Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive 99mTc-labeling for SPECT imaging and radioguided surgery in prostate cancer.

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be -2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

Cirugía radioguíada con análogos de somatostatina radiomarcados en tumores neuroendocrinos: reporte de caso / Radioguided surgery with radiolabeled somatostatin analogues in neuroendocrine tumors: Case report

Resumen Introducción: El mejor tratamiento para los tumores neuroendocrinos es la resección completa del tumor, los ganglios, e inclusive en casos seleccionados, las metástasis a distancia. En ocasiones, el tumor primario es pequeño y de difícil localización preoperatoria o sus recaídas pueden ser difíciles de localizar en el terreno de fibrosis por cirugías o tratamientos previos. La cirugía radioguíada ofrece una opción adicional de localización intraoperatoria que hasta ahora no ha sido muy utilizada en tumores neuroendocrinos. Presentación del caso: Paciente de 59 años con antecedente de resección atípica de duodeno y páncreas por tumor neuroendocrino grado 2 del duodeno un año antes. En la tomografía por emisión de positrones/tomografía computarizada (PET/CT) 68Ga-DOTANOC se encontró un ganglio con sobreexpresión de receptores de somatostatina en el mesenterio, sin otras lesiones a distancia. Por los antecedentes quirúrgicos y la dificultad de visualizar la lesión en las imágenes anatómicas (resonancia magnética [RM]) se decidió realizar la cirugía radioguíada. En el preoperatorio se administraron 15 mCi de tecnecio 99 metaestable-hidrazinonicotinilo-Tyr3-octreotida (99mTc-HYNIC-TOC) y se verificó la buena captación en el ganglio. En cirugía, luego de la disección inicial se utilizó la sonda gamma, que detectó una actividad 5 veces mayor en el ganglio, comparado con los tejidos vecinos, lo que permitió su localización y resección. La evolución fue adecuada y un año después no hay evidencia de recaídas. Conclusión: La cirugía radioguíada no ha sido muy utilizada en la localización intraoperatoria de tumores neuroendocrinos, pero es una buena alternativa en casos seleccionados, como el presentado en este artículo, y permite la detección intraoperatoria y su resección completa.

Abstract Introduction: The best treatment for neuroendocrine tumors is complete resection of the tumor, lymph nodes, and even distant metastases in selected cases. Sometimes, the primary tumor is small and difficult to detect before surgery, or its relapses may be difficult to locate in the fibrosis field due to previous surgeries or treatments. Although radioguided surgery allows for additional intraoperative localization, it has yet to be widely used in neuroendocrine tumors. Case report: A 59-year-old patient with a history of atypical resection of duodenum and pancreas due to grade 2 neuroendocrine tumor of the duodenum one year earlier. On 68Ga-DOTANOC PET/CT, a node with somatostatin receptor overexpression was found in the mesentery, with no other distant lesions. Due to the surgical history and the difficulty in visualizing the lesion on anatomical images (MRI), it was decided to perform the radioguided surgery. During the preoperative period, 15 mCi of 99mTc-HYNIC-TOC were administered verifying good uptake in the ganglion. Following the initial dissection, a gamma probe was used, detecting 5 times more activity in the ganglion than in adjacent tissues, allowing for localization and resection. The patient's progress was satisfactory, and one year later there is no evidence of relapse. Conclusion: Although radioguided surgery is not commonly used in the intraoperative location of neuroendocrine tumors, it is a viable option in some situations, such as the one presented here, because it allows for intraoperative detection and full resection.

Use of radioguided surgery technique for the treatment of thyroid cancer recurrence: clinical, surgical and anatomopathological aspects

Introduction: Surgery is the treatment of choice in locoregional thyroid neoplasia recurrence. The intense tissue healing process observed after surgery changes the neck anatomy, makes reoperation difficult, and interferes with surgical success. The use of the Radioguided Occult Lesion Localization (ROLL) technique has become a viable option to localize thyroid tumors. Objective: To analyze the use of the ROLL technique for the treatment of thyroid cancer recurrence with respect to its clinical, surgical and anatomopathological aspects. Methods: A descriptive cross-sectional study that analyzed 56 medical records and anatomopathological examinations of patients of both sexes who had thyroid neoplasms, underwent previous surgeries on this topography, and were submitted to the ROLL technique for recurrence removal from March 2011 to March 2019. Results: Most patients were women aged 46.05 years, on average. Papillary thyroid neoplasm was the most prevalent histological finding. In 100% of the cases, application of the ROLL technique identified and removed the lesions marked with suspicion for malignancy. Conclusion: Radioguided surgery has proved to be a very effective and safe tool to assist with lesion localization for the treatment of thyroid cancer recurrence. This technique has brought no additional side effects to patients, required minimal radiation and made surgery less invasive, reducing postoperative complication rates.

