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1.
Clin Nucl Med ; 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38914023

ABSTRACT: A 60-year-old man with a history of end-stage renal disease received renal transplant and had decreasing renal function 4 months later. Nuclear medicine renal flow and functional study showed severely decreased blood flow and decreased function of the right renal allograft. There was focal increased radiotracer uptake at blood flow phase around the anastomosis of the renal allograft artery and the right external iliac artery. CT angiogram revealed right external iliac artery pseudoaneurysm. Interventional radiology angiography reconfirmed the pseudoaneurysm and revealed stenosis at the proximal transplant renal artery. After stent placement, however, there was worse renal allograft blood flow.

2.
Int J Mol Sci ; 24(21)2023 Oct 30.
Article En | MEDLINE | ID: mdl-37958763

A modified version of the PGDx elioTM Plasma Resolve assay was validated as a laboratory-developed test (LDT) for clinical use in the Molecular Diagnostics Laboratory at Fox Chase Cancer Center. The test detects single nucleotide variants (SNVs) and small insertions and deletions (indels) in 33 target genes using fragmented genomic DNA extracted from plasma. The analytical performance of this assay was assessed with reference standard DNA and 29 samples from cancer patients and detected 66 SNVs and 23 indels. Using 50 ng of input DNA, the sensitivity was 95.5% to detect SNVs at 0.5% allele frequency, and the specificity was 92.3%. The sensitivity to detect indels at 1% allele frequency was 70.4%. A cutoff of 0.25% variant allele frequency (VAF) was set up for diagnostic reporting. An inter-laboratory study of concordance with an orthologous test resulted in a positive percent agreement (PPA) of 91.7%.


Circulating Tumor DNA , Neoplasms , Humans , Circulating Tumor DNA/genetics , Pathology, Molecular , Neoplasms/diagnosis , Neoplasms/genetics , INDEL Mutation , Molecular Diagnostic Techniques , High-Throughput Nucleotide Sequencing/methods , Mutation , Biomarkers, Tumor/genetics
3.
J Urol ; 210(3): 438-445, 2023 09.
Article En | MEDLINE | ID: mdl-37378576

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.


Adenoma, Oxyphilic , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Technetium Tc 99m Sestamibi , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Adenoma, Oxyphilic/diagnostic imaging , Single Photon Emission Computed Tomography Computed Tomography , Tomography, X-Ray Computed/methods , Tomography, Emission-Computed, Single-Photon/methods , Radiopharmaceuticals
4.
Horm Metab Res ; 54(12): 795-812, 2022 Dec.
Article En | MEDLINE | ID: mdl-35878617

Neuroendocrine tumors (NETs) occur in various regions of the body and present with complex clinical and biochemical phenotypes. The molecular underpinnings that give rise to such varied manifestations have not been completely deciphered. The management of neuroendocrine tumors (NETs) involves surgery, locoregional therapy, and/or systemic therapy. Several forms of systemic therapy, including platinum-based chemotherapy, temozolomide/capecitabine, tyrosine kinase inhibitors, mTOR inhibitors, and peptide receptor radionuclide therapy have been extensively studied and implemented in the treatment of NETs. However, the potential of immune checkpoint inhibitor (ICI) therapy as an option in the management of NETs has only recently garnered attention. Till date, it is not clear whether ICI therapy holds any distinctive advantage in terms of efficacy or safety when compared to other available systemic therapies for NETs. Identifying the characteristics of NETs that would make them (better) respond to ICIs has been challenging. This review provides a summary of the current evidence on the value of ICI therapy in the management of ICIs and discusses the potential areas for future research.


Neuroendocrine Tumors , Humans , Neuroendocrine Tumors/drug therapy , Immune Checkpoint Inhibitors/therapeutic use
5.
Clin Nucl Med ; 46(5): 439-441, 2021 May 01.
Article En | MEDLINE | ID: mdl-33661194

ABSTRACT: We present a case of increased FDG uptake in the lymph nodes after COVID-19 vaccine administration. Restaging PET/CT scan of a 70-year-old woman with a history of multiple relapsed Hodgkin lymphoma showed muscle activity in the left upper arm laterally, which is in the deep musculature of the left deltoid muscle. There was also increased activity in several normal-sized left axillary nodes as well. On further review of the patient's history, she had received her second shot of the Pfizer-BioNTech COVID-19 vaccine approximately 2 days before the restaging PET/CT scan.


