Publications by authors named "Thomas A Hope"

143 Publications

Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer.

Eur Urol 2021 Apr 8. Epub 2021 Apr 8.

Department of Urology, University of California-San Francisco, San Francisco, CA, USA; Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA. Electronic address:

F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1-4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. PATIENT SUMMARY: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.
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http://dx.doi.org/10.1016/j.eururo.2021.03.017DOI Listing
April 2021

Prostate-specific Membrane Antigen PET in Prostate Cancer.

Radiology 2021 Mar 30:202771. Epub 2021 Mar 30.

From the Department of Radiology and Biomedical Imaging (C.L.H., S.C.B., T.A.H.) and Helen Diller Family Comprehensive Cancer Center (S.C.B., T.A.H.), University of California San Francisco, 505 Parnassus Ave, M391, San Francisco, CA 94143; Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Md (A.S., S.P.R.); Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, Calif (J.C.); Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany (W.P.F.); Department of Nuclear Medicine, Technical University of Munich, Munich, Germany (M.E.); Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital, Sydney, Australia (L.E.); Prostate Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia (M.S.H.); and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia (M.S.H.).

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.
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http://dx.doi.org/10.1148/radiol.2021202771DOI Listing
March 2021

MR-based Attenuation Correction for Brain PET Using 3D Cycle-Consistent Adversarial Network.

IEEE Trans Radiat Plasma Med Sci 2021 Mar 3;5(2):185-192. Epub 2020 Jul 3.

Center for Advanced Medical Computing and Analysis, Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.

Attenuation correction (AC) is important for the quantitative merits of positron emission tomography (PET). However, attenuation coefficients cannot be derived from magnetic resonance (MR) images directly for PET/MR systems. In this work, we aimed to derive continuous AC maps from Dixon MR images without the requirement of MR and computed tomography (CT) image registration. To achieve this, a 3D generative adversarial network with both discriminative and cycle-consistency loss (Cycle-GAN) was developed. The modified 3D U-net was employed as the structure of the generative networks to generate the pseudo CT/MR images. The 3D patch-based discriminative networks were used to distinguish the generated pseudo CT/MR images from the true CT/MR images. To evaluate its performance, datasets from 32 patients were used in the experiment. The Dixon segmentation and atlas methods provided by the vendor and the convolutional neural network (CNN) method which utilized registered MR and CT images were employed as the reference methods. Dice coefficients of the pseudo-CT image and the regional quantification in the reconstructed PET images were compared. Results show that the Cycle-GAN framework can generate better AC compared to the Dixon segmentation and atlas methods, and shows comparable performance compared to the CNN method.
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http://dx.doi.org/10.1109/trpms.2020.3006844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993643PMC
March 2021

High-Specific-Activity-I-MIBG versus Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.

Clin Cancer Res 2021 Mar 8. Epub 2021 Mar 8.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland.

Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-I-MIBG therapy was approved by the FDA and both Lu-DOTATATE and I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3703DOI Listing
March 2021

Accuracy of F-fluorocholine PET for the detection of parathyroid adenomas: prospective single center study.

J Nucl Med 2021 Mar 5. Epub 2021 Mar 5.

University of California, San Francisco, United States.

The purpose of this prospective study was to determine the correct localization rate (CLR) of F-fluorocholine (FCH) positron emission tomography (PET) for the detection of parathyroid adenomas in comparison to sestamibi imaging. This was a single-arm prospective trial. Ninety-eight patients with biochemical evidence of primary hyperparathyroidism were imaged prior to parathyroidectomy using FCH PET/MRI. Sestamibi imaging performed separately from the study was evaluated for comparison. The primary endpoint of the study was the CLR on a patient level. Each imaging study was interpreted by 3 blinded readers on a per-region basis. Lesions were validated by histopathologic analysis of surgical specimens. Of the 98 patients who underwent FCH imaging, 77 subsequently underwent parathyroidectomy and 60 of those had sestamibi imaging. The CLR for FCH in patients who underwent parathyroidectomy based on the blinded reader consensus was 75% [0.63, 0.82]. In patients who underwent surgery and had an available sestamibi study, the CLR increased from 17% [0.10, 0.27] for sestamibi to 70% [0.59, 0.79] for FCH PET. In this prospective study using blinded readers, the CLR for FCH was 75%. In patients with paired sestamibi, the use of FCH PET increased the CLR from 17% to 70%. FCH PET is a superior imaging modality for the localization of parathyroid adenomas.
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http://dx.doi.org/10.2967/jnumed.120.256735DOI Listing
March 2021

E-PSMA: the EANM standardized reporting guidelines v1.0 for PSMA-PET.

