 Gy) and planned curative intent chemotherapy were accrued from 2 institutions. Patient 4DCTs along with image processing techniques were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose and respecting tolerances of organs-at-risk. Functional doses were reduced by selecting favorable arc geometry and employing optimization techniques. Patients were evaluated for pneumonitis at 3, 6, and 12 months after completing radiotherapy.ResultsSixty-seven evaluable patients were accrued between April 2015 and December 2019. Median Karnofsky performance status was 90 and 76% of patient's had stage III disease. The median prescription dose was 60 Gy (range 45–66 Gy) delivered in 30 fractions (range 15–33 fractions). Eleven patients (16%) underwent surgery as part of their treatment, 88% of patients received concurrent chemotherapy, and 25% of patients were treated with immunotherapy while they were on study. Median follow-up was 312 days. The crude rate of ≥ grade 2 radiation pneumonitis was 14.9% (10/67 patients, upper 95% CI of 24.0%), meeting the phase II criteria.ConclusionBecause 4DCTs are a standard part of the treatment planning process for lung cancer patients, 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra imaging procedure necessary. Our study reports on the first multi-center, prospective study of 4DCT-ventilation functional avoidance radiotherapy. The study met phase II criteria demonstrating reduced pneumonitis rates and provides favorable evidence for 4DCT-ventilation functional avoidance to be investigated in a phase III study. Future work will report on secondary objective including pulmonary function, patient-reported outcomes, and imaging-based end-points.