COVID-19 Vaccines/adverse effects , Fluorodeoxyglucose F18/metabolism , Aged , Axilla , Female , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/immunology , Lymph Nodes/metabolism , Positron Emission Tomography Computed Tomography
6.
J Surg Res ; 243: 242-248, 2019 11.
Article En | MEDLINE | ID: mdl-31229791

BACKGROUND: A major challenge in identifying candidates for nonoperative management of locally advanced rectal cancer is predicting pathologic complete response (pCR) following chemoradiation. We evaluated pre- and post-CRT PET-CT imaging to predict pCR and prognosis in this set of patients undergoing resection after neoadjuvant therapy. METHODS: We retrospectively identified patients from 2002 to 2015 with locally advanced rectal cancer who underwent CRT, pre- and post-CRT PET-CT imaging, and resection. Univariate and multivariate analysis was performed and receiver operating characteristic (ROC) curves were generated to evaluate the association of PET-CT characteristics with pCR and survival. ROC curves were generated to define optimal cutoff points for predictive PET-CT characteristics. RESULTS: 125 patients were included. pCR rate was 28%, and follow-up was 48 mo. On multivariable analysis, patients who had a pCR had lower median post-CRT maximal standardized uptake value (SUVmax) (3.2 versus 5.2, P = 0.009) and higher median %SUV decrease (72 versus 58%, P = 0.009). ROC curves were generated for %SUVmax decrease (AUC = 0.70) and post-CRT SUV (AUC = 0.69). Post-CRT SUVmax <4.3 and %SUVmax decrease of >66% were equally predictive of pCR with a sensitivity of 65%, specificity of 72%, PPV of 44%, and NPV of 86%. Median 5-y overall and relapse-free survival were improved for patients with post-CRT SUV <4.3 (OS: 86 versus 66%, P = 0.01; RFS: 75 versus 52%, P = 0.01) or %SUV decrease of >66% (OS, 82 versus 66%, P = 0.05; RFS, 75 versus 54%, P = 0.01). CONCLUSIONS: PET/CT may be useful in identifying patients who did not achieve pCR, as well as overall survival in patients undergoing CRT for rectal cancer. Patients with a post-CRT SUV of >4.3 should be considered for operative management, as an estimated 86% of these patients will not have a pCR.


Adenocarcinoma/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Positron Emission Tomography Computed Tomography , Rectal Neoplasms/diagnostic imaging , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Philadelphia/epidemiology , Rectal Neoplasms/mortality , Rectal Neoplasms/therapy , Retrospective Studies
7.
J Clin Oncol ; 37(20): 1704-1712, 2019 07 10.
Article En | MEDLINE | ID: mdl-30768363

PURPOSE: The objective of this study was to determine the negative predictive value (NPV) of positron emission tomography (PET)/computed tomography (CT) for the clinically N0 neck on the basis of neck dissection. METHODS: Participants with newly diagnosed, first-time, head and neck squamous cell carcinoma (HNSCC) and at least one clinically N0 neck side for which dissection was planned were included. A total of 287 participants were prospectively enrolled from 23 American College of Radiology Imaging Network-qualified institutions. PET/CT was compared with findings at neck dissection. RESULTS: PET/CT scans and pathology findings were available for 270 N0 neck sides from 212 participants. For visual assessment, the NPV specific to the clinical-N0 sides was 0.868 (95% CI, 0.803 to 0.925). For dichotomized maximum standardized uptake value, the NPVs specific to the nodal basins were 0.940 (95% CI, 0.928 to 0.952) and 0.937 (95% CI, 0.925 to 0.949) at prespecified cutoffs of 2.5 and 3.5, respectively. The optimal cutoff maximum standardized uptake value was determined to be 1.8, with an NPV of 0.942 (95% CI, 0.930 to 0.953). The PET/CT-informed surgical treatment plan was changed in 51 of 237 participants (22%) compared with the PET/CT-blinded surgical plan. In 34 participants (14%), this led to planned dissection of additional nodal levels. In 12 participants (5%), this led to fewer planned dissected nodal levels. Negative PET/CT scans in N0 necks was true negative in 87% and false negative in 13%. CONCLUSION: [18F]fluorodeoxyglucose-PET/CT has high NPV for the N0 neck in T2 to T4 HNSCC. The surgical treatment plans on the basis of PET/CT findings may be changed in approximately 22% of this group. These findings suggest that [18F]fluorodeoxyglucose-PET/CT may assist the clinician in deciding on the best therapy for the clinically N0 neck in HNSCC. Well-designed clinical trials should be performed to test the outcome of omitting neck dissection by using PET/CT.


