A research report submitted to the Faculty of Health Sciences, University of Witwatersrand, in fulfillment of the requirements for the degree of Master of Medicine in the branch of Internal Medicine Johannesburg, 2015 / Lymphadenopathy is a common clinical presentation of disease in South Africa (SA), particularly in the era of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) coinfection. Methods Data from 560 lymph node biopsy reports of specimens from patients older than 12 years at Chris Hani Baragwanath Academic Hospital (CHBAH) between 1 January 2010 and 31 December 2012 was extracted from the National Health Laboratory Service (NHLS), division of Anatomical Pathology. Cytology reports of lymph node fine needle aspirates (FNAs) performed prior to lymph node biopsy in 203 patients were also extracted from the NHLS. Consent was not obtained from participants for their records to be used as patient information was anonymized and de-identified prior to analysis. Results The majority of patients were female (55%) and of the African/black racial group (90%). The median age of patients was 40 years (range12-94). The most common indication for biopsy was an uncertain diagnosis (more than two differential diagnoses entertained), followed by a suspicion for lymphoma, carcinoma and TB. Overall, malignancy constituted the largest biopsy pathology group (39%), with 36% of this group being carcinoma and 27% non-Hodgkin lymphoma. 22% of the total sampled nodes displayed necrotizing granulomatous inflammation (including histopathology and cytology demonstrating definite, and suspicious for mycobacterial infection), 8% comprised HIV reactive nodes; in the remainder no specific pathology was identified (nonspecific reactive lymphoid hyperplasia). Kaposi sarcoma (KS) accounted for 3% of lymph node pathology in this sample. Concomitant lymph node pathology was diagnosed in four cases of nodal KS (29% of the subset). The co-existing pathologies were TB and Castleman disease. HIV-positive patients constituted 49% of this study sample and the majority (64%) of this subset had CD4 counts less than 350 cells/ul. 27% were HIVnegative and in the remaining nodes, the HIV status of patients was unknown. The most common lymph node pathologies in HIV-positive patients were Mycobacterial infection (31%), HIV reactive nodes (15%), non-Hodgkin lymphoma (15%) and nonspecific reactive lymphoid hyperplasia (15%). Only 9% were of Hodgkin lymphoma. In contrast, the most common lymph node pathologies in HIV-negative patients were nonspecific reactive lymphoid hyperplasia (45%), carcinoma (25%) and Mycobacterial infection (11%). In this group, non-Hodgkin lymphoma and Hodgkin lymphoma constituted 9% and 8%, respectively. There were more cases of high-grade non-Hodgkin lymphoma in the HIV-positive group compared to the HIV-negative group. FNA and lymph node biopsy had excellent agreement with regard to Hodgkin lymphoma (K 0.774, SE 0.07, 95% CI 0.606-0.882, p=0.001), and good agreement with regard to non-Hodgkin lymphoma (K 0.640, SE 0.07, 95% CI 0.472-0.807, p=0.001), carcinoma (K 0.723, SE 0.069, 95% CI 0.528-0.918, p=0.001), and mycobacterial infection (K 0.726, SE 0.07, 95% CI 0.618-0.833, p=0.001). Conclusions The most common lymph node pathologies in CHBAH are malignancies, nonspecific reactive lymphoid hyperplasia, necrotizing granulomatous inflammation and HIV reactive nodes. The distribution of disease differed in HIV-positive patients. Overall, adequate FNA samples of lymph nodes have been found to have good correlation with lymph node biopsy findings in our setting.

