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Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with 99mTc-labeled carbon nanoparticles (99mTc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of 99mTc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of 99mTc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The 99mTc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where 99mTc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of 99mTc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism.

Our article addresses the prevailing trend of new terminology introduced alongside the progress being made in nuclear medicine. Our article provides a historic, current, and future perspective.

The novel coronavirus 2 pandemic is causing widespread disruption in everyday life necessitating urgent and radical adaptations in operating procedures at nuclear medicine facilities. The potential for causing severe illness, COVID-19, calls for strict observance of preventive measures aimed to mitigate the spread of the virus. The threat of COVID-19 is particularly serious as there is no vaccine and no specific antiviral therapy. Further complications are introduced by shortages of personal protective equipment for healthcare workers who have direct contact with patients and effective testing to identify infected patients, raising the need for delaying some testing and therapies. Certain vulnerable segments of the general population have been identified (advanced age and certain comorbidities), which should heighten further their preventive efforts. Therefore, this guidance is intended to be operationalized depending on a facility’s specific needs and local disease prevalence.

Purpose: The aim of this study was to assess the potential role of thyroglobulin (Tg) kinetics in predicting 2-[18F]-FDG-PET/CT results and overall survival (OS) in patients affected by differentiated thyroid carcinoma (DTC) and suspected recurrence. Methods: On hundred and thirty-nine patients were retrospectively included. All patients underwent 2-[18F]-FDG-PET/CT due to detectable Tg levels and negative [131I] whole-body scan. The last two consecutive serum Tg measurements before PET/CT were used for Tg-doubling time (TgDT) and Tg-velocity (Tg-vel) calculation. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for Tg, TgDT and Tg-vel for predicting PET/CT results. Results: One hundred and fifteen (83%) patients had positive PET/CT for DTC recurrence, while the remaining 24 (17%) negative. Stimulated Tg before PET and Tg-vel were significantly higher in patients with a positive PET/CT scan than negative scan (average Tg 190 vs 14 ng/mL, p= 0.006; average Tg-vel 4.2 vs 1.7 ng/mL/y, p< 0.001). Instead, TgDT was significantly shorter in positive scan (average TgDT 1.4 vs 4.4 years, p< 0.001). ROC curve analysis revealed the best Tg, TgDT and Tg-vel cutoff of 18 ng/mL,1.36 years and 1.95 ng/mL/y. In patients with Tg<18 ng/mL, the PET/CT detection rate was significantly lower in patients with low Tg-vel (p= 0.018) and with long TgDT (p= 0.001). ATA class risk, PET/CT results and Tg before PET were confirmed to be independent prognostic variables for OS. Conclusions: Tg kinetics may help to predict 2-[18F]-FDG-PET/CT results in DTC patients with negative [131I]WBS and detectable Tg, especially in case of low-moderate Tg.

Objectives: The 2015 American Thyroid Association (ATA) guidelines called for significantly more selective 131I therapy in patients with low-risk differentiated thyroid cancer (DTC). We hypothesized that application of these guidelines would significantly reduce the 131I activity utilized by an academic tertiary hospital in Jordan. Methods: All DTC patients managed at Jordan University Hospital (JUH) between 1/2009 and 6/2019 were classified according to the 2015 ATA risk category and 131I activity was assigned accordingly. The actual 131I activity administered was compared with that recommended by the 2015 ATA guidelines. Results: In total, 135/182 DTC patients (74.2%) managed at JUH underwent 131I therapy. Of those, 58 (43%) had ATA low-, 58 (43%) intermediate-, and 19 (14%) high-risk disease. The low-, intermediate-, and high-risk DTC patients received an average (±SD) initial 131I activity of 3.53 ± 0.95, 4.40 ± 1.49, and 5.06 ± 2.52 GBq, respectively. Withholding 131I therapy altogether in the 2015 ATA low-risk patients would result in decreasing the 131I activity in the overall patient population by 37%. Withholding 131I therapy only in low-risk papillary thyroid microcarcinomas while administering 1.11 GBq of 131I to other low-risk patients would result in 28% reduction of 131I. Conclusion: This study demonstrates a significant reduction in 131I therapeutic activity that would be given to DTC patients in an academic tertiary setting in Jordan, following acceptance of the 2015 ATA recommendations. Institutions that adopted the 2015 ATA guidance should measure outcomes in comparison to their historical controls and report those findings, while long-term results of randomized controlled trials are forthcoming.