KMT2B-related dystonia (DYT-28) is a recently identified autosomal-dominant disorder caused by mutations in the KMT2B gene.1, 2 KMT2B encodes a histone lysine methyltransferase, which plays a central role in regulating gene expression through epigenetic modifications.3 The disorder is characterized by childhood-onset and progressive dystonia, commonly starting in the limbs with subsequent cervical, oromandibular and laryngeal involvement. The clinical phenotype further includes bulbar symptoms manifesting as dysarthria and dysphagia, developmental delay and dysmorphic features. We present a case of DYT-28 caused by a novel KMT2B mutation, initially with characteristic clinical features, who in early adulthood developed prominent parkinsonism, good response to dopaminergic therapy, and positive pre-synaptic dopamine transporter (DaT) SPECT imaging. A 33-year-old right-handed Caucasian male presented to our clinic for progressively worsening generalized dystonia. He had no history of birth trauma, toxin exposure or family history of dystonia, though his paternal grandfather developed parkinsonism and dementia in his 70s. His initial neurological symptom was right foot supination at age 3. At age 4, delays in verbal milestones were noted. Dystonia slowly progressed, involving his right upper extremity at age 6 and his neck and trunk at age 17. Trihexiphenidyl, lorazepam and botulinum toxin injections were trialed, but only trihexiphenidyl provided benefit. MRI brain was normal and genetic testing (ataxia panel and chromosomal microarray) were negative. At age 23 bilateral globus pallidus interna deep brain stimulation (DBS) surgery was performed, resulting in significant improvement in dystonia, particularly in his upper body and trunk. Our initial clinical evaluation noted dysmorphic features (broad nasal bridge, elongated face and low set ears), a nasal and dysarthric voice, generalized dystonia, elevation of the right shoulder and parkinsonism with rigidity, bradykinesia (left greater than right) and freezing of gait (FOG) with a MDS-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS) of 48 (Video 1). Extensive DBS reprogramming, including turning off the DBS, testing modifiable parameters and performing a monopolar review, was performed to ensure his parkinsonian symptoms were not stimulation-induced.4 A comprehensive dystonia panel from MNG Laboratories (NextGen Sequencing Panel and Copy Number Analysis; 192 Genes and mtDNA and HTT Repeat Expansion Analysis) and a DaT scan were acquired. Genetic testing identified a presumed de novo six-nucleotide deletion of KMT2B, introducing a premature stop codon (c.974_979del, p.Ser325Ter). The DaT scan revealed decreased uptake in the right greater than left putamen (Fig. 1). We also obtained a Hereditary Parkinson's Disease and Parkinsonism panel from Invitae Laboratories, which was negative. Carbidopa/levodopa up-titrated to 1 tablet (25 mg/100 mg) three times daily improved gait and parkinsonism. Further dosage increases worsened FOG and subsequently carbidopa/levodopa was discontinued. The patient transitioned to rotigotine, and at 4 mg gait significantly improved without worsening of FOG. Eight months later he continued to receive benefit from rotigotine with a MDS-UPDRS of 36 and significant improvement in his gait. Parkinsonism is a rarely cited feature of KMT2B-related dystonia,3, 5 and FOG has not previously been reported in the literature. Our patient's initial clinical course was consistent with prior KMT2B cases reported in the literature. Unusual, however, was the development of parkinsonism and FOG in his 30s. Even more distinct were his positive DaT scan and responsiveness to dopaminergic therapy.2, 3 All DaT scans thus far reported in KMT2B patients (three cases) showed normal radiotracer uptake.2 The etiology of our patient's suspected nigrostriatal degeneration is not known, but our patient was imaged at an older age than prior cases. Therefore, other patients may be at risk for dopaminergic neuronal loss as they age. Alternatively, the dopaminergic deficit may be, at least partially, due to our patient's unique KMT2B mutation. Several mutations in the same domain (AT-hook DNA binding domain) have been reported and none with parkinsonism.5 Genotyping of additional cases of DYT-28 with and without accompanying parkinsonism in adulthood will be needed to determine if mutation differences explain the development of parkinsonism and FOG in our patient. Interestingly, KMT2B mutations have been associated with decreased expression of THAP1 and TOR1A, both of which are known to be associated with dysfunctional dopaminergic systems.6 This may provide a link between KMT2B mutations and nigrostriatal degeneration, but the downstream consequences of KMT2B mutations are yet to be elucidated. This case rests in the company of other cases of genetic neurodevelopmental dystonias which have positive DaT scans and are dopamine responsive, including mutations in NR4A2,7 SPG118 and ACTB (p.Arg183Trp).9 Our case has important clinical implications. First, it will be important for clinicians caring for these patients to evaluate them for development of parkinsonism as these symptoms may be responsive to dopaminergic medication. Second, it highlights the need to potentially expand the phenotypic expression of KMT2B mutations especially in later stages of the disease. Third, it underscores the importance of ongoing mechanistic research which will elucidate the pathophysiology of DYT-28, and potentially other not yet identified causes of dystonia and parkinsonism, given the post-translational role of KMT2B. In summary, we report a new KMT2B mutation identified in a male with childhood-onset progressive generalized dystonia who developed parkinsonism and FOG in his 30s and was found to have an abnormal DaT scan and clinical response to dopaminergic medication. This is the first report of dopa-responsive parkinsonism and FOG accompanied by evidence of dopaminergic degeneration in a patient with DYT-28. Thank you to Jean Jirikowic, MSGC, for her help with this case. (1) Manuscript Preparation: A. Writing of first draft, B. Review and critique J.F.: 1A, 1B J.K.: 1B M.T.: 1B B.B.: 1A, 1B Ethical Compliance Statement: Ethical guidelines were followed in the absence of an IRB. Written patient consent was obtained. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest. Financial Disclosures for the Previous 12 Months: Dr. Brian D. Berman has the following disclosures to report: Employed by Virginia Commonwealth University and MCV Foundation; consultant for International Parkinson and Movement Disorder Society and the National Football League Players Association; medical advisory board member for the Benign Essential Blepharospasm Research Foundation and the National Spasmodic Torticollis Association and member of the American Academy of Neurology Clinical Research Subcommittee; and has received research grant support from the Parkinson's Foundation, Dystonia Coalition (receives the majority of its support through NIH grant NS065701 from the Office of Rare Diseases Research in the National Center for Advancing Translational Science and National Institute of Neurological Disorders and Stroke), Colorado Clinical and Translational Science Institute, Benign Essential Blepharospasm Research Foundation, and Tools4Patient. The authors declare that there are no additional disclosures to report.

OBJECTIVE Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment. METHODS A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure. RESULTS RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002). CONCLUSION More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.