Orientador: Antônio José Maria Cataneo / Resumo: Introdução: No melanoma primário, a aplicabilidade da biópsia de linfonodo sentinela (BLS), seguida ou não de esvazimento linfonodal (EL) é conhecida. Na recidiva locorregional (RL) de melanoma, alguns serviços tendem a indicá-la, buscando estadiamento mais acurado para embasar condutas individualizadas aos pacientes, ainda que as evidências sejam insuficientes. Objetivo: Avaliar o sucesso da BLS no encontro do linfonodo sentinela (LNS) e sua positividade na RL. Comparar a sobrevida entre os pacientes com LNS positivo e negativo. Verificar diferença na sobrevida pós EL. Métodos: Revisão sistemática, através das bases MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE e CENTRAL, buscando estudos experimentais e observacionais sobre BLS na RL de melanoma. Desfechos avaliados: sucesso na BLS pelo encontro do LNS, positividade para melanoma no LNS; sobrevida no subgrupo LNS positivo comparado com o negativo; sobrevida livre de doença no subgrupo LNS positivo comparada com o negativo; sobrevida dos pacientes submetidos ao EL. Para metanálises, utilizaram-se RevMan 5.3 e StatsDirect 3.0.121. Resultados: Foram identificados 1872 estudos, destes, seis estudos observacionais foram incluídos, totalizando 449 pacientes. O LNS foi encontrado em 98% das BLS (IC 95-100%, I2=53,7% - seis estudos). LNS com 32% de positividade para melanoma (IC 19-47%, I2= 84,6% - seis estudos). A chance de sobrevida global em cinco anos foi 2,49 vezes maior no subgrupo com LNS negativo (IC 95% 1,41-4,38, I2=0% - qua... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: In primary melanoma, the applicability of sentinel lymph node biopsy (SLB), followed or not by complete lymph node dissection (CLND) is known. In locoregional recurrence (LR) of melanoma, some groups may indicate it for more accurate staging to support individualized management, even with scarce evidence. Objective: To evaluate success in SLB and its positivity in LR. Compare survival between patients with positive and negative sentinel lymph node (SLN). Check for survival modification after CLND. Methods: Systematic review through databases such as MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE and CENTRAL, searching for experimental and observational studies on SLB in melanoma LR. Outcomes assessed: success in SLB by finding the SLN, positivity for melanoma in the SLN; survival in the positive SLN subgroup compared to the negative one; disease-free survival in the positive versus negative SLN subgroup; survival of patients undergoing CLND. For meta-analyzes, RevMan 5.3 and StatsDirect 3.0.121 were used. Results: The total number of patients in six observational studies was 449, over 1872 studies indentified. The SNL was found in 98% of SLB (95-100% CI, I2 = 53.7%, 6 studies). SLB detected 32% positivity for melanoma on SNL (CI 19-47%, I2 = 84.6%, 6 studies). The chance of five year overall survival was 2,49 higher in the negative SNL subgroup (95% CI 1.41-4.38, I2 = 0%, 4 studies). Meta-analyzes were not performed due to lack of objective data for disease-free survi... (Complete abstract click electronic access below) / Doutor

Staging is critical in the management of cancer. Sentinel lymph node (SLN) biopsy is one method used in the assessment of cancer spread. SLN procedures are standard practice in the management of some cancers although; these procedures have only recently been developed and refined. SLN procedures are commonly used in the management of melanomas and breast cancers in patients with no evidence of metastatic disease on clinical exam. SLN procedures include detection, localization, and assessment of SLNs. The detection/localization components vary in technique and rates of success. The procedures with the least number of detection/localization techniques generally include the use of blue dye or the use of a radiotracer with intraoperative gamma counting. The most complex procedures involve the use of blue dye, the use of a radiotracer with preoperative gamma imaging and preoperative gamma counting, intraoperative gamma counting, or some combination of these techniques. The ideal procedure for SLN would include all the listed techniques however; all facilities do not incorporate the most complete procedure, for different reasons. An investigation using a small FOV (5 in x 5 in) gamma camera intraoperatively for SLN procedures in melanoma and breast cancer patients was performed. A smaller FOV camera is capable of obtaining some of the same information as a conventional gamma camera. It is possible that centers, which do not or are not able to take advantage of preoperative imaging, may find the use of a smaller FOV gamma camera in the operating room useful. The investigation consisted of a total of 41 patients; it was split into two studies, Study 1: melanoma and study 2: breast cancer. The melanoma study found the added use of a smaller FOV camera under the parameters of this study to be minimal. Study 2 was broken into two branches; branch 1: camera/probe/dye and branch 2: probe/dye, for a comparison study. Comparing the two branches did not show the smaller FOV camera to reduce the time spent in the operating room versus using the probe and blue dye.