Eur J Nucl Med Mol Imaging 2021 Feb 19. Epub 2021 Feb 19.

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany.

Rationale: The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.

Methods: A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.

Results: According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.

Conclusions: The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.
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http://dx.doi.org/10.1007/s00259-021-05245-yDOI Listing
February 2021

More Answers and More Questions About Radiotherapy for Metastatic Prostate Cancer.

JAMA Oncol 2021 Apr;7(4):563-564

Department of Radiology and Biomedical Imaging, University of California, San Francisco.

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http://dx.doi.org/10.1001/jamaoncol.2020.7708DOI Listing
April 2021

PSMA-targeted radiopharmaceutical therapy in patients with metastatic castration-resistant prostate cancer.

Lancet 2021 Feb 11;397(10276):768-769. Epub 2021 Feb 11.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine and Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA.

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http://dx.doi.org/10.1016/S0140-6736(21)00349-4DOI Listing
February 2021

The Role of PSMA PET/CT and PET/MRI in the Initial Staging of Prostate Cancer.

Eur Urol Focus 2021 Mar 2;7(2):258-266. Epub 2021 Feb 2.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA; Department of Radiology, San Francisco VA Medical Center, San Francisco, CA, USA.

Context: Prostate cancer (PCa) is the most common solid organ malignancy in men and is the third leading cause of cancer death. Accurate methods for the detection and staging of PCa are necessary to determine the extent of disease and inform treatment options.

Objective: To review the performance and diagnostic accuracy of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in the initial staging of PCa and evaluate its impact on definitive therapy planning.

Evidence Acquisition: A comprehensive literature search was performed using PubMed. References from retrieved articles and recommendations from the authors were also included.

Evidence Synthesis: PSMA PET has moderately high sensitivity and specificity for detecting intraprostatic tumors and moderately high sensitivity for detecting regional and extrapelvic metastases, compared with conventional imaging. PSMA PET can also have an important role in the presurgical detection of extraprostatic disease and can guide surgical planning. Additionally, PSMA PET has proven to be an effective tool for planning definitive radiation therapy in treatment-naïve patients.

Conclusions: PSMA PET has a promising role in the initial staging of PCa and informing appropriate treatment options. Further research is necessary to evaluate the appropriate role of PSMA PET in management changes, and to understand the appropriate management of patients with metastatic disease.

Patient Summary: We reviewed the diagnostic accuracy and treatment impact of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in the initial staging of prostate cancer (PCa). We conclude that PSMA PET is effective at imaging initial PCa and may result in the modification of treatment plans for patients.
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http://dx.doi.org/10.1016/j.euf.2021.01.016DOI Listing
March 2021

Oliver Sartor Talks with Thomas A. Hope, Jeremie Calais, and Wolfgang P. Fendler About FDA Approval of PSMA.

J Nucl Med 2021 02;62(2):146-148

Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

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http://dx.doi.org/10.2967/jnumed.120.261834DOI Listing
February 2021

Assessment and comparison of fluorocholine PET and sestamibi scans in identifying parathyroid adenomas: a meta-analysis.

J Nucl Med 2021 Jan 15. Epub 2021 Jan 15.

University of California, San Francisco, United States.

Hyperparathyroidism is an endocrine disorder caused by one or more hyperfunctioning parathyroid glands. Current imaging consisting of ultrasound and Tc-Sestamibi (sestamibi) is imprecise, making localization difficult. F-Fluorocholine (FCH) Positron Emission Tomorography (PET) has recently shown promise in pre-surgical localization of parathyroid adenomas. The primary aim of this study is to summarize the sensitivities and specificities of studies using FCH PET to localize hyperparathyroidism. A secondary aim is to summarize a subset of studies in which sestamibi scans were also used, and to compare the performance of the two modalities. We searched MEDLINE and EMBASE databases following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Twenty studies were included for quantitative assessment in our meta-analysis. A random effect model and a hierarchical summary receiver operating characteristic model was used to summarize the sensitivity of FCH PET in detecting abnormal parathyroid adenomas. We used the same methodology to assess sensitivity of sestamibi, as a comparison to FCH PET. FCH PET had a high sensitivity for the detection of abnormal parathyroid adenomas 0.97 (0.96-0.98). In the subpopulation where both FCH and sestamibi were reported, FCH also had a higher sensitivity of 0.96 (0.94-0.98), compared with 0.54 (0.29-0.79) for sestamibi (p<0.001). FCH PET demonstrates high localization accuracy in patients with hyperparathyroidism. This meta-analysis supports the use of FCH in patients with hyperparathyroidism over sestamibi.
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http://dx.doi.org/10.2967/jnumed.120.257303DOI Listing
January 2021