PURPOSE:Studies have noted a link between radiation dose to the heart and overall survival (OS) for patients with lung cancer treated with chemoradiation. The purpose of this study was to characterize pre- to posttreatment cardiac metabolic changes using fluorodeoxyglucose/positron emission tomography (FDG-PET) images and to evaluate whether changes in cardiac metabolism predict for OS.METHODS AND MATERIALS:Thirty-nine patients enrolled in a functional avoidance prospective study who had undergone pre- and postchemoradiation FDG-PET imaging were evaluated. For each patient, the pretreatment and posttreatment PET/CTs were rigidly registered to the planning CT, dose, and structure set. PET-based metabolic dose-response was assessed by comparing pretreatment to posttreatment mean standardized uptake values (SUVmean) in the heart as a function of dose-bin. OS analysis was performed by comparing SUVmean changes for patients who were alive or had died at last follow-up and by using a multivariate model to assess whether pre- to posttreatment SUVmean changes were a predictor of OS.RESULTS:The dose-response curve revealed increasing changes in SUV as a function of cardiac dose with an average SUVmean increase of 1.7% per 10 Gy. Patients were followed for a median of 437 days (range, 201-1131 days). SUVmean change was significantly predictive of OS on multivariate analysis with a hazard ratio of 0.541 (95% confidence intervals, 0.312-0.937). Patients alive at follow-up had an average increase of 17.2% in cardiac SUVmean while patients that died had an average decrease in SUVmean decrease of 13.5% (P = .048).CONCLUSIONS:Our data demonstrated that posttreatment SUV changes in the heart were significant indicators of dose-response and predictors of OS. The present work is hypothesis generating and must be validated in an independent cohort. If validated, our data show the potential for cardiac metabolic changes to be an early predictor for clinical outcomes.

PURPOSE:To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma.METHODS:We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated.RESULTS:One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes.CONCLUSION:Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

To assess postbiopsy pigmentation (PBP) as a prognostic feature in patients with cutaneous head and neck (H&N) melanoma.

Background Patients with scalp melanoma have poor oncologic outcomes compared with those with other cutaneous sites. Sentinel lymph node (SLN) biopsy provides prognostic information but is challenging in the head and neck. We explore the anatomic distribution of scalp melanoma and describe the most common sites of SLN drainage and of SLN metastatic disease. Methods Retrospective review of scalp melanoma patients who underwent SLN biopsy. Melanoma location was classified as frontal, coronal apex, coronal temporal, or posterior scalp. SLN location was classified by lymph node level and region. Results We identified 128 patients with scalp melanoma. The most common primary tumor location was the posterior scalp (43%) and the most frequent SLN drainage site was the level 2 lymph node basin (48%). Total 31 patients (24%) had metastatic disease in an SLN. Scalp SLNs, classified as being in the posterior auricular or occipital region, were localized in 26% of patients. For patients in which a scalp SLN was identified, 30% had a positive scalp SLN (n = 10). Conclusions Scalp SLNs are frequent drainage sites for scalp melanoma and, when found, have a 30% chance of harboring metastatic disease. Surgeons, radiologists, and pathologists should be vigilant in identifying, removing, and analyzing scalp SLNs.

e16551 Background: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) is a widely-used imaging modality for many cancers; however, its utility in prostate cancer is limited. Fatty acid oxidation (FAO) is a primary source of energy for early prostate cancer. We previously demonstrated that FAO inhibition in prostate cancer mouse models resulted in increased glucose metabolism and enhanced tumor FDG uptake, with peak uptake at 24 hours. To validate these preclinical findings, we conducted a pilot study to evaluate whether a partial FAO inhibitor, ranolazine, increases tumor FDG uptake on PET imaging for prostate cancer. Methods: Prostate cancer patients with untreated localized cancer (arm 1) and with metastatic disease on hormonal or other therapy (arm 2) were enrolled and underwent baseline and post-treatment FDG-PET/CT scans (standard dose of 10 mCi FDG). Ranolazine 1000mg PO BID x 2 doses was given within 24-48 hours of the second scan. The primary objective was to evaluate the rate of successful enhancement of FDG uptake on PET imaging, based on one or more of the following criteria: 30% increase in maximum SUV with an absolute change of 2 units; 30% increase in mean SUV with an absolute change of 0.75 units; or 20% increase in mean SUV with an absolute change of 1 unit. Results: Eleven patients (four in arm 1, seven in arm 2) were enrolled. Ranolazine was well tolerated by all participants, with no adverse effects observed. Both increases and decreases in SUV uptake were observed on the post-ranolazine scans. No patient met the predefined criteria for successful enhancement of FDG uptake. There was an incidental finding of thyroid cancer seen in one patient that was discovered on PET imaging. The study was closed early due to the emerging clinical availability of alternative and effective PET imaging modalities such as [11C] choline, [18F] fluciclovine, [68Ga] PSMA, and [18F] sodium fluoride. Conclusions: Given the small sample size, we were not able to make any firm conclusions. In this limited study, ranolazine treatment did not result in enhanced FDG-PET-tumor detection. ClinicalTrials.gov identifier: NCT01992016. Supported by the William Meyn Foundation; NIH/NCI P30CA46934, 5K12CA086913, CA168934; ACS RSG-16-256-01-TBE; Colorado Translational Research Imaging Center Pilot Award; Paul Sandoval Cancer Research Summer Fellowship. Clinical trial information: NCT01992016.