This review of radioactive iodide treatment (RAIT) extends from historical origins to its modern utilization in differentiated thyroid cancer (DTC). The principles embedded in the radiotheragnostics (RTGs) paradigm are detailed. The diverse approaches in current practice are addressed, and this broad variability represents a major weakness that erodes our specialty’s trust-based relationship with patients and referring physicians. The currently developing inter-specialty collaboration should be hailed as a positive change. It promises to clarify the target-based terminology for RAIT. It defines RAIT of post total thyroidectomy (PTT), presumably benign thyroid as ‘remnant ablation’ (RA). ‘Adjuvant treatment’ (AT) referrers to RAIT of suspected microscopic DTC that is inherently occult on diagnostic imaging. RAIT directed at DTC lesion(s) overtly seen on diagnostic imaging is termed ‘treatment of known disease’ (TKD). It was recently recognized that a ‘recurrent’ DTC is actually occult residual DTC in the majority of cases. Thyroglobulin with remnant uptake concord (TRUC) method (aka Tulchinsky method) was developed to validate that a benign remnant in the post-thyroidectomy neck bed, as quantified by the RAI uptake, is concordant with a measured thyroglobulin (Tg) level at the time of the initial post-thyroidectomy evaluation. It allows recognition of occult residual DTC contribution to post-thyroidectomy Tg. Case examples demonstrate the application of the TRUC method for a logical selection of a specific RAIT category, using imaging-guided identification and management of RAI-avid versus RAI-nonavid residual DTC, i.e. the radiotheragnostics paradigm.

IMPORTANCE: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. OBJECTIVE: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18 805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. EXPOSURES: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). MAIN OUTCOMES AND MEASURES: Site-specific and all solid-cancer mortality. RESULTS: A total of 18 805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14 671 [78.0%]), and most had a Graves disease diagnosis (17 615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P = .002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P = .04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P = .01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. CONCLUSIONS AND RELEVANCE: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

The American College of Radiology (ACR) and American College of Nuclear Medicine (ACNM) collaborated to develop a clinical practice document for the performance of fluciclovine positron-emission tomography (PET) / computed tomography (CT) in the evaluation of patients with suspected prostate cancer recurrence based on the elevation of prostate-specific antigen (PSA) level (biochemical recurrence) after prior therapy. Prostate cancer is the third leading cause of cancer death in the United States. Up to 50% of patients diagnosed with prostate cancer will develop biochemical failure after initial therapy. The differentiation of local from extraprostatic recurrence plays a critical role in patient management. The use of functional imaging targeting features of cancer metabolism has proven highly useful in this regard. Amino acid transport is upregulated in prostate cancer. Fluciclovine (anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid, FACBC, Axumin™) is an artificial amino acid PET tracer which demonstrates utility in the diagnosis of recurrent prostate cancer with significant added value to conventional imaging.

Some patients undergoing routine SPECT/CT and PET/CT examinations during the COVID-19 pandemic may incidentally reveal findings of COVID-19–associated pneumonia (C-19AP) on localizing CT. It is critical for nuclear medicine physicians to develop diagnostic skills for timely recognition of typical findings of C-19AP on a localizing CT. Furthermore, it is our responsibility to know the optimal practices for safely isolating and managing such patients while protecting the staff, other patients at the facility, family and/or friend accompanying the patients, and the public in general from risky exposure to COVID-19 sources. We offer several steps following an encounter suspicious of C-19AP.

Intestinal malrotation displays classic pattern of the small bowel activity on hepatobiliary scintigraphy that could lead to the diagnosis, but only if an interpreting physician looks for it. Presented are 2 cases, one demonstrates diagnostic findings during the first 60-minute phase, whereas the other reveals the diagnosis only on the later sincalide stimulation phase. The currently recommended structured reporting for hepatobiliary scintigraphy does not include examination of bowel activity pattern, which could result in a missed diagnosis. Including interrogation of the small bowel pattern into the structured reporting checklist would ensure consistent detection of this rare but most consequential diagnosis.