Update from PSMA-SRT Trial NCT03582774: A Randomized Phase 3 Imaging Trial of Prostate-specific Membrane Antigen Positron Emission Tomography for Salvage Radiation Therapy for Prostate Cancer Recurrence Powered for Clinical Outcome.

Eur Urol Focus 2021 Mar 30;7(2):238-240. Epub 2020 Dec 30.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

The purpose of this randomized trial is to evaluate the success rate of salvage radiation therapy for recurrence of prostate cancer after radical prostatectomy, with and without planning based on prostate-specific membrane antigen positron emission tomography/computed tomography. Enrollment has been completed and patients are being followed for 5yr.
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http://dx.doi.org/10.1016/j.euf.2020.12.009DOI Listing
March 2021

Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.

Phys Med Biol 2021 Jan 29;66(3):035016. Epub 2021 Jan 29.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco CA, United States of America.

Acute hematologic toxicity is a frequent adverse effect of beta-emitter targeted radionuclide therapies (TRTs). Alpha emitters have the potential of delivering high linear energy transfer (LET) radiation to the tumor attributed to its shorter range. Antibody-based TRTs have increased blood-pool half-lives, and therefore increased marrow toxicity, which is a particular concern with alpha emitters. Accurate 3D absorbed dose calculations focusing on the interface region of blood vessels and bone can elucidate energy deposition patterns. Firstly, a cylindrical geometry model with a central blood vessel embedded in the trabecular tissue was modeled. Monte Carlo simulations in GATE were performed considering beta (Lu, Y) and alpha emitters (At, Ac) as sources restricted to the blood pool. Subsequently, the radioactive sources were added in the trabecular bone compartment in order to model bone marrow metastases infiltration (BMMI). Radial profiles, dose-volume histograms and voxel relative differences were used to evaluate the absorbed dose results. We demonstrated that alpha emitters have a higher localized energy deposition compared to beta emitters. In the cylindrical geometry model, when the sources are confined to the blood pool, the dose to the trabecular bone is greater for beta emitting radionuclides, as alpha emitters deposit the majority of their energy within 70 μm of the vessel wall. In the BMMI model, alpha emitters have a lower dose to untargeted trabecular bone. Our results suggest that when alpha emitters are restricted to the blood pool, as when labeled to antibodies, hematologic toxicities may be lower than expected due to differences in the microdistribution of delivered absorbed dose.
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http://dx.doi.org/10.1088/1361-6560/abd3efDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880907PMC
January 2021

From Compassionate Use to Phase 3 Trial: The Impact of Germany's PSMA-617 Literature.

Authors:
Thomas A Hope

J Nucl Med 2020 12;61(Suppl 2):255S-256S

Department of Radiology and Biomedical Imaging, University of California, San Francisco, and Department of Radiology, San Francisco VA Medical Center, San Francisco, California

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http://dx.doi.org/10.2967/jnumed.120.252122DOI Listing
December 2020

Updates to the Appropriate-Use Criteria for Somatostatin Receptor PET.

Authors:
Thomas A Hope

J Nucl Med 2020 12;61(12):1764

University of California, San Francisco, San Francisco, California

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http://dx.doi.org/10.2967/jnumed.120.257808DOI Listing
December 2020

Evaluating determinants of receipt of molecular imaging in biochemical recurrent prostate cancer.

Cancer Med 2021 Jan 28;10(1):62-69. Epub 2020 Nov 28.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.

Background: Molecular imaging with novel radiotracers is changing the treatment landscape in prostate cancer (PCa). Currently, standard of care includes either conventional and molecular imaging at time of biochemical recurrence (BCR). This study evaluated the determinants of and cost associated with utilization of molecular imaging for BCR PCa.