Carcinoma, Squamous Cell/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging , Neoplasm Staging/methods , Positron Emission Tomography Computed Tomography , Adult , Aged , Aged, 80 and over , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Neck/diagnostic imaging , Predictive Value of Tests , Prospective Studies , Radiology/standards , Treatment Outcome , Young Adult
8.
Clin Nucl Med ; 43(12): 909-917, 2018 Dec.
Article En | MEDLINE | ID: mdl-30325827

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.


Neoplasm Recurrence, Local/diagnostic imaging , Nuclear Medicine/standards , Positron Emission Tomography Computed Tomography/methods , Practice Guidelines as Topic , Prostatic Neoplasms/diagnostic imaging , Radiology/standards , Carboxylic Acids , Cyclobutanes , Fluorine Radioisotopes , Humans , Male , Positron Emission Tomography Computed Tomography/standards , Radiopharmaceuticals , Societies, Medical
9.
PET Clin ; 13(2): 249-268, 2018 Apr.
Article En | MEDLINE | ID: mdl-29482753

Combined PET/computed tomography is used for oncological indications. PET/computed tomography benefits from the metabolic information of PET and the anatomic localization of computed tomography. The integrated scanner provides data with accurate registration of anatomy and molecular information. Many physiologic conditions, normal variants, and benign lesions within the pelvis and the body can cause confusion and uncertainty. False-negative results owing to low 18F-fluorodeoxyglucose uptake from the tumor can produce diagnostic challenges and inaccurate conclusions. This article reviews normal variants and potential pitfalls encountered in PET assessment of gynecologic malignancies to provide useful information for the referring and reporting physicians.


Fluorodeoxyglucose F18 , Genital Neoplasms, Female/diagnostic imaging , Genital Neoplasms, Female/pathology , Positron Emission Tomography Computed Tomography/methods , Radiographic Image Enhancement , Adult , Aged , Artifacts , False Positive Reactions , Female , Genital Diseases, Female/diagnostic imaging , Genital Diseases, Female/pathology , Humans , Middle Aged , Positron Emission Tomography Computed Tomography/adverse effects , Positron-Emission Tomography/adverse effects , Positron-Emission Tomography/methods , Risk Assessment , Sensitivity and Specificity
10.
Clin Nucl Med ; 42(11): 890-892, 2017 Nov.
Article En | MEDLINE | ID: mdl-28806244

A 73-year-old man presented with fatigue and weight loss. He had CT-proven splenic mass with fistulous connection to the greater curvature of the stomach, which suggested abscess. FDG PET/CT confirmed gastrosplenic fistula in addition to active lymph nodes in the gastrohepatic ligament and epigastric region. Pathological examination after the biopsy of the spleen was consistent with diffuse large B-cell lymphoma. Chemotherapy was administered with close clinical follow-up and resulted in the resolution of fistula without requirement for surgery.


