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14 p.-6 fig.1 tab., Triple-negative breast cancer (TNBC) is characterized by aggressiveness and high rates of metastasis. The identification of relevant biomarkers is crucial to improve outcomes for TNBC patients. Membrane type 1-matrix metalloproteinase (MT1-MMP) could be a good candidate because its expression has been reported to correlate with tumor malignancy, progression and metastasis. Moreover, single-domain variable regions (VHHs or Nanobodies) derived from camelid heavy-chain-only antibodies have demonstrated improvements in tissue penetration and blood clearance, important characteristics for cancer imaging. Here, we have developed a nanobody-based PET imaging strategy for TNBC detection that targets MT1-MMP. A llama-derived library was screened against the catalytic domain of MT1-MMP and a panel of specific nanobodies were identified. After a deep characterization, two nanobodies were selected to be labeled with gallium-68 (68Ga). ImmunoPET imaging with both ([68Ga]Ga-NOTA-3TPA14 and [68Ga]Ga-NOTA-3CMP75) in a TNBC mouse model showed precise tumor-targeting capacity in vivo with high signal-to-background ratios. (68Ga)Ga-NOTA-3CMP75 exhibited higher tumor uptake compared to (68Ga)Ga-NOTA-3TPA14. Furthermore, imaging data correlated perfectly with the immunohistochemistry staining results. In conclusion, we found a promising candidate for nanobody-based PET imaging to be further investigated as a diagnostic tool in TNBC., This research was supported by BBVA Foundation grants for Scientific Research Teams: “Imaging of triple-negative breast cancer with specific miniaturized antibodies by ImmunoPET (BREIMPET)” Ref.:PR[17]_BIO_IMG_0114 (2017) and “Radioinmunotheragnostics for metastatic lung cancer with pretargeted clickable Ab Fragments (TherAbnostic)” Ref.: PR[19]_BIO_IMG_0096. (2020).

Introduction Total pancreatectomy (TP) is an uncommon operation, with indications that have not been clearly defined and non-standardized postoperative results. We present a national multicentric study on TP and a comparison with the existing literature. Methods A prospective observational study using data from the national registry of patients after pancreaticoduodenectomy and TP performed for any indication during the study period: January 1–December 31, 2015. Results 1016 patients were included from 73 hospitals, 112 of whom had undergone TP. The percentage of TP from the total number of cases was 11%. The mean age was 63.5 years, and 57.2% were males. The most frequently suspected radiological diagnosis was pancreatic cancer (58/112 cases). The most common TP technique was “mesentery artery first” (43/112 cases). Venous resections were performed in 23 patients (20.5%). The percentage of postoperative complications within 90 days was 50%, but major complications (>IIIA) were only 20.7%. The overall 90-day mortality was 8% (9 patients). The average stay was 20.7 days. The 3 most frequent definitive histological diagnoses were: adenocarcinoma of the pancreas, intraductal papillary mucinous neoplasm and chronic pancreatitis. The R0 rate was 67.8%. Conclusions This study shows that the morbidity and mortality results of TP in Spain are similar or superior to previous publications. More precise TP studies are necessary, focused on specific complications such as endocrine insufficiency.

Resumen Introduccion La pancreatectomia total (PT) es una intervencion infrecuente, con unas indicaciones no claramente definidas y unos resultados postoperatorios no estandarizados. Presentamos un estudio multicentrico nacional sobre PT y una comparacion con la literatura existente. Metodos Estudio prospectivo observacional realizado mediante el registro nacional de pacientes operados de duodenopancreatectomia cefalica y PT realizadas por cualquier indicacion durante el periodo comprendido entre el 1 enero y el 31 diciembre del 2015. Resultados Se incluyo a 1.016 pacientes, pertenecientes a 73 centros; de ellos, 112 correspondian a PT. El porcentaje de PT/numero total de casos es del 11%. La edad media fue 63,5 anos y eran varones un 57,2%. El diagnostico radiologico de sospecha mas frecuente fue cancer de pancreas (58/112 casos). La tecnica de la PT mas habitual fue «arteria mesenterica primero» (43/112 casos). Se efectuaron resecciones venosas en 23 pacientes (20,5%). El porcentaje de complicaciones postoperatorias a 90 dias fue 50%, pero las complicaciones mayores (> IIIA) solo el 20,7%. La mortalidad global a 90 dias fue del 8% (9 pacientes). La estancia media fue 20,7 dias. Los 3 diagnosticos histologicos definitivos mas frecuentes fueron: adenocarcinoma de pancreas, neoplasia mucinosa papilar intraductal y pancreatitis cronica. La tasa de R0 fue del 67,8%. Conclusiones Este estudio demuestra que los resultados de morbimortalidad de la PT en Espana son similares o superiores a los publicados previamente. Es necesario un estudio mas especifico sobre PT centrado en complicaciones especificas, como la insuficiencia endocrina.

(68)Ga-DOTA-peptides are a promising PET radiotracers used in the detection of different tumours types due to their ability for binding specifically receptors overexpressed in these. Furthermore, (68)Ga can be produced by a (68)Ge/(68)Ga generator on site which is a very good alternative to cyclotron-based PET isotopes. Here, we describe a manual labelling approach for the synthesis of (68)Ga-labelled DOTA-peptides based on concentration and purification of the commercial (68)Ga/(68)Ga generator eluate using an anion exchange-cartridge. (68)Ga-DOTA-TATE was used to image a pheochromocytoma xenograft mouse model by a microPET/CT scanner. The method described provides satisfactory results, allowing the subsequent (68)Ga use to label DOTA-peptides. The simplicity of the method along with its implementation reduced cost, makes it useful in preclinical PET studies.