Methods: This is a retrospective observational cohort study among men with BCR PCa from June 2018 to May 2019. Multivariate logistic regression models were employed to analyze the primary outcome: receipt of molecular imaging (e.g. Fluciclovine PET and Prostate Specific Membrane Antigen PET) as part of diagnostic work-up for BCR PCa. Multivariate linear regression models were used to analyze the secondary outcome: overall healthcare cost within a 1-year time frame.

Results: The study sample included 234 patients; 79.1% White, 2.1% Black, 8.5% Asian/Pacific Islander, and 10.3% Other. The majority were 55 years or older (97.9%) and publicly insured (74.8%). Analysis indicated a one-unit reduction in PSA is associated with 1.3 times higher likelihood of receiving molecular imaging (p < 0.01). Analysis found that privately insured patients were associated with approximately $500,000 more in hospital reimbursement (p < 0.01) as compared to the publicly insured. Additionally, a one-unit increase in PSA is associated with $6254 increase in hospital reimbursement or an increase in total payments by 2.1% (p < 0.05).

Conclusions: Higher PSA was associated with lower likelihood for molecular imaging and higher cost in a one-year time frame. Higher cost was also associated with private insurance, but there was no clear relationship between insurance type and imaging type.
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http://dx.doi.org/10.1002/cam4.3555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826487PMC
January 2021

Gallium-68 prostate-specific membrane antigen ([Ga]Ga-PSMA-11) PET for imaging of thyroid cancer: a feasibility study.

EJNMMI Res 2020 Oct 22;10(1):128. Epub 2020 Oct 22.

Department of Radiology and Biomedical Imaging, University of California San Francisco, 185 Berry Street, Suite 350, Lobby 6, Box 0946, San Francisco, CA, 94143, USA.

Background: Prostate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.

Methods: Eligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[F]FDG PET and/or I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[F]FDG PET CT/MRI for lesion location and relative intensity.

Results: Twelve patients underwent [Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.

Conclusions: [Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.
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http://dx.doi.org/10.1186/s13550-020-00720-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581659PMC
October 2020

Introduction to the D-SPECT for Technologists: Workflow Using a Dedicated Digital Cardiac Camera.

J Nucl Med Technol 2020 Dec 5;48(4):297-303. Epub 2020 Oct 5.

Department of Radiology, San Francisco VA Medical Center, San Francisco, California

The D-SPECT is a dedicated cardiac camera that incorporates a solid-state semiconductor detector. This camera differs greatly from conventional SPECT/CT systems, resulting in significant differences in patient imaging. This continuing education article focuses on the specifications of both SPECT/CT and D-SPECT systems, radiopharmaceutical dosing requirements, imaging workflows, and some disadvantages of using each camera system. When used properly, the D-SPECT system can provide high-quality cardiac images with lower doses and faster exam times than conventional SPECT/CT systems.
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http://dx.doi.org/10.2967/jnmt.120.254870DOI Listing
December 2020

Disparities in PET imaging for prostate cancer at a tertiary academic medical center.

J Nucl Med 2020 Sep 25. Epub 2020 Sep 25.

University of California, San Francisco.

F-fluciclovine and Ga-prostate specific membrane antigen (PSMA) are novel PET imaging radiotracers used to characterize disease burden in biochemical recurrent prostate cancer. F-fluciclovine was FDA-approved in 2016 and is reimbursed through public and private payers, while Ga-PSMA-11 is considered investigational and accessed through clinical trials. The purpose of this study was to evaluate the demographic differences between patients receiving F-fluciclovine and Ga-PSMA-11 at a tertiary academic medical center. All F-fluciclovine and Ga-PSMA-11 PET studies performed at the University of California, San Francisco (UCSF) between October 2015 and January 2020 were reviewed. Age, race/ethnicity, primary language, body mass index, insurance type, and home address were obtained through the electronic medical record database. Home addresses were geocoded to Census Block Group and assigned to neighborhood socioeconomic status (nSES) using a previously described composite measure. A logistic regression model was used to evaluate the association between each of the predictor variables and the type of PET imaging received. This study included 1,756 patients; 1,502 patients received Ga-PSMA-11 and 254 patients received F-fluciclovine. Black patients had increased odds of receiving imaging with F-fluciclovine versus Ga-PSMA-11 compared to non-Hispanic white patients. (OR 3.88, 95% CI 1.90-7.91,). There were no statistically significant differences in other patient demographics between the two groups. In patients receiving molecular imaging for prostate cancer at a single U.S. tertiary medical center, access to Ga-PSMA-11 for Black patients was limited, compared to non-Hispanic white patients, by a factor of nearly four.
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http://dx.doi.org/10.2967/jnumed.120.251751DOI Listing
September 2020

A Conversation Between Joseph Osborne and Thomas Hope.

