SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE.

Hematologic toxicity, although often transient, is the most common limiting adverse effect during somatostatin peptide receptor radionuclide therapy. This study investigated the association between Monte Carlo-derived absorbed dose to the red marrow (RM) and hematologic toxicity in patients being treated for their neuroendocrine tumors. Methods: Twenty patients each receiving 4 treatment cycles of [177Lu]Lu-DOTATATE were included. Multiple-time-point 177Lu SPECT/CT imaging-based RM dosimetry was performed using an artificial intelligence-driven workflow to segment vertebral spongiosa within the field of view (FOV). This workflow was coupled with an in-house macroscale/microscale Monte Carlo code that incorporates a spongiosa microstructure model. Absorbed dose estimates to RM in lumbar and thoracic vertebrae within the FOV, considered as representations of the whole-body RM absorbed dose, were correlated with hematologic toxicity markers at about 8 wk after each cycle and at 3- and 6-mo follow-up after completion of all cycles. Results: The median of absorbed dose to RM in lumbar and thoracic vertebrae within the FOV (D median,vertebrae) ranged from 0.019 to 0.11 Gy/GBq. The median of cumulative absorbed dose across all 4 cycles was 1.3 Gy (range, 0.6-2.5 Gy). Hematologic toxicity was generally mild, with no grade 2 or higher toxicity for platelets, neutrophils, or hemoglobin. However, there was a decline in blood counts over time, with a fractional value relative to baseline at 6 mo of 74%, 97%, 57%, and 97%, for platelets, neutrophils, lymphocytes, and hemoglobin, respectively. Statistically significant correlations were found between a subset of hematologic toxicity markers and RM absorbed doses, both during treatment and at 3- and 6-mo follow-up. This included a correlation between the platelet count relative to baseline at 6-mo follow up: D median,vertebrae (r = -0.64, P = 0.015), D median,lumbar (r = -0.72, P = 0.0038), D median,thoracic (r = -0.58, P = 0.029), and D average,vertebrae (r = -0.66, P = 0.010), where D median,lumbar and D median,thoracic are median absorbed dose to the RM in the lumbar and thoracic vertebrae, respectively, within the FOV and D average,vertebrae is the mass-weighted average absorbed dose of all vertebrae. Conclusion: This study found a significant correlation between image-derived absorbed dose to the RM and hematologic toxicity, including a relative reduction of platelets at 6-mo follow up. These findings indicate that absorbed dose to the RM can potentially be used to understand and manage hematologic toxicity in peptide receptor radionuclide therapy.

Management of Diabetes Mellitus Before 18F-Fluorodeoxyglucose PET/CT: A Nationwide Patient-Centered Assessment of Approaches to Examination Preparation.

PURPOSE: The aim of this study was to perform, from the patient's point of view, a nationwide assessment of nuclear medicine practices regarding diabetic management before 18F-fluorodeoxyglucose (FDG) PET/CT for oncologic indications. METHODS: This prospective observational study was exempt from institutional review board oversight. Sixty-five nuclear medicine scheduling lines (33 academic, 32 private practice, 12-17 in each of the five US regions) were called using a prewritten script under the guise of a nonexpert patient's family member about scheduling a patient with diabetes with "cancer" for FDG PET/CT. Each center was called three times on three different days. The following data were collected: (1) blood glucose threshold for rescheduling an examination, (2) when or if to stop various medications, (3) fasting requirements, and (4) time-of-day scheduling preferences. Withheld information was not specifically requested. Descriptive statistics were calculated. RESULTS: There were 195 phone calls (mean duration, 2.9 min; range, 2-6 min). Relevant information was often withheld; withholding rates were as follows: blood glucose threshold, 71% (138 of 195); short-acting insulin instructions, 30% (59 of 195); long-acting insulin instructions, 99% (193 of 195); metformin instructions, 88% (179 of 195); fasting duration, 37% (72 of 195); and time-of-day scheduling preference, 91% (177 of 195). Mean provided data were as follows: blood glucose threshold, 195 mg/dL (range, 150-210 mg/dL); short-acting insulin withholding, 4.9 hours (range, 4-8 hours); long-acting insulin withholding, 12 hours (range, 12-24 hours); fasting duration, 5 hours (range, 4-8 hours); and preferred examination time, 91% (177 of 195). When specified (n = 18), morning scheduling was preferred (8% [15 of 195] versus 2% [3 of 195]). CONCLUSIONS: Diabetes-specific information is commonly withheld by nuclear medicine call centers throughout the United States when discussing oncologic FDG PET/CT despite local and national policies indicating its importance.