Indiana University-Purdue University Indianapolis (IUPUI) / Endometrial cancer is the most common gynecologic cancer in the United States, and patients with early-stage endometrioid adenocarcinoma have a favorable prognosis. Over the past decade, the gynecologic oncology community has debated whether potential harms of systematic lymph node dissection (LND) outweigh potential benefits for these patients. To minimize number of nodes removed, sentinel lymph node dissection (SLND) is under investigation as an alternative. However, ongoing uncertainty of LND/SLND best practices may result in variations in disease management and discrepant outcomes. Methods Three retrospective cohort studies examined LND/SLND use in patients with endometrioid adenocarcinoma. Two examined temporal and geographic variations, respectively, utilizing the Surveillance, Epidemiology, and End Results (SEER) 18 dataset for the years 2004 through 2015. The third used the SEER-Medicare dataset from 2003 through 2016 to quantify and compare the risk of developing 6-month post-surgical lymphedema, lymphocele, hemorrhage, ileus, infection, thrombosis, and all-cause death by number of lymph nodes removed (0, 1-4, 5-9, or 10+). Results Time trend analyses found LND increased from 2004 through 2008, followed by a significant decline through 2015. SLND was rare and did not increase significantly. Significant geographic variation existed for LND use but not SLND. Per 1,000 patients, analyses of 6-month post-surgical complications found 6.5 experienced lymphedema, 3.9 experienced lymphocele, 15.7 experienced hemorrhage, 28.7 experienced ileus, 37.1 experienced infection, 18.6 experienced thrombosis, and 19.8 died. Controlling for size of primary tumor, tumor grade, comorbidities, race/ethnicity, age at diagnosis, adjuvant chemotherapy, and radiotherapy, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) showed greater risk for ileus (HR: 1.53; 95% CI: 1.24-1.90), infection (HR: 1.52; 95% CI: 1.25-1.83), and thrombosis (HR: 1.41; 95% CI: 1.09-1.82) when comparing removal of 10+ nodes versus 0 nodes. Conclusion Overall, these studies found significant temporal and geographic variation in LND, as well as increasing risk of post-surgical complications associated with increasing numbers of lymph nodes removed. Should continued research into SLND find strong evidence that it effectively detects cancer spread, patients may benefit through decreased risk of post-surgical ileus, infection, and thrombosis.

O diagnóstico precoce de tumores e metástase constitui atualmente o elemento de maior impacto dentro das políticas de saúde públicas contra o câncer. No câncer de mama e melanoma, a técnica de biópsia de linfonodo sentinela, para o diagnostico de metástase, tem sido muito utilizada evitando a dissecção total dos nodos da região anatômica afetada, e permitindo definir com precisão o procedimento terapêutico a utilizar. O objetivo principal deste trabalho centrou-se no desenvolvimento de conjugados radiomarcados de dextran-manose para diagnóstico, utilizando o núcleo de tecnécio altamente estável, [99mTc(CO)3]+. A cisteína, ligante tridentado, foi incorporada na estrutura dos conjugados, como agente quelante do Tecnécio-99m. As condições de marcação definidas para os produtos avaliados garantiram altos valores de pureza radioquímica (>90%) e atividade específica (>59,9 MBq/nmol) assim como uma alta estabilidade in vitro. Os conjugados de dextran-cisteína-manose demonstraram uma captação superior (4 vezes maior) nos nodos linfáticos em relação aos homólogos que não possuíam manose na estrutura. O conjugado de dextran-cisteína-manose de 30 kDa radiomarcado (99mTc-DCM2) foi o traçador com melhor desempenho biológico entre os avaliados à diferentes atividades injetadas. Demonstrou-se que concentrações superiores a 1 M favorecem a retenção do produto nos nodos linfáticos. As comparações com radiofármacos já utilizados no Brasil (Dextran-500 e Fitato) para detecção de linfonodo sentinela evidenciaram a superioridade do 99mTc-DCM2. / Early diagnosis of tumors and metastasis is the current cornerstone in public health policies directed towards the fights against cancer. In breast cancer and melanoma, the sentinel lymph node biopsy has been widely used for diagnoses of metastasis. The minor impact in patient of this technique compared with total nodes dissection and the accurate definition of therapeutic strategies have powered its spreading. The aim of this work was the development of radiolabeled dextran-mannose conjugates for diagnosis using the stable technetium core [99mTc(CO)3]+. Cysteine, a trident ligand, was attached to the conjugates backbone, as a chelate for 99mTc labeling. Radiolabeling conditions established for all products considered in this study showed high radiochemical purities (> 90%) and specific activities (>59,9 MBq/nmol) as well and high stability obtained through in vitro tests. The lymphatic node uptake increased significantly (4-folds) when mannose units were added to the conjugates compared with those without this monosaccharide. The radiolabeled cysteine-mannose-dextran conjugate with 30 kDa (99mTc-DCM2) showed the best performance at different injected activities among the studied tracers. Concentrations of this radiocomplex higher than 1 M demonstrated an improvement of lymph node uptakes. Comparisons of 99mTc-DCM2 performance with commercial radiopharmaceuticals in Brazil market for lymph node detection showed its upper profile.