Significant barriers to informed consent surround the clinical management of adult patients with well-differentiated thyroid cancer. The literature reveals lack of disclosure surrounding clinical equipoise; confusing and conflicting terminology; and an insufficient number of prospective trials with proper ethical oversight. We provide guidance for valid consent to treatment in this population, and propose stipulative definitions for a variety of terms used in this context. Three critical areas are addressed: surgical management, radioactive iodine management and nonvalidated practice. Sound ethical frameworks for valid consent in patients with low-risk thyroid cancer include consent to observational (or ‘active surveillance’) research protocols, consent to nonvalidated practice and consent when there are opposing standards of care due to insufficient data and disagreement among the community of experts.

This US survey aimed to determine (1) relative utilization of the 2 techniques, a gas radiopharmaceutical technique (GRT) versus aerosolized radiopharmaceutical technique (ART), in ventilation-perfusion scintigraphy done for pulmonary embolism indication and (2) radiopharmaceuticals (RFs) used.

The most common cause of acute right lower quadrant (RLQ) pain requiring surgery is acute appendicitis (AA). This narrative’s focus is on imaging procedures in the diagnosis of AA, with consideration of other diseases causing RLQ pain. In general, Computed Tomography (CT) is the most accurate imaging study for evaluating suspected AA and alternative etiologies of RLQ pain. Data favor intravenous contrast use for CT, but the need for enteric contrast when intravenous contrast is used is not strongly favored. Radiation exposure concerns from CT have led to increased investigation in minimizing CT radiation dose while maintaining diagnostic accuracy and in using algorithms with ultrasound as a first imaging examination followed by CT in inconclusive cases. In children, ultrasound is the preferred initial examination, as it is nearly as accurate as CT for the diagnosis of AA in this population and without ionizing radiation exposure. In pregnant women, ultrasound is preferred initially with MRI as a second imaging examination in inconclusive cases, which is the majority.

A 25-year-old man was referred for chronic right upper quadrant abdominal pain for hepatobiliary scintigraphy to evaluate the gallbladder (GB) function. An unexpected GB contraction with ejection fraction (EF) of 90% was observed during the first hour of baseline imaging. Subsequent stimulation with sincalide produced GB EF of 99%. A similar case previously reported also showed normal unexpected GB EF that predicted similar post–sincalide GB EF. These examples support what should be evident: A normal unexpected GB EF is a sufficient evidence for a normal GB function and should obviate need for sincalide stimulation.

Marginal zone lymphoma (MZL) is an indolent B-cell lymphoma arising from marginal zone B-cells present in lymph nodes and extranodal tissues. MZL comprises 5–17% of all non-Hodgkin’s lymphomas in adults. The World Health Organization categorizes MZL into three distinct types based on their site of impact: (1) splenic marginal zone lymphoma (SMZL); (2) nodal marginal zone lymphoma (NMZL); (3) extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, which can be subdivided into gastric and nongastric. The subgroups of MZL share some common features but are different in their biology and behavior. Owing to the rarity of MZL there are few randomized trials available comparing various treatment options and therefore treatment is controversial, lacking standard guidelines. Treatment should be patient tailored and can range from a ‘watchful waiting’ approach for asymptomatic patients without cytopenias to surgery or localized radiation therapy. Rituximab in combination with chemotherapy has resulted in longer failure-free survival than chemotherapy alone in patients with SMZL. Helicobacter pylori positive gastric MALT shows a good response rate to triple antibiotic therapy. Newer therapies such as bendamustine, everolimus, lenalidomide, vorinostat and phosphoinositide 3-kinase inhibitors are in clinical trials for patients with relapsed or refractory MZL and have shown promising results. We are presently conducting clinical trials testing the efficacy of the epigenetic activity of cladribine as a hypomethylating agent in combination with the histone deacetylase inhibitor (HDACi) vorinostat and rituximab in patients with MZL. Further studies with the newer agents should be done both in newly diagnosed or relapsed/refractory MZL to streamline the care and to avoid the use of toxic chemotherapies as initial treatment.

Because acute coronary thrombosis can cause unstable coronary artery disease, fibrinopeptide A, a reliable marker of coagulation activity, may play a role in the evaluation of unstable Ischemic syndromes. A new method of fibrinopeptide A sampling, spot urine normalized to urinary creatinine, was evaluated in patients with stable and unstable angina pectoris and acute myocardial infarction. Serial samples were obtained to characterize the changes in urinary fibrinopeptide A levels over time in patients with Ischemic heart disease.