J Nucl Med 2020 09;61(9):1275-1277

University of California, San Francisco, San Francisco, California.

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http://dx.doi.org/10.2967/jnumed.120.255141DOI Listing
September 2020

NRG Oncology Updated International Consensus Atlas on Pelvic Lymph Node Volumes for Intact and Postoperative Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 Jan 27;109(1):174-185. Epub 2020 Aug 27.

Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin.

Purpose: In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.

Methods And Materials: A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.

Results: Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm, intact node positive case was 409 cm, and intact node negative case was 342 cm. Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached.

Conclusions: Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736505PMC
January 2021

Ga-PSMA-11 PET/MRI: determining ideal acquisition times to reduce noise and increase image quality.

EJNMMI Phys 2020 Aug 26;7(1):54. Epub 2020 Aug 26.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.

Background: In this study, we investigate the impact of increased PET acquisition time per bed position on lesion detectability, standard uptake value, and image noise in Ga-PSMA-11 PET/MRI scans.

Methods: Scans of twenty patients were analyzed in this study. Patients were injected with Ga-PSMA-11 (mean, 5.50 ± 1.49 mCi) and imaged on a 3.0 T time-of-flight PET/MRI. PET images were retrospectively reconstructed using 0.5, 1, 2, 4, 7, and 10 min of PET data. Lesion detectability was evaluated on a 5-point Likert Scale for each lesion in each reconstruction. Quantitative analysis was performed measuring image noise and lesion uptake.

Results: A total of 55 lesions were identified, and lesion detectability increased from 2.07 ± 1.14 for 0.5 min to 4.93 ± 0.26 for 10 min (p < 0.001), with no significant difference detected between 7 and 10 min of scan time. Average SUV decreased from 9.89 ± 6.62 for 0.5 min to 8.64 ± 6.81 for 10 min. Noise decreased from 0.72 ± 0.22 for 0.5 min to 0.31 ± 0.12 for 10 min (p < 0.001) and were nearly equivalent between 7 and 10 min. Pairwise interaction terms between size, SUV, and scan time were all found to be significant, although the interaction term between SUV and scan time was found to be the most significant.

Conclusions: Increased acquisition duration improves image quality by increasing detectability and reducing noise. In patients with biochemical recurrence, increased acquisition time up to 7 min improves lesion detection.
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http://dx.doi.org/10.1186/s40658-020-00322-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447708PMC
August 2020

False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial.

Eur J Nucl Med Mol Imaging 2021 Feb 17;48(2):501-508. Epub 2020 Aug 17.

Departments of Radiology and Biomedical Imaging and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.

Purpose: Readers need to be informed about potential pitfalls of [Ga]Ga-PSMA-11 PET interpretation.

Methods: Here we report [Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer.

Results: Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (n = 5), pelvic nodes (n = 1), and extra pelvic lesions (n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.

Conclusion: [Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.

Trial Registration Number: ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.
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http://dx.doi.org/10.1007/s00259-020-04945-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835157PMC
February 2021

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors.

Pancreas 2020 08;49(7):863-881

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

This article is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The guidelines panel consisted of medical oncologists, pathologists, gastroenterologists, endocrinologists, and radiologists. The panel reviewed a series of questions regarding the medical management of patients with pancreatic neuroendocrine tumors as well as questions regarding surveillance after resection. The available literature was reviewed for each of the question and panel members voted on controversial topics, and the recommendations were included in a document circulated to all panel members for a final approval.
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http://dx.doi.org/10.1097/MPA.0000000000001597DOI Listing
August 2020

Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society Guidelines for the Diagnosis and Management of Patients With Lung Neuroendocrine Tumors: An International Collaborative Endorsement and Update of the 2015 European Neuroendocrine Tumor Society Expert Consensus Guidelines.

J Thorac Oncol 2020 10 11;15(10):1577-1598. Epub 2020 Jul 11.

Department of Oncology, Monash Health, Monash University, Melbourne, Victoria, Australia.