Metabolic response assessment with 18F-FDG PET/CT: inter-method comparison and prognostic significance for patients with non-small cell lung cancer.

OBJECTIVE: This study aimed to (1) compare the agreement of two evaluation methods of metabolic response in patients with non-small cell lung cancer (NSCLC) and determine their prognostic value and (2) explore an optimal cutoff of metabolic reduction to distinguish a more favorable subset of responders. METHODS: This is a secondary analysis of prospective studies. Enrolled patients underwent 18F-PET/CT within 2 weeks before, during, and months after radiotherapy (post-RT). Metabolic response was assessed using both Peter MacCallum (PM) method of qualitative visual assessment and University of Michigan (UM) method of semiquantitative measurement. The agreement between two methods determined response, and their prediction of outcome was analyzed. RESULTS: Forty-four patients with median follow-up of 25.2 months were analyzed. A moderate agreement was observed between PM- and UM-based response assessment (Kappa coefficient = 0.434), unveiling a significant difference in CMR rate (p = 0.001). Categorical responses derived from either method were significantly predictive of overall survival (OS) and progression-free survival (PFS) (p < 0.0001). Numerical percentage decrease of FDG uptake also showed significant correlations with survival, presenting a hazard ratio of 0.97 for both OS and PFS. A 75 % of SUV decrease was found to be the optimal cutoff to predict OS and 2-year progression. CONCLUSIONS: There was a modest discrepancy in metabolic response rates between PM and UM criteria, though both could offer predictive classification for survival. The percentage decrease provides an ordinal value that correlates with prolonged survival, recommending 75 % as the optimal threshold at identifying better responders.

Assessment of mild dementia with amyloid and dopamine terminal positron emission tomography.

We assessed the relationship between consensus clinical diagnostic classification and neurochemical positron emission tomography imaging of striatal vesicular monoamine transporters and cerebrocortical deposition of aß-amyloid in mild dementia. Seventy-five subjects with mild dementia (Mini-Mental State Examination score≥18) underwent a conventional clinical evaluation followed by 11C-dihydrotetrabenazine positron emission tomography imaging of striatal vesicular monoamine transporters and 11C-Pittsburgh compound-B positron emission tomography imaging of cerebrocortical aß-amyloid deposition. Clinical classifications were assigned by consensus of an experienced clinician panel. Neuroimaging classifications were assigned as Alzheimer's disease, frontotemporal dementia or dementia with Lewy bodies on the basis of the combined 11C-dihydrotetrabenazine and 11C-Pittsburgh compound-B results. Thirty-six subjects were classified clinically as having Alzheimer's disease, 25 as having frontotemporal dementia and 14 as having dementia with Lewy bodies. Forty-seven subjects were classified by positron emission tomography neuroimaging as having Alzheimer's disease, 15 as having dementia with Lewy bodies and 13 as having frontotemporal dementia. There was only moderate agreement between clinical consensus and neuroimaging classifications across all dementia subtypes, with discordant classifications in ∼35% of subjects (Cohen's κ=0.39). Discordant classifications were least frequent in clinical consensus Alzheimer's disease (17%), followed by dementia with Lewy bodies (29%) and were most common in frontotemporal dementia (64%). Accurate clinical classification of mild neurodegenerative dementia is challenging. Though additional post-mortem correlations are required, positron emission tomography imaging likely distinguishes subgroups corresponding to neurochemically defined pathologies. Use of these positron emission tomography imaging methods may augment clinical classifications and allow selection of more uniform subject groups in disease-modifying therapeutic trials and other prospective research involving subjects in the early stages of dementia.