O diagnóstico precoce de tumores e metástase constitui atualmente o elemento de maior impacto dentro das políticas de saúde públicas contra o câncer. No câncer de mama e melanoma, a técnica de biópsia de linfonodo sentinela, para o diagnostico de metástase, tem sido muito utilizada evitando a dissecção total dos nodos da região anatômica afetada, e permitindo definir com precisão o procedimento terapêutico a utilizar. O objetivo principal deste trabalho centrou-se no desenvolvimento de conjugados radiomarcados de dextran-manose para diagnóstico, utilizando o núcleo de tecnécio altamente estável, [99mTc(CO)3]+. A cisteína, ligante tridentado, foi incorporada na estrutura dos conjugados, como agente quelante do Tecnécio-99m. As condições de marcação definidas para os produtos avaliados garantiram altos valores de pureza radioquímica (>90%) e atividade específica (>59,9 MBq/nmol) assim como uma alta estabilidade in vitro. Os conjugados de dextran-cisteína-manose demonstraram uma captação superior (4 vezes maior) nos nodos linfáticos em relação aos homólogos que não possuíam manose na estrutura. O conjugado de dextran-cisteína-manose de 30 kDa radiomarcado (99mTc-DCM2) foi o traçador com melhor desempenho biológico entre os avaliados à diferentes atividades injetadas. Demonstrou-se que concentrações superiores a 1 M favorecem a retenção do produto nos nodos linfáticos. As comparações com radiofármacos já utilizados no Brasil (Dextran-500 e Fitato) para detecção de linfonodo sentinela evidenciaram a superioridade do 99mTc-DCM2. / Early diagnosis of tumors and metastasis is the current cornerstone in public health policies directed towards the fights against cancer. In breast cancer and melanoma, the sentinel lymph node biopsy has been widely used for diagnoses of metastasis. The minor impact in patient of this technique compared with total nodes dissection and the accurate definition of therapeutic strategies have powered its spreading. The aim of this work was the development of radiolabeled dextran-mannose conjugates for diagnosis using the stable technetium core [99mTc(CO)3]+. Cysteine, a trident ligand, was attached to the conjugates backbone, as a chelate for 99mTc labeling. Radiolabeling conditions established for all products considered in this study showed high radiochemical purities (> 90%) and specific activities (>59,9 MBq/nmol) as well and high stability obtained through in vitro tests. The lymphatic node uptake increased significantly (4-folds) when mannose units were added to the conjugates compared with those without this monosaccharide. The radiolabeled cysteine-mannose-dextran conjugate with 30 kDa (99mTc-DCM2) showed the best performance at different injected activities among the studied tracers. Concentrations of this radiocomplex higher than 1 M demonstrated an improvement of lymph node uptakes. Comparisons of 99mTc-DCM2 performance with commercial radiopharmaceuticals in Brazil market for lymph node detection showed its upper profile.