Lung neuroendocrine tumors (LNETs) are uncommon cancers, and there is a paucity of randomized evidence to guide practice. As a result, current guidelines from different neuroendocrine tumor societies vary considerably. There is a need to update and harmonize global consensus guidelines. This article reports the best practice guidelines produced by a collaboration between the Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society. We performed a formal endorsement and updating process of the 2015 European Neuroendocrine Tumor Society expert consensus article on LNET. A systematic review from January 2013 to October 2017 was conducted to procure the most recent evidence. The stepwise endorsement process involved experts from all major subspecialties, patients, and advocates. Guided by discussion of the most recent evidence, each statement from the European Neuroendocrine Tumor Society was either endorsed, modified, or removed. New consensus statements were added if appropriate. The search yielded 1109 new publications, of which 230 met the inclusion criteria. A total of 12 statements were endorsed, 22 statements were modified or updated, one was removed, and two were added. Critical answered questions for each topic in LNET were identified. Through the consensus process, guidelines for the management of patients with local and metastatic neuroendocrine tumors have been updated to include both recent evidence and practice changes relating to technological and definitional advances. The guidelines provide clear, evidence-based statements aimed at harmonizing the global approach to patients with LNETs, on the basis of the principles of person-centered and LNET-specific care. The importance of LNET-directed research and person-centered care throughout the diagnosis, treatment, and follow-up journey is emphasized along with directions for future collaborative research.
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http://dx.doi.org/10.1016/j.jtho.2020.06.021DOI Listing
October 2020

PET/Magnetic Resonance Imaging Applications in Abdomen and Pelvis.

Magn Reson Imaging Clin N Am 2020 Aug;28(3):369-380

Joint Department Medical Imaging, University Health Network, 585 University Avenue, Toronto, Ontario M5G 2N2, Canada. Electronic address:

This article gives a brief overview of the current clinical applications in PET/magnetic resonance (MR) imaging in abdominal diseases. Initial technical developments concentrated on improvement of attenuation correction. Significant enhancements have been achieved, which is now considered solved and useable for clinical routine. For clinical applicability, a considerable amount of work was done by several groups to tailor disease-specific protocols for PET/MR imaging. Those protocols focused on providing complementary diagnostic information from the PET as well as from the MR imaging component. Successful protocol implementation has been performed in liver metastases, pancreatic cancer, gynecologic tumors, and especially prostate cancer.
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http://dx.doi.org/10.1016/j.mric.2020.03.010DOI Listing
August 2020

Peptide Receptor Radionuclide Therapy During the COVID-19 Pandemic: Are There Any Concerns?

J Nucl Med 2020 Aug 23;61(8):1094-1095. Epub 2020 Jun 23.

Department of Nuclear Medicine, University Hospital Essen, Essen, Germany, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California.

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http://dx.doi.org/10.2967/jnumed.120.249136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413236PMC
August 2020

Intraarterial Peptide Receptor Radionuclide Therapy Using Y-DOTATOC for Hepatic Metastases of Neuroendocrine Tumors.

J Nucl Med 2021 02 8;62(2):221-227. Epub 2020 Jun 8.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California.

Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from intravenous administration as previously reported in the literature. PRRT-naïve adult neuroendocrine tumor patients with liver-dominant metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous Ga-DOTATOC. Then, 3.5 ± 0.2 GBq (94.7 ± 5.4 mCi) of Y-DOTATOC were administered into the proper hepatic artery over 30 min. The first 5 patients also received intraarterial Ga-DOTATOC and underwent PET/CT. All patients were followed for response (RECIST, version 1.1) (primary aim 2, safety) and toxicity (Common Terminology Criteria for Adverse Events, version 4.0) (primary aim 1, efficacy) for at least 6 mo, with optional follow-up for up to 1 y. In the subset of 5 patients who underwent both intravenous and intraarterial Ga-DOTATOC PET/CT, tumor SUV was compared between intravenous and intraarterial administration for hepatic tumors, intrahepatic tumors, and uninvolved background organs (secondary aim, intravenous vs. intraarterial uptake). The study was terminated after a planned analysis of the first 10 patients because of lack of efficacy. The best response was stable disease in 90% (9/10 patients) and progressive disease in 10% (1/10 patients) at 3 mo, and stable disease in 8 of 10 patients and progressive disease in 2 of 10 patients at 6 mo. One additional patient developed progressive disease after the 6-mo follow-up period but within the optional 1-y follow-up period. No partial response or complete response was observed. The 2 patients with the highest liver tumor burden died within 6 mo of treatment, with treatment considered a possible contributor. Patients who received intraarterial administration failed to demonstrate higher uptake by hepatic metastases than patients who received intravenous administration, with a median intraarterial-to-intravenous SUV ratio of 0.81 (range, 0.36-2.09) on a lesion level. Our study found that administration of PRRT via the proper hepatic artery did not reproduce the increase in hepatic tumor uptake that was previously reported. In addition, the single treatment using Y-DOTATOC did not induce tumor shrinkage, indicating that more treatment cycles may be required. Possible safety concerns in patients with a high liver tumor burden should inform patient selection for future studies.
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http://dx.doi.org/10.2967/jnumed.119.241273DOI Listing
February 2021

