Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

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.

Validation of a Molecular Diagnostic Test for Circulating Tumor DNA by Next-Gen Sequencing.

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%.

Immune Checkpoint Inhibitor Therapy in Neuroendocrine Tumors.

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.

Impact of PET/CT for Restaging Patients With Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiation.

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.

Patterns of 18F-FDG PET images in patients with uncomplicated total hip arthroplasty.

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.

Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUV(max) and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.

Renal Transplant Anastomotic Pseudoaneurysm and Stenosis at the Proximal Transplant Renal Artery and Worse Renal Blood Flow After Stent Placement.

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.

Predicting pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using 18FDG-PET/CT.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15-30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC. METHODS: This is a retrospective review of patients with EUS-staged T3-T4, N+rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002-2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan-Meier estimation evaluated significant predictors of survival. RESULTS: Seventy patients (age 62 years; 42M:28F) with preoperative stage T3 (n=61) and T4 (n=9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P=0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P=0.01). Median SUV decrease was 63% (7.5-95.5%) and predicted pCR (P=0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50 days) than those without (P=0.02). Patients with post-CRT SUV<4 had a lower recurrence compared with those without (P=0.03). Patients with SUV decrease≥63% had improved overall survival at median follow-up of 40 months than those without (P=0.006). CONCLUSIONS: PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV<4, and SUV decrease≥63% were predictive of recurrence-free and overall survival.

Impact of expression system on the function of the C6.5 diabody PET radiotracer.

The ability of engineered antibodies to rapidly and selectively target tumors that express their target antigen makes them well suited for use as radioimaging tracers. The combination of molecular size and bivalent nature makes diabody molecules a particularly promising structure for use as radiotracers for diagnostic imaging. Previous data have demonstrated that the anti-HER2 C6.5 diabody (C6.5db) is an effective radiotracer in preclinical models of HER2-positive cancer. The aim of this study was to evaluate the impact on radiotracer performance, associated with expressing the C6.5db in the Pichia pastoris (P-C6.5db) system as compared to Escherichia coli (E. C6.5db). Glycosylation of P-C6.5db led to faster blood clearance and lower overall tumor uptake than seen with E. coli-produced C6.5db. However, P-C6.5db achieved high tumor/background ratios that are critical for effective imaging. Dosimetry measurements determined in this study for both (124)I-P-C6.5db and (124)I-E-C6.5db suggest that they are equivalent to other radiotracers currently being administered to patients.

COVID-19 Vaccine-Related Local FDG Uptake.

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.

Multicenter Trial of [18F]fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging of Head and Neck Cancer and Negative Predictive Value and Surgical Impact in the N0 Neck: Results From ACRIN 6685.

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.

Findings of intramediastinal gossypiboma with F-18 FDG PET in a melanoma patient.

FDG PET/CT scan was performed to evaluate recurrence in an asymptomatic 64-year-old man with a history of melanoma in the left posterior ear. PET/CT images showed an intense ring-shaped area of FDG activity in the posterior mediastinum in a large posterior mediastinal mass. However, further evaluation indicated that this activity was caused by an intramediastinal gossypiboma after coronary artery bypass graft surgery 4 years before the PET/CT scan.

Follow-up FDG PET in the evaluation of unexplained focal activity in the abdomen.

PURPOSE: This study assessed the value of a follow-up FDG PET scan when the initial PET demonstrated unexplained findings of focal FDG uptake in the abdomen. METHOD: The records of 3634 patients with PET scans were retrospectively reviewed. Those patients who had follow-up PET scans after the initial PET scan showed unexplained FDG activity in the abdomen were further analyzed. The results from the second PET scan were compared with the follow-up data, which included the findings from other imaging modalities, clinical course, and biopsy or surgical pathology interpretations. RESULTS: A total of 59 patients were included in the final analysis. The average time interval between the initial and the follow-up PET scans was 4.2 + 2.3 months. The follow-up PET provided a clear-cut diagnosis in 55 (93.2%) of these patients, whereas diagnoses in only 4 patients remained indeterminate. Follow-up PET scans were negative for abdominal malignancy in 38 patients. Thirty-five of these 38 patients with negative follow-up PET were proven to be without abdominal malignancy, with a negative predictive value of 92.1% (35 of 38). The follow-up PET was positive in 17 patients. Fifteen of these 17 patients with a positive follow-up PET scans were found to have malignancy in the abdomen with a positive predicative value of 88.2% (15 of 17). All 4 patients with indeterminate follow-up scans were proven not to have malignancy. CONCLUSION: Follow-up FDG PET scan provides an effective means for diagnosing unexplained findings in the abdomen that were previously detected on initial PET scan.

Normal Variants and Pitfalls Encountered in PET Assessment of Gynecologic Malignancies.

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.

ACR-ACNM Practice Parameter for the Performance of Fluorine-18 Fluciclovine-PET/CT for Recurrent Prostate Cancer.

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.

Correlation of molecular response as measured by 18-FDG positron emission tomography with outcome after chemoradiotherapy in patients with esophageal carcinoma.