The importance of the heart has been emphasized in recent thoracic chemo-radiation (CRT) literature. A lung cancer dose escalation study (RTOG 0617) noted that heart doses were significantly associated with overall survival (OS). The purpose of this study was to characterize pre-to-post treatment cardiac metabolic changes using FDG-PET scans and to evaluate whether PET-based cardiac imaging changes predicted for OS. Lung cancer patients enrolled on a multi-institutional, prospective clinical trial for functional avoidance thoracic radiotherapy were analyzed. 39 patients who had undergone pre and post chemo-radiation FDG-PET imaging were studied. Post-CRT PET scans were acquired at a median time of 97 days (range 11 to 477 days) after treatment. Patients on the study were treated with definitive CRT with radiation doses ranging from 45-60 Gy in 15-30 fractions. For each patient, the pre-treatment PET-CT and post-treatment PET-CT were rigidly registered to the planning CT, dose, and structure set. PET-based dose-response was assessed by comparing pre-treatment to post-treatment Standardized Uptake Values (SUV) in the heart contour. A dose-response curve was generated by binning each voxel in the heart contour into 10 Gy dose-bins and analyzing the average SUV changes in each dose-bin. Patients on the study were followed for OS for up to 14 months after completing chemo-radiation. We evaluated whether the pre-to-post treatment changes in the average or maximum SUV were predictive of OS. The OS analysis was performed by comparing mean SUV changes for patients that were alive or had died at last follow-up and by using a univariate cox proportional hazard model to assess whether pre-to-post treatment SUV changes were a significant predictor of OS. The cardiac SUV dose-response curve revealed increasing changes in SUV as a function of dose with relative SUV increases of 11.4%, 9.8%, 9.4%, 12.2%, 14.2%, and 20.1% in the 10, 20, 30, 40, 50, and 60 Gy dose-bins, respectively. The SUV dose-response curve demonstrated an average increase of 1.7% for every 10 Gy. Median follow-up was 410 days (range 181 to 541) with 30/39 patients alive at last follow-up. Patients that were alive at follow up had an average increase of +17.2% in cardiac SUV while patients that did not survive had a decrease in SUV of -13.5% (p=0.048). Both the mean and maximum pre to post-treatment SUV changes were significant predictors (p<0.03) of OS. Functional imaging has been used for target delineation and evaluating normal lung function in thoracic CRT but has yet to be used for cardiac treatment response assessment. In our dataset, post-treatment changes in cardiac PET were significant indicators of dose-response and potential predictors of OS. Pre and post-treatment PET imaging is frequently obtained for lung cancer patients and if validated by multivariate analysis, our data show the potential for PET cardiac changes to be an early predictor for cardiac death, allowing for intervention.

INTRODUCTION:Scintigraphic evaluation of the thyroid gland enables determination of the iodine-123 iodide or the 99mTc-pertechnetate uptake and distribution and remains the most accurate method for the diagnosis and quantification of thyroid autonomy and the detection of ectopic thyroid tissue. In addition, thyroid scintigraphy and radioiodine uptake test are useful to discriminate hyperthyroidism from destructive thyrotoxicosis and iodine-induced hyperthyroidism, respectively.METHODS:Several radiopharmaceuticals are available to help in differentiating benign from malignant cytologically indeterminate thyroid nodules and for supporting clinical decision-making. This joint practice guideline/procedure standard from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides recommendations based on the available evidence in the literature.CONCLUSION:The purpose of this practice guideline/procedure standard is to assist imaging specialists and clinicians in recommending, performing, and interpreting the results of thyroid scintigraphy (including positron emission tomography) with various radiopharmaceuticals and radioiodine uptake test in patients with different thyroid diseases.