Impact of Ga-PSMA-11 PET on the Management of Recurrent Prostate Cancer in a Prospective Single-Arm Clinical Trial.

J Nucl Med 2020 12 1;61(12):1793-1799. Epub 2020 May 1.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California

Prostate-specific membrane antigen (PSMA) ligand PET induces management changes in patients with prostate cancer. We aim to better characterize the impact of Ga-PSMA-11 PET (Ga-PSMA PET) on management of recurrent prostate cancer in a large prospective cohort. We report management changes after Ga-PSMA PET, a secondary endpoint of a prospective multicenter trial in men with biochemical recurrence of prostate cancer. Pre-PET (Q1), post-PET (Q2), and posttreatment (Q3) questionnaires were sent to referring physicians recording site of recurrence and intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Q1 and Q2 response was collected for 382 of 635 patients (60%, intended cohort), and Q1, Q2, and Q3 response was collected for 206 patients (32%, implemented cohort). An intended management change occurred in 260 of 382 (68%) patients. The intended change was considered major in 176 of 382 (46%) patients. Major changes occurred most often for patients with prostate-specific antigen of 0.5 to less than 2.0 ng/mL (81/147, 55%). By analysis of stage groups, management change was consistent with PET disease location, that is, a majority of major changes toward active surveillance (47%) for unknown disease site (103/382, 27%), toward local or focal therapy (56%) for locoregional disease (126/382, 33%), and toward systemic therapy (69% M1a; 43% M1b/c) for metastatic disease (153/382, 40%). According to Q3 responses, the intended management was implemented in 160 of 206 (78%) patients. In total, 150 intended diagnostic tests, mostly CT ( = 43, 29%) and bone scans or F-NaF PET ( = 52, 35%), were prevented by Ga-PSMA PET; 73 tests, mostly biopsies ( = 44, 60%) as requested by the study protocol, were triggered. According to referring physicians, sites of recurrence were clarified by Ga-PSMA PET, and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer.
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http://dx.doi.org/10.2967/jnumed.120.242180DOI Listing
December 2020

Factors Predicting Metastatic Disease in Ga-PSMA-11 PET-Positive Osseous Lesions in Prostate Cancer.

J Nucl Med 2020 12 17;61(12):1779-1785. Epub 2020 Apr 17.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics. Fifty-six prostate cancer patients (18 before prostatectomy and 38 with biochemical recurrence) who underwent Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, we measured biologic volume; size; PSMA Reporting and Data System (RADS) rating; SUV; and ratio of lesion SUV to liver, blood pool, and background bone SUV Differences between benign and malignant lesions were evaluated for statistical significance, and cutoffs for these parameters were determined to maximize diagnostic accuracy. Among 56 participants, 13 (22.8%) had false-positive osseous Ga-PSMA-11 findings and 43 (76.8%) had true-positive osseous Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cutoffs resulting in statistically significant ( < 0.005) differences between benign and malignant lesions were a PSMA RADS rating of at least 4, an SUV of at least 4.1, and SUV ratios of at least 2.11 for lesion to blood pool, at least 0.55 for lesion to liver, and at least 4.4 for lesion to bone. These measurements corresponded to a lesion-based Ga-PSMA-11 PET lesion detection rate of 80%, 93%, 89%, 21%, and 89%, respectively, for malignancy, and a specificity of 73%, 73%, 73%, 93%, and 60%, respectively. PSMA RADS rating, SUV, and SUV ratio for lesion to blood pool can help differentiate benign from malignant lesions on Ga-PSMA-11 PET. An SUV ratio of more than 2.2 for lesion to blood pool is a reasonable parameter to support image interpretation and presented a superior lesion detection rate and specificity when compared with visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on Ga-PSMA-11 PET/MRI and PET/CT.
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http://dx.doi.org/10.2967/jnumed.119.241174DOI Listing
December 2020