Objetivos: Avaliar a eficácia da injeção intraoperatória para identificação do linfonodo sentinela (LS) em câncer de mama com o uso do Dextran 500-99m-Tecnécio (Tc) e azul patente. Analisar se as doses do radiofármaco, o IMC (índice de massa corporal) e o volume da mama influenciam no tempo para migração ao LS. Metodologia: Estudo prospectivo, realizado entre abril de 2008 e junho de 2009, que incluiu 74 biópsias de LS em pacientes com câncer de mama em estádios T1N0 e T2N0. Injetou-se, após indução anestésica, de 0,5 a 1,5 mCi de Dextran 500-99m-Tc filtrado 0,22 μm na região subareolar num volume de 5 ml e 2 ml de azul patente. Resultados: Identificou-se o LS em 100% dos casos. Um LS (1,35%) estava marcado apenas com o azul patente. A taxa de identificação com o “probe” foi de 98% (73/74 casos). A dose média de radiofármaco aplicada foi 0,97 mCi + 0,22. O tempo médio para marcação do LS foi de 10,7 minutos (+ 5,7min). Identificamos em média 1,66 LS com o radioisótopo. A dose aplicada não apresentou relação com o tempo para captação (p=0,73). Quanto maior o volume da mama e IMC, maior o tempo para captação na região axilar (Pearson Correlation r=0,393 p<0,01; r=0,469 p<0,01 - respectivamente). Conclusão: A injeção intraoperatória do radiofármaco é eficaz para identificação do LS em câncer de mama. O tempo para marcação do LS é maior em pacientes com IMC elevado e mamas volumosas. Doses maiores de radiofármaco não diminuem o tempo de migração. / Objectives: To determine the identification of sentinel lymph node (SLN) in breast cancer after intraoperative injection of Dextran 500‐99mTechnetium (Tc) and blue dye. To analyze if the doses of the radioisotope, body mass index (BMI) and breast volume influence the migration time of the SLN. Methodology: Prospective study between april 2008 and june 2009, which included 74 biopsies of SLN in patients with breast cancer in stages T1N0 and T2N0. Intraoperative injection after induction of general anesthesia, 0.5 to 1.5 mCi of dextran 500‐99m‐Tc filtered 0.22 μm in the subareolar region in a volume of 5 ml and 2 ml of blue dye. Results: We identified the SLN in 100% of cases. In one case (1.35%) the SLN was marked only with the blue dye. The SLN identification rate with the probe was 98% (73/74 cases). The mean dose of radioisotope injected was 0.97 + 0.22 mCi. The average time to mark the SLN was 10.7 minutes (+ 5.7 min). We identified an average 1.66 SLN with the radioisotope. The dose had no effect on the time to capture (p = 0.73). The larger breast volume and BMI, the greater the capture time in the axillary region (Pearson Correlation r=0.393 p <0.01, r=0.469 p <0.01 - respectively). Conclusion: Intraoperative injection of the radioisotope is effective for the identification the SLN in breast cancer. Time to mark the SLN is higher in patients with high BMI and large breasts. Higher doses of radioisotope do not decrease the migration time.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Objetivos. Desenvolver um modelo experimental para identificaÃÃo de linfonodo sentinela (LS) da mama da cadela com uso de corante azul de metileno e comparÃ-lo com o azul patente, controlados por tecnÃcio. MÃtodos. O trabalho foi realizado em 23 cadelas, tendo-se observado a marcaÃÃo dos LS do primeiro par superior de mamas ao se injetarem 0,2 ml de TecnÃcio 99m ligado ao fitato (Tc 99m) e 0,5 ml de azul patente Guerbet V 2,5 % nos espaÃos subpapilares das mamas direitas e 0,2 ml de Tc-99m e 0,5 ml do azul de metileno 1 % nos mesmos espaÃos das mamas esquerdas. Resultados. Na mama direita, as tÃcnicas de biopsia de LS quando utilizados o Tc-99m e azul patente foram concordantes. Dos 23 LS estudados, somente um nÃo corou nem foi captante. O azul patente foi eficaz em 100 % quando comparado com os dois mÃtodos associados. Na mama esquerda, dos 23 LS estudados, somente dois nÃo coraram e um nÃo foi captante, sendo esta diferenÃa estatisticamente nÃo significante. A tÃcnica de biopsia do LS utilizando-se o azul de metileno apresentou-se com eficÃcia de 91,3 % quando utilizado isoladamente e de 100 % quando associado ao Tc-99m. ConclusÃo. O uso do azul de metileno associado ao radiofÃrmaco pode ser considerado como tÃcnica potencial na pesquisa transoperatÃria do LS das mamas, sendo uma opÃÃo menos onerosa e com menores efeitos alergÃnicos do que o azul patente / Objetivos. Desenvolver um modelo experimental para identificaÃÃo de linfonodo sentinela (LS) da mama da cadela com uso de corante azul de metileno e comparÃ-lo com o azul patente, controlados por tecnÃcio. MÃtodos. O trabalho foi realizado em 23 cadelas, tendo-se observado a marcaÃÃo dos LS do primeiro par superior de mamas ao se injetarem 0,2 ml de TecnÃcio 99m ligado ao fitato (Tc 99m) e 0,5 ml de azul patente Guerbet V 2,5 % nos espaÃos subpapilares das mamas direitas e 0,2 ml de Tc-99m e 0,5 ml