PURPOSE: To determine whether 18-fluorodeoxyglucose positron emission tomography (PET) computed tomography scans predict the pathologic complete response and disease-free and overall survival in patients with esophageal carcinoma undergoing definitive or preoperative chemoradiotherapy. METHODS AND MATERIALS: The records of patients with esophageal carcinoma presenting for definitive or preoperative treatment and undergoing pre- and post-treatment 18-fluorodeoxyglucose PET-computed tomography scans were retrospectively reviewed. The histologic type, T stage, and nodal status were the variables investigated to determine a relationship with the baseline standardized uptake value (SUV) of the primary tumor at diagnosis. We also attempted to determine whether a relationship exists between the percent decrease in SUV and a pathologic complete response, overall and disease-free survival. RESULTS: A total of 81 patients, 14 women and 67 men, underwent 18-fluorodeoxyglucose PET-computed tomography scanning before treatment and 63 also had post-treatment scans. T stage and tumor location predicted in univariate, but not multivariate, analysis for the initial SUV. Of the patients with a postchemoradiotherapy SUV of <2.5, 66% had tumor in the surgical specimen and 64% of patients had positive lymph nodes at surgery that were not imaged on the postchemoradiotherapy PET scan. A trend existed for post-treatment SUV and the days from radiotherapy to surgery to predict for a pathologic complete response (p = 0.09 and p = 0.08, respectively). The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group (p = 0.01). CONCLUSIONS: A correlation was found between the depth of tumor invasion and the baseline SUV. The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group. Caution should be exercised in using post-treatment PET scans to determine the necessity for surgical resection.

The effects of estrogen, progesterone, and C-erbB-2 receptor states on 18F-FDG uptake of primary breast cancer lesions.

UNLABELLED: The purpose of this prospective study was to investigate whether correlations exist between 18F-FDG uptake of primary breast cancer lesions and predictive and prognostic factors such as estrogen receptor (ER), progesterone receptor (PR), and C-erbB-2 receptor (C-erbB-2R) states. METHODS: Before undergoing partial or total mastectomy, 213 patients with newly diagnosed breast cancer underwent 18F-FDG PET (5.2 MBq/kg of body weight). The maximum standardized uptake value (SUV) of the primary lesion was measured in each patient. Standard immunohistochemistry was performed on a surgical specimen of the cancer lesion to characterize the receptor state of the tumor cells. Pearson chi2 tests were performed on the cross-tables of different receptor states to test any association that may exist among ER, PR, and C-erbB-2R. Maximum SUV measurements for different receptor states were compared using factorial ANOVA in a completely random design. RESULTS: After exclusion of certain lesions, 118 lesions were analyzed for this study. The mean maximum SUVs of ER-positive and ER-negative lesions were 3.03 +/- 0.26 and 5.64 +/- 0.75, whereas those of PR were 3.24 +/- 0.29 and 4.89 +/- 0.67, respectively, and those of C-erbB-2R were 4.64 +/- 0.70 and 3.70 +/- 0.35, respectively. Chi2 tests for ER and PR showed that if one is positive then the other tends to be positive as well (chi2 = 71.054, P < 0.01). For ER and C-erbB-2R states, if ER is positive, C-erbB-2R will more likely be negative (chi2 = 13.026, P < 0.01). No relationship was detected between PR and C-erbB-2R states (chi2 = 3.695, P > 0.05). ANOVAs showed that PR state alone (F = 0.095, P > 0.05) and C-erbB-2R state alone (F = 0.097, P > 0.05) had no effect on 18F-FDG uptake but ER state alone had an effect (F = 9.126, P < 0.01). ER and PR being together had no additional effect on 18F-FDG uptake. Our study also demonstrated that interactions exist between ER and C-erbB-2R state and between PR and C-erbB-2R state. CONCLUSION: SUV measurements may provide valuable information about the state of ER, PR, and C-erbB-2R and the associated glucose metabolism as measured by 18F-FDG uptake of the primary breast cancer lesions. Such an association may be of importance to treatment planning and outcome in these patients.

Dual-time point FDG PET imaging in the evaluation of pulmonary nodules with minimally increased metabolic activity.

PURPOSE: FDG PET has high accuracy in the evaluation of lung nodules. A standardized uptake value (SUV) > or =2.5 is frequently used as a criterion for malignancy in this setting. However, some malignant nodules have only mild FDG activity with a SUV less than 2.5. Assessment of the etiology of lung nodules with only mild metabolic activity remains difficult. This study was undertaken to compare the accuracy of dual-time point and standard single-time FDG PET imaging in the evaluation of such lung nodules. METHODS: Four hundred fifty-seven dual-time FDG PET scans for lung nodules were retrospectively analyzed. Among them, 46 met the selection criteria and were included for the final analysis. Five methods of interpreting FDG PET results were compared. These methods included visual analysis for both initial and delayed images; SUV analysis for both initial and delayed images in which a SUV of 2.5 is regarded as criteria for malignancy; and finally, the retention index analysis in which a 10% increase in SUV on the delayed images was regarded as an indication of malignancy. RESULTS: The lowest accuracies came from the visual and single SUV analysis on the initial images. The visual and single SUV analyses on the delayed images produced increased accuracy. The highest accuracy (84.8%) was obtained when a retention index of more than 10% was used as criteria for malignancy. CONCLUSION: Dual-time FDG PET imaging has the potential for improving accuracy of a test in the evaluation of lung nodules with only borderline levels of increased metabolic activity.

Lymphoma Causing Gastrosplenic Fistula Revealed by FDG PET/CT.

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.

Cerenkov Luminescence Imaging as a Modality to Evaluate Antibody-Based PET Radiotracers.

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.