A new method for intraoperative localization of epilepsy focus by means of a gamma probe / Um novo método para a localização intraoperatória de foco de epilepsia mediante utilização de gamaprobe

Objective To evaluate the utility of a new multimodal image-guided intervention technique to detect epileptogenic areas with a gamma probe as compared with intraoperative electrocorticography. Materials and Methods Two symptomatic patients with refractory epilepsy underwent magnetic resonance imaging, videoelectroencephalography, brain SPECT scan, neuropsychological evaluation and were submitted to gamma probe-assisted surgery. Results In patient 1, maximum radioactive count was initially observed on the temporal gyrus at about 3.5 cm posteriorly to the tip of the left temporal lobe. After corticotomy, the gamma probe indicated maximum count at the head of the hippocampus, in agreement with the findings of intraoperative electrocorticography. In patient 2, maximum count was observed in the occipital region at the transition between the temporal and parietal lobes (right hemisphere). During the surgery, the area of epileptogenic activity mapped at electrocorticography was also delimited, demarcated, and compared with the gamma probe findings. After lesionectomy, new radioactive counts were performed both in the patients and on the surgical specimens (ex-vivo). Conclusion The comparison between intraoperative electrocorticography and gamma probe-assisted surgery showed similarity of both methods. The advantages of gamma probe include: noninvasiveness, low cost and capacity to demonstrate decrease in the radioactive activity at the site of excision after lesionectomy. .

Objetivo Avaliar a utilidade de um novo método de intervenção multimodal guiado por imagem, permitindo a detecção de áreas epileptogênicas mediante utilização de gamaprobe em comparação à eletrocorticografia intraoperatória. Materiais e Métodos Dois pacientes sintomáticos com epilepsia refratária realizaram ressonância magnética, videoeletroencefalograma, SPECT cerebral, avaliação neuropsicológica e foram submetidos a neurocirurgia usando gamaprobe. Resultados No paciente 1 as contagens radioativas inicialmente estavam no máximo no giro temporal, cerca de 3,5 cm posterior à ponta do lobo temporal esquerdo. Após corticotomia, o gamaprobe apontou o ponto máximo na cabeça do hipocampo, de acordo com os achados de eletrocorticografia intraoperatória. No paciente 2 as contagens foram máximas na região occipital em sua transição com os lobos temporal e parietal (hemisfério direito). Na cirurgia, a área mapeada da atividade epileptogênica na eletrocorticografia foi também delimitada, demarcada e comparada aos dados do gamaprobe. Após a lesionectomia, procedeu-se uma nova radiocontagem no paciente e na peça cirúrgica (ex-vivo). Conclusão A comparação entre os métodos mostrou acurácia praticamente similar. As vantagens do gamaprobe foram a de não ser invasivo, ser de baixo custo e também ser relevante para mostrar a redução da atividade radioativa no local da exérese. .

Radioguided occult lesion localization versus wire-guided localization for non-palpable breast lesions: randomized controlled trial

AIM: This prospective randomized clinical study was conducted to compare radioguided occult lesion localization (ROLL) with wire-guided localization to evaluate optimum localization techniques for non-palpable breast lesions. METHODS: A total of 108 patients who were undergoing an excisional biopsy for non-palpable breast lesions requiring pathologic diagnosis were randomly assigned to the ROLL group (n = 56) and wire-guided localization group (n = 52). In the study, patients' characteristics, radiological abnormalities, radiological technique of localization, localization time, operation time, weight of the excised specimen, clearance margins, pathological diagnosis and perioperative complications were assessed. RESULTS: There were no differences between the two groups in terms of age, radiological abnormalities and localization technique (p = non-significant for all). ROLL techniques resulted in 100 percent retrieval of the lesions; for the wire-guided localization technique, 98 percent. Both localization time and operation time were significantly reduced with the ROLL technique (p = significant for all). The weight of the specimen was significantly lower in the ROLL group than in the wire-guided localization group (p = significant). The overall complication rate and pathological diagnosis were similar for both groups (p = non-significant for all). Clear margins were achieved in 91 percent of ROLL patients and in 53 