Comparing fludeoxyglucose F18-PET assessment of regional cerebral glucose metabolism and [11C]dihydrotetrabenazine-PET in evaluation of early dementia and mild cognitive impairment.

OBJECTIVE: To compare assessment of regional cerebral metabolic changes with [(11)C]dihydrotetrabenazine (DTBZ)-positron emission tomography (PET) measurement of regional cerebral blood flow (K(1)) and fludeoxyglucose F18 (FDG)-PET measurement of regional cerebral glucose uptake (CMR(glc)) in a clinically representative sample of subjects with mild dementia and mild cognitive impairment (MCI). DESIGN: [(11)C]Dihydrotetrabenazine-PET K(1) and FDG-PET CMR(glc) measurements were performed. SETTING: University-based cognitive disorders clinic. PARTICIPANTS: Fifty subjects with either mild dementia (Mini-Mental State Examination score > or = 18) or MCI. Their results were compared with those of 80 normal control subjects. MAIN OUTCOME MEASURES: The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were compared with standard correlation analysis. The overall patterns of DTBZ-PET K(1) and FDG-PET CMR(glc) deficits were assessed with stereotaxic surface projections (SSPs) of parametric images. RESULTS: The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were highly correlated, both within and between subjects. The SSP maps of deficits in DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were markedly similar. The DTBZ-PET K(1) SSP maps exhibited a mild decrease in sensitivity relative to FDG-PET CMR(glc) maps. CONCLUSIONS: Both DTBZ-PET K(1) and FDG-PET CMR(glc) measurements provide comparable information in assessment of regional cerebral metabolic deficits in mild dementia and MCI. Blood flow measures can assess regional cerebral metabolism deficits accurately in mild dementia and MCI. Blood flow assessments of regional cerebral metabolic deficits can be combined with tracer binding results to improve utility of PET imaging in mild dementia and MCI.

Utility of delayed whole-body bone scintigraphy after directed three-phase scintigraphy.

OBJECTIVE: The purpose of this study was to determine the diagnostic yield and clinical importance of delayed whole-body bone scintigraphy in directed three-phase examinations. MATERIALS AND METHODS: The records of 400 consecutively registered patients who underwent combined three-phase and delayed whole-body (99m)Tc-methylene diphosphonate bone scintigraphy for a variety of indications were reviewed. Clinical indications, findings, recommendations, and outcome were assessed. RESULTS: Three-phase bone scintigraphy was performed on 156 men and boys and 244 women and girls (61%). Fifty-two patients (13%) were 17 years old or younger, and 236 patients (59%) were older than 40 years. The mean increase in study duration due to whole-body imaging was 25 minutes (range, 21-31 minutes). Excluding the three-phase area of interest, the whole-body examination had a normal tracer distribution in 131 examinations (33%), showed solely degenerative changes in 103 (26%), and showed findings unrelated to the area of interest in 166 patients (41%). In no case did the findings outside the area of interest alter the diagnosis or diagnostic certainty in the three-phase study, but those findings did generate 82 recommendations for additional diagnostic investigation. As a direct result of the recommendations, clinicians requested 18 radiographic, two CT, one MRI, and one ultrasound examinations, one additional bone scan, and two referrals to a consultant. Recommendations based on findings outside the three-phase area of interest affected treatment in one case: Temporomandibular joint uptake resulted in a referral for physical therapy. CONCLUSION: For most indications, delayed whole-body imaging after directed three-phase bone scintigraphy does not improve diagnostic yield, does not alter patient care, and may be an unnecessary use of medical resources.

Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome.

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision-making for both clinical care and future clinical trials.