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VPAC1 receptors for imaging breast cancer: a feasibility study.

ABSTRACT: VPAC1 encodes G-protein-coupled receptors expressed on all breast cancer (BC) cells at the onset of the disease, but not on benign lesions. Our extensive preclinical studies have shown that (64)Cu-TP3805 has a high affinity for VPAC1, is stable in vivo, and has the ability to distinguish spontaneously grown malignant BC masses from benign lesions. Our long-term goal is to develop (64)Cu-TP3805 as an agent to perform in vivo histology, to distinguish malignant lesions from benign masses noninvasively and thereby avoid patient morbidity and the excess economic costs of benign biopsies.(18)F-FDG obtained commercially served as a control. (64)Cu-TP3805 was prepared using a sterile kit containing 20 μg of TP3805. Radiochemical purity and sterility were examined. Nineteen consenting women with histologically proven BC were given 370 MBq of (18)F-FDG. One hour later, 6 of these patients were imaged with PET/CT and 13 with positron emission mammography (PEM). Two to 7 d later, 6 PET/CT patients received 111 MBq (± 10%) (n = 2), 127 MBq (± 10%) (n = 2), or 148 MBq (± 10%) (n = 2) of (64)Cu-TP3805 and were imaged 2 and 4 h later. Thirteen PEM patients received 148 MBq (± 10%) of (64)Cu-TP3805 and were imaged 15 min, 1 h, 2 h, and 4 h later. Standardized uptake value (SUV) was calculated for PET/CT patients, and PUV/BGV (PEM uptake value/background value) was calculated for PEM patients. Tumor volume was also calculated.The radiochemical purity of (64)Cu-TP3805 was 97% ± 2%, and specific activity was 44.4 GBq (1.2 Ci)/μmol. In 19 patients, a total of 24 lesions were imaged (15 invasive ductal carcinoma, 1 high-grade mammary carcinoma, 3 lobular carcinoma, 1 invasive papilloma, and 4 sentinel lymph nodes). All lesions were unequivocally detected by (64)Cu-TP3805 and by (18)F-FDG. The average tumor volume as determined by PET/CT with (64)Cu-TP3805 was 90.6% ± 16.1% of that with (18)F-FDG PET/CT, and the average SUV was 92% ± 26.4% of that with (18)F-FDG. For PEM, the tumor volume with (64)Cu-TP3805 was 113% ± 37% of that with (18)F-FDG and the PUV/BGV ratio was 97.7% ± 24.5% of that with (18)F-FDG.(64)Cu-TP3805 is worthy of further investigation in patients requiring biopsy of suggestive imaging findings, to further evaluate its ability to distinguish malignant lesions from benign masses noninvasively.

SUBMITTER: Thakur ML

PROVIDER: S-EPMC5506835 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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Project description:PurposeTo prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM).Materials and methodsInformed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 microg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively.ResultsLymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 microg. When indocyanine green dosages were 10 microg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 microg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore.ConclusionNIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.

Project description:BackgroundBreast cancer surgery results in numerous acute and long-term adverse outcomes; the degree to which these can be mitigated or prevented through prehabilitation is unknown.MethodsWe conducted a longitudinal, single-arm, mixed-methods study to examine the feasibility of prehabilitation in 22 women undergoing breast cancer surgery. All participants received an individualized exercise prescription including upper quadrant-specific resistance and mobility training and aerobic exercise for the duration of their surgical wait time. Feasibility was assessed by recruitment, adherence, attrition, and intervention-related adverse event rates. An exploratory investigation of intervention efficacy was conducted via a 6-min walk test, upper-quadrant strength and range of motion, volumetric chances associated with lymphedema, and participant-reported quality of life, fatigue, pain, and disability. Outcome assessments were conducted at baseline, prior to surgery, and at six and 12 weeks after surgery. Semi-structured interviews with a subset of participants (n = 5) and health-care providers (H; n = 2) were conducted to provide further insights about intervention feasibility. Qualitative data were analyzed using a hybrid inductive and deductive thematic analysis approach.ResultsRecruitment and attrition rates were 62 and 36%, respectively. Average prehabilitation duration was 31 days (range = 7-69 days). Seventy six percent of participants complied with at least 70% of their prehabilitation prescription. There was a clinically significant increase in the 6-min walk distance from baseline to the preoperative assessment (57 m, 95% CI = -7.52, 121.7). The interviews revealed that the intervention was favorably received by participants and HCPs and included suggestions that prehabilitation (i) should be offered to all surgical candidates, (ii) is an avenue to regain control in the preoperative period, (iii) is a facilitator of postoperative recovery, and (iv) is an opportunity to provide education regarding postoperative rehabilitation protocols. A preference for multimodal prehabilitation (including dietetic and psychological counseling) was also highlighted.ConclusionOur findings suggest that surgical prehabilitation in women with breast cancer is feasible. Data are hampered by study sample size and lack of a control group. Thus, randomized controlled trials to examine prehabilitation efficacy in people with breast cancer, especially interventions employing a multimodal strategy, are warranted.

Project description:BackgroundAcceptability and tolerance of chemotherapy on patients treated for breast cancer remain challenging. Complementary approaches such as hypnosis may have a favorable impact both at the time of announcing and during chemotherapy, due to the notorious anxiety, distress, and self-perceived dysfunction. The objective of the study was that the patients complied with at least four self-hypnosis sessions out of the six cycles of chemotherapy.MethodsThis open, prospective longitudinal study assessed feasibility of compliance to self-hypnosis during chemotherapy in an outpatients setting. Training sessions were given by a hypnotherapist. Throughout each cycle of chemotherapy, the patient had to use self-hypnosis to better control her anxiety or any difficulties. Nurses could offer help to the patient. Chemotherapy-associated side effects were evaluated through the NCI-Common Toxicity Criteria for Adverse Events v 4.03; moreover, side effects as pain, nausea, vomiting, fatigue, and anxiety were also evaluated during chemotherapy using a visual analogic scale. Health-related quality of life, emotional distress (anxiety and depression), and cancer-related fatigue were assessed (at inclusion, end of chemotherapy and 3 months later) using the EORTC QLQ-C30 and QLQ-BR23, HADS and MFI-20 questionnaires, respectively. The number of patients screened and actually included in the study was reported, as the reasons for refusal.ResultsThirty-five patients were included with a median age of 55 years (35-78). All patients received a hypnosis training session. The overall compliance with self-hypnosis was 68.6% (95% CI: 50.7%-83.2%), meaning that more than two thirds of patients performed at least four sessions of self-hypnosis. According to NCI-CTCAE, Grade 2 nausea and vomiting was observed in 45.7% and 22.9%, respectively, Grade 2 fatigue in 62.9%. Based on the HADS questionnaire, anxiety increased at the end of the chemotherapy and returned to the initial value 3 months later (p = .97) whereas depression significantly decrease 3 months after the end of chemotherapy with respect to the inclusion (p = .003). Role, emotional, and cognitive functioning were slightly affected throughout the treatment, in contrast to dyspnea or physical functioning.ConclusionOur study showed that self-hypnosis was feasible on patients newly diagnosed for breast cancer receiving chemotherapy.

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VPAC1 receptors for imaging breast cancer: a feasibility study.

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