Recently, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) has been used to image thyroid carcinoma. A prospective study was performed to compare the efficacy of99mTc-MIBI to thallium-201 (201T1) scintigraphy in patients with differentiated thyroid carcinoma. The clinical utility of all radionuclide imaging modalities, i.e.,99mTc-MIBI,201Tl, and iodine-131 Na (131I-Na), as well as serum thyroglobulin estimation, was evaluated. Thirty-four post-thyroidectomy patients (age range: 26–76 years) underwent 45 studies. Histopathologies studied included fourteen papillary, eight papillaryfollicular, ten follicular, one Hürthle cell, and one medullary carcinoma of the thyroid. Following optimal stimulation of endogenous thyroid stimulating hormone (i.e, TSH >-50 mU/ml), the patients underwent201Tl and99mTc-MIBI scintigraphy. Concomitant131I-Na scintigraphy was performed and serum thyroglobulin levels were measured. Sixteen scan sets were performed prior to131I-Na ablation therapy. Twenty-nine scan sets were performed following131I-Na ablation therapy. The presence or absence of thyroid cancer was established by clinical, biochemical, radiologic, and/or biopsy findings. There was no significant difference in sensitivity and specificity of201Tl scintigraphy versus99mTc-MIBI scintigraphy in pre- and postablation studies.131I-Na scintigraphy with determination of thyroglobulin level was sufficient in preablation studies. Among postablation patients, the addition of99mTc-MIBI or201Tl offered a higher diagnostic yield. Between the201Tl and99mTc-MIBI studies, there was a concordance of 69% in preablation and 97% among postablation patients (P=0.027). It is concluded that99mTc-MIBI is a suitable alternative to201Tl scintigraphy in thyroid carcinoma, especially following thyroidectomy and131I-Na therapy.131I-Na scintigraphy with serum thyroglobulin is adequate in both pre- and postablation patients. Among the post-131I-Na ablation patients,99mTc-MIBI or201Tl is extremely valuable for tumor localization, especially when the131I-Na whole-body scan is negative. The combination of99mTc-MIBI or201Tl scintigraphy with131I-Na and serum thyroglobulin offers the highest diagnostic yield.

This pilot study assessed the urinary fibrinopeptide A (uFPA) levels and the combination of uFPA test plus ventilation/perfusion (V/Q) scan in the diagnostic evaluation of acute pulmonary embolism (PE). One hundred consecutive patients were studied prospectively. Twenty-nine patients fulfilled diagnostic criteria defined in this study (seven with and 22 without PE). The uFPA concentration was significantly higher in patients with than without PE (41.1 ± 2.6 vs 4.8 ± 2.5 ng/mg of creatinine, p<0.0001). In all patients with PE, the uFPA levels were higher than threshold value derived by adding 2 standard deviations to the mean uFPA concentration of patients without PE. In patients without PE, the V/Q scan was negative in 16, the uFPA test was negative in 18, and at least one of the tests was negative in 21. These preliminary data suggest that a negative uFPA test may be helpful in excluding PE and that uFPA in combination with V/Q lung scans may correctly exclude PE in more patients than either test alone. Further studies in a large unselected population are needed to confirm these results.

• A patient presented with syncope, and a diagnosis of carotid sinus syndrome was established. Further evaluation revealed a large nasopharyngeal carcinoma invading the left petrous bone. There were no cervical metastases. The tumor partially regressed with radiation therapy, and there was complete resolution of the carotid sinus syndrome, but the patient died three months later of metastatic disease. Autopsy confirmed petrous bone involvement by the mass but no cervical metastatic disease. This Is the first reported case (to our knowledge) of malignancy-associated carotid sinus syndrome attributable to a primary nasopharyngeal carcinoma. The literature on malignancy-associated carotid sinus syndrome Is reviewed, with emphasis on pathophysiology and treatment.(Arch Intern Med 1988;148:1217-1219)

An 82-year-old woman presented for routine follow-up PET/CT after undergoing local melanoma resection in the left lower leg, isolated limb infusion chemotherapy, and immunomodulation therapy with Bacillus Calmette-Guérin (BCG) vaccine. Symmetric, bilateral, moderately intense FDG avid axillary and inguinal cutaneous nodules were observed that were new from the prior PET-CT. The patient had developed skin lesions at the BCG injection sites several months before the study. The case raises awareness to PET/CT appearance of local inflammatory response to BCG injection, which could be mistaken by an unaware reader for recurrent melanoma.