Fistula/diagnostic imaging , Fistula/etiology , Fluorodeoxyglucose F18 , Lymphoma/complications , Positron Emission Tomography Computed Tomography , Spleen , Stomach , Aged , Humans , Male
11.
J Nucl Med ; 58(1): 175-180, 2017 Jan.
Article En | MEDLINE | ID: mdl-27539844

Antibodies, and engineered antibody fragments, labeled with radioisotopes are being developed as radiotracers for the detection and phenotyping of diseases such as cancer. The development of antibody-based radiotracers requires extensive characterization of their in vitro and in vivo properties, including their ability to target tumors in an antigen-selective manner. In this study, we investigated the use of Cerenkov luminescence imaging (CLI) as compared with PET as a modality for evaluating the in vivo behavior of antibody-based radiotracers. METHODS: The anti-prostate-specific membrane antigen (PSMA) huJ591 antibody (IgG; 150 kDa) and its minibody (Mb; 80 kDa) format were functionalized with the chelator 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) and radiolabeled with the positron-emitting radionuclide 64Cu (half-life, 12.7 h). Immunoreactive preparations of the radiolabeled antibodies were injected into NCr nu/nu mice harboring PSMA-positive CWR22Rv1 and PSMA-negative PC-3 tumor xenografts. Tumor targeting was evaluated by both PET and CLI. RESULTS: 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb retained the ability to bind cell surface PSMA, and both radiotracers exhibited selective uptake into PSMA-positive tumors. Under the experimental conditions used, PSMA-selective uptake of 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb was observed by CLI as early as 3 h after injection, with tumor-to-background ratios peaking at 24 (IgG) and 16 (Mb) h after injection. Targeting data generated by CLI correlated with that generated by PET and necropsy. CONCLUSION: CLI provided a rapid and simple assessment of the targeting specificity and pharmacokinetics of the antibody-based PET radiotracers that correlated well with the behavior observed by standard PET imaging. Moreover, CLI provided clear discrimination between uptake kinetics of an intact IgG and its small-molecular-weight derivative Mb. These data support the use of CLI for the evaluation of radiotracer performance.


Antibodies, Monoclonal/pharmacokinetics , Luminescent Measurements/methods , Molecular Imaging/methods , Positron-Emission Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Radiopharmaceuticals/pharmacokinetics , Animals , Cell Line, Tumor , Drug Evaluation, Preclinical/methods , Humans , Male , Mice , Reproducibility of Results , Sensitivity and Specificity
12.
Hell J Nucl Med ; 18(2): 93-6, 2015.
Article En | MEDLINE | ID: mdl-26187206

OBJECTIVE: This retrospective study was carried out to determine the typical patterns of (18)F-FDG uptake in uncomplicated total hip arthroplasty (THA). SUBJECTS AND METHODS: (18)F-FDG-PET images of 62 asymptomatic THA patients who had undergone whole body scanning were evaluated for this retrospective study. The uptake was assessed qualitatively as positive or negative in the head/neck and the stem of the prosthesis. There were 76 hip prosthesis scans (34 left side and 42 right) and the average time following surgery was 75 months (range from 40 days to 372 months). Furthermore, the time course after surgery was subdivided into 3 time interval groups: Group I less than 2 years, Group II between 2 to 5 years, Group III more than 5 years. The regions of assessment were: head region including acetabulum and femoral head, femoral neck, trochanter, and femoral shaft. RESULTS: In patients who demonstrated increased peri-prosthetic (18)F-FDG uptake (59 of the 76 hip scans), the activity was confined to the femoral neck and proximal femoral shaft with the majority in the neck regions alone: 68% (40 of 59). Majority of the uptake was noted in the femoral neck, proximal shaft and trochanteric regions. CONCLUSION: Uptake of (18)F-FDG in the asymptomatic patients with THA is commonly visualized and appears to be confined to the proximal segment of the prosthesis with minimal or no activity in its femoral segment.


Arthroplasty, Replacement, Hip , Fluorodeoxyglucose F18/pharmacokinetics , Hip Joint/diagnostic imaging , Hip Joint/metabolism , Positron-Emission Tomography/methods , Adult , Aged , Aged, 80 and over , Female , Hip Joint/surgery , Humans , Male , Middle Aged , Postoperative Care , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Tissue Distribution , Treatment Outcome
13.
J Nucl Med ; 56(8): 1137-43, 2015 Aug.
Article En | MEDLINE | ID: mdl-25908829

UNLABELLED: PET/CT with the glucose analog (18)F-FDG has several potential applications for monitoring tumor response to therapy in patients with non-small cell lung cancer (NSCLC). A prerequisite for many of these applications is detailed knowledge of the repeatability of quantitative parameters derived from (18)F-FDG PET/CT studies. METHODS: The repeatability of the (18)F-FDG signal was evaluated in 2 prospective multicenter trials. Patients with advanced NSCLC (tumor stage III-IV) underwent two (18)F-FDG PET/CT studies while not receiving therapy. Tumor (18)F-FDG uptake was quantified by measurement of the maximum standardized uptake value within a lesion (SUVmax) and the average SUV within a small volume of interest around the site of maximum uptake (SUVpeak). Analysis was performed for the lesion in the chest with the highest (18)F-FDG uptake and a size of at least 2 cm (target lesion) as well as for up to 6 additional lesions per patient. Repeatability was assessed by Bland-Altman plots and calculation of 95% repeatability coefficients (RCs) of the log-transformed SUV differences. RESULTS: Test-retest repeatability was assessed in 74 patients (34 from the ACRIN 6678 trial and 40 from the Merck MK-0646-008 trial). SUVpeak was 11.57 ± 7.89 g/mL for the ACRIN trial and 6.89 ± 3.02 for the Merck trial. The lower and upper RCs were -28% (95% confidence interval [CI], -35% to -23%) and +39% (95% CI, 31% to 54%) in the ACRIN trial, indicating that a decrease of SUVpeak by more than 28% or an increase by more than 39% has a probability of less than 2.5%. The corresponding RCs from the Merck trial were -35% (95% CI, -42% to -29%) and +53% (95% CI, 41% to 72%). Repeatability was similar for SUVmax of the target lesion, averaged SUVmax, and averaged SUVpeak of up to 6 lesions per patient. CONCLUSION: The variability of repeated measurements of tumor (18)F-FDG uptake in patients with NSCLC is somewhat larger than previously reported in smaller single-center studies but comparable to that of gastrointestinal malignancies in a previous multicenter trial. The variability of measurements supports the definitions of tumor response according to PET Response Criteria in Solid Tumors.


Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Fluorodeoxyglucose F18 , Lung Neoplasms/diagnostic imaging , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Aged , Humans , Image Processing, Computer-Assisted , Middle Aged , Multimodal Imaging/methods , Prospective Studies , Radiopharmaceuticals , Reproducibility of Results , Treatment Outcome
14.
Clin Nucl Med ; 40(6): 523-5, 2015 Jun.
Article En | MEDLINE | ID: mdl-25608170

A 68-year-old man with a history of malignant melanoma in the right axilla underwent FDG PET/CT. The images demonstrated a focally increased activity in the subcutaneous tissue anterior to the distal left tibia, suggestive of metastasis. However, a gouty tophus was diagnosed pathologically after biopsy.


Fluorodeoxyglucose F18 , Melanoma/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Subcutaneous Tissue/pathology , Tomography, X-Ray Computed , Aged , Humans , Male , Medical Errors , Melanoma/pathology , Multimodal Imaging , Neoplasm Metastasis
15.
Mol Imaging Biol ; 16(5): 739-46, 2014 Oct.
Article En | MEDLINE | ID: mdl-24696183

PURPOSE: [(18) F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [(18) F]VM4-037 using whole-body PET/CT scans in healthy human volunteers. PROCEDURES: Successive whole-body PET/CT scans were performed after intravenous injection of [(18) F]VM4-037 in four healthy humans. The radiotracer uptakes in different organs were determined from the analysis of the PET scans. Human radiation doses were estimated using OLINDA/EXM software. RESULTS: High uptake of [(18) F]VM4-037 was observed in the liver and kidneys, with little clearance of activity during the study period, with mean standardized uptake values of ~35 in liver and ~22 in kidneys at ~1 h after injection. The estimated effective dose was 28 ± 1 µSv/MBq and the absorbed doses for the kidneys and liver were 273 ± 31 and 240 ± 68 µGy/MBq, respectively, for the adult male phantom. Hence, the effective dose would be 10 ± 0.5 mSv for the anticipated injected activity of 370 MBq, and the kidney and liver doses would be 101 ± 11 and 89 ± 25 mGy, respectively. CONCLUSIONS: [(18) F]VM4-037 displayed very high uptake in the liver and kidneys with little clearance of activity during the study period, resulting in these organs receiving the highest radiation doses among all bodily organs. Though the effective dose and the organ doses are within the limits considered as safe, the enhanced uptake of [(18) F]VM4-037 in the kidneys and liver will make the compound unsuitable for imaging overexpression of CA-IX in those two organs. However, the tracer may be suitable for imaging overexpression of CA-IX in lesions in other regions of the body such as in the lungs or head and neck region.


Antigens, Neoplasm/metabolism , Carbonic Anhydrases/metabolism , Dipeptides/pharmacokinetics , Healthy Volunteers , Positron-Emission Tomography , Radiometry , Sulfonamides/pharmacokinetics , Adult , Aged , Carbonic Anhydrase IX , Dipeptides/chemical synthesis , Dipeptides/chemistry , Female , Humans , Male , Middle Aged , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Tissue Distribution , Tomography, X-Ray Computed
17.
J Nucl Med ; 54(12): 2087-92, 2013 Dec.
Article En | MEDLINE | ID: mdl-24136934

UNLABELLED: (18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30-((2S,3R,4R,5R,6S)-6-((2-(4-(3-F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)-24-isopropyl-18-methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioic acid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from (18)F-CP-18. METHODS: Successive whole-body PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of (18)F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of (18)F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer. RESULTS: (18)F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high (18)F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 ± 4 µSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 ± 61 µGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 ± 2 µSv/MBq and 142 ± 15 µGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 ± 2.2 mSv for the 4.8-h interval, reduced to 8.3 ± 1.1 mSv for the 1-h interval. CONCLUSION: (18)F-CP-18 cleared rapidly through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both the effective dose and the bladder dose can be reduced by frequent voiding. From the radiation dosimetry perspective, the apoptosis imaging agent (18)F-CP-18 is suitable for human use.


Apoptosis , Glycopeptides/pharmacokinetics , Healthy Volunteers , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Triazoles/pharmacokinetics , Adult , Female , Humans , Male , Middle Aged , Radiometry , Tissue Distribution
18.
J Nucl Med Technol ; 41(1): 43-5, 2013 Mar.
Article En | MEDLINE | ID: mdl-23381679

A patient with metastatic papillary thyroid carcinoma (after surgical resection of tumor and positive lymph nodes) undergoing thyroid ablation therapy with (131)I is described. Whole-body scintigraphy was performed 1 wk after ablation therapy to evaluate the presence of residual disease. The whole-body images demonstrated an artifact caused by tracer accumulation in the patient's scalp related to recent hair coloring. Common etiologies of false-positive (131)I scintigraphic findings are briefly reviewed. The importance of taking preventative measures to decrease the number of false-positive findings and recognizing these findings when they occur is discussed.


Coloring Agents , Hair/chemistry , Scalp/diagnostic imaging , Adult , Carcinoma/diagnostic imaging , Carcinoma, Papillary , False Positive Reactions , Female , Humans , Iodine Radioisotopes , Radionuclide Imaging , Thyroid Cancer, Papillary , Thyroid Neoplasms/diagnostic imaging , Whole Body Imaging
19.
Thyroid ; 23(9): 1099-105, 2013 Sep.
Article En | MEDLINE | ID: mdl-23421588

BACKGROUND: The impact of extranodal extension (ENE) of metastatic papillary thyroid carcinoma (PTC) on short- and long-term clinical outcomes, including biochemical testing, has not been reported. METHODS: This single-institution National Cancer Institute-designated Comprehensive Cancer Center cohort study included patients with macroscopic metastases and excluded patients with gross residual disease after surgery, distant disease, or poorly differentiated papillary carcinoma. A suppressed or stimulated thyroglobulin (Tg) < 1 ng/mL, without suspicious imaging or anti-thyroglobulin antibodies, after radioactive iodine (RAI) treatment was termed an excellent or "complete biochemical response" (CR). RESULTS: Of 89 subjects included, 60 previously untreated patients underwent total thyroidectomy and therapeutic neck dissection; 29 additional patients underwent a neck dissection for persistence or recurrence after prior surgery and RAI administration. ENE, identified in 29 patients (33%), was associated with T4 classification (p = 0.02) and involvement of a greater number of nodes (median 11 vs. 5, p = 0.03). ENE was associated with a 20% increased risk of nodal persistence necessitating additional surgery (p = 0.02). In a multivariable analysis, ENE, T4 classification, and recurrence/persistence proved to be independent predictors of systemic disease progression (ENE: hazard ratio [HR] 4.3 [95% confidence interval (CI) 1.2-15], p = 0.02; T4 classification: HR 4.2 [CI 1.3-14], p = 0.01; recurrent/persistent status: HR 3.6 [CI 1.1-12], p = 0.035). Nodal or systemic disease progression was rare after a biochemical CR; in contrast, in previously untreated patients, stimulated Tg levels (sTg) > 50 ng/mL prior to initial RAI administration, heralded the progression of nodal disease, and also predicted the eventual development of systemic disease (p = 0.0001). Of those with a sTg > 50 ng/mL, over 70% underwent surgery for nodal persistence within five years. The presence of ENE diminished the odds of a biochemical CR (odds ratio 3.5% [CI 1.3-10], p = 0.02), and increased the probability that the sTg levels after surgery will exceed 50 ng/mL (odds ratio 5 [CI 1.2-21], p = 0.03). Following surgery for tumor persistence, 25% of those with ENE were rendered biochemically free of disease. CONCLUSIONS: ENE diminishes the probability of a biochemical CR after treatment for regional metastatic PTC, and increases the probability of tumor persistence after initial resection, likely from abundant metastasis. ENE and nodal persistence independently predict eventual systemic disease progression.


Carcinoma/secondary , Lymph Nodes/pathology , Thyroid Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Biomarkers/blood , Carcinoma/blood , Carcinoma/therapy , Carcinoma, Papillary , Disease Progression , Female , Humans , Kaplan-Meier Estimate , Logistic Models , Lymph Nodes/radiation effects , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neck Dissection , Neoplasm Recurrence, Local , Neoplasm Staging , Odds Ratio , Philadelphia , Proportional Hazards Models , Radiotherapy, Adjuvant , Reoperation , Retrospective Studies , Risk Factors , Thyroglobulin/blood , Thyroglobulin/immunology , Thyroid Cancer, Papillary , Thyroid Neoplasms/blood , Thyroid Neoplasms/therapy , Thyroidectomy , Time Factors , Treatment Outcome , Young Adult
20.
Biologics ; 6: 395-407, 2012.
Article En | MEDLINE | ID: mdl-23204838

Renal cell carcinoma (RCC) is a biologically heterogeneous disease, with many small renal masses (SRMs) exhibiting an indolent natural history, while others progress more rapidly to become life-threatening. Existing multiphase contrast-enhanced imaging methods, such as computed tomography or magnetic resonance imaging, cannot definitively distinguish between benign and malignant solid tumors or identify histologic subtype, and early results of molecular imaging studies (positron emission tomography [PET]) in the evaluation of SRMs have not improved on these established modalities. Alternative molecular markers/agents recognizing aberrant cellular pathways of cellular oxidative metabolism, DNA synthesis, and tumor hypoxia tracers are currently under development and investigation for RCC assessment, but to date none are yet clinically applicable or available. In contrast, immuno-PET offers highly selective binding to cancer-specific antigens, and might identify radiographically recognizable and distinct molecular targets. A phase I proof-of-concept study first demonstrated the ability of immuno-PET to discriminate between clear-cell RCC (ccRCC) and non-ccRCC, utilizing a chimeric monoclonal antibody to carbonic anhydrase IX (cG250, girentuximab) labeled with (124)I ((124)I-girentuximab PET); the study examined patients with renal masses who subsequently underwent standard surgical resection. A follow-up phase III multicenter trial confirmed that (124)I-cG250-PET can accurately and noninvasively identify ccRCC with high sensitivity (86%), specificity (87%), and positive predictive value (95%). In the challenge to appropriately match treatment of an incidentally identified SRM to its biological potential, this highly accurate and histologically specific molecular imaging modality demonstrates the ability of imaging to provide clinically important preoperative diagnostic information, which can result in optimal and personalized therapy.

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