do azul de metileno 1 % nos mesmos espaÃos das mamas esquerdas. Resultados. Na mama direita, as tÃcnicas de biopsia de LS quando utilizados o Tc-99m e azul patente foram concordantes. Dos 23 LS estudados, somente um nÃo corou nem foi captante. O azul patente foi eficaz em 100 % quando comparado com os dois mÃtodos associados. Na mama esquerda, dos 23 LS estudados, somente dois nÃo coraram e um nÃo foi captante, sendo esta diferenÃa estatisticamente nÃo significante. A tÃcnica de biopsia do LS utilizando-se o azul de metileno apresentou-se com eficÃcia de 91,3 % quando utilizado isoladamente e de 100 % quando associado ao Tc-99m. ConclusÃo. O uso do azul de metileno associado ao radiofÃrmaco pode ser considerado como tÃcnica potencial na pesquisa transoperatÃria do LS das mamas, sendo uma opÃÃo menos onerosa e com menores efeitos alergÃnicos do que o azul patente / Objectives. To develop an experimental model for identification of sentinel lymph node (SLN) of breast bitch with the use of methylene blue and compares it with the patent blue, both associated with technetium. Methods. 23 dogs, there was the marking of the SLN of the first upper pair of breasts to inject 0.2 ml of Tc-99m phytate bound to (99m) and 0.5 ml of patent blue Guerbet V 2,5 % in subpapilar spaces right breast and 0.2 ml of 99mTc and 0.5 ml of 1% methylene blue in the same spaces left breast. Results. In the right breast biopsy techniques using 99mTc SLN and blue dye are in agreement. Of the 23 SLN studied, only one was not flushed nor uptake. The patent blue was effective in 100% when compared with the two methods together. The left breast of 23 SLN studied, only two non-stained and one was not uptake, this difference was not statistically significant. The SLN biopsy technique using methylene blue appeared with a 91.3% effectiveness when used alone and 100% when associated with 99mTc. Conclusion: The use of methylene blue associated with the radiotracer technique can be considered as potential research intraoperative SLN of breast, suggesting a less costly and less allergenic effects that blue patent. / Objectives. To develop an experimental model for identification of sentinel lymph node (SLN) of breast bitch with the use of methylene blue and compares it with the patent blue, both associated with technetium. Methods. 23 dogs, there was the marking of the SLN of the first upper pair of breasts to inject 0.2 ml of Tc-99m phytate bound to (99m) and 0.5 ml of patent blue Guerbet V 2,5 % in subpapilar spaces right breast and 0.2 ml of 99mTc and 0.5 ml of 1% methylene blue in the same spaces left breast. Results. In the right breast biopsy techniques using 99mTc SLN and blue dye are in agreement. Of the 23 SLN studied, only one was not flushed nor uptake. The patent blue was effective in 100% when compared with the two methods together. The left breast of 23 SLN studied, only two non-stained and one was not uptake, this difference was not statistically significant. The SLN biopsy technique using methylene blue appeared with a 91.3% effectiveness when used alone and 100% when associated with 99mTc. Conclusion: The use of methylene blue associated with the radiotracer technique can be considered as potential research intraoperative SLN of breast, suggesting a less costly and less allergenic effects that blue patent.

Accurate detection of the spread of cancer is critical for planning the best treatment strategy for a patient. Currently, an invasive sentinel lymph node biopsy is commonly used to detect metastases after a primary tumor is detected. This procedure results in patient morbidity, requires weeks of waiting, and is prone to sampling error. This dissertation presents new developments in an emerging biomedical imaging modality – photoacoustic imaging – and their application to improving the detection of metastases in the lymphatic system in a metastatic mouse model of squamous cell carcinoma of the oral cavity. Label-free spectroscopic photoacoustic imaging is demonstrated to detect hypoxia that results from the development of sub-millimeter cancer foci in the lymph node. In order to improve the sensitivity to micrometastases, molecularly-activated plasmonic nanosensers which are targeted to the epidermal growth factor receptor are introduced. The nanosensors are demonstrated to detect metastases consisting of only a few tens of cells. Improvements to spectroscopic photoacoustic imaging are then demonstrated by selecting imaging wavelengths based on the spectral properties of the optical absorbers. Finally, a new contrast agent – silica-coated gold nanoplates – are used to map the sentinel lymph node with high contrast. The final result is a set of tools that can be used to noninvasively detect micrometastases and improve molecular photoacoustic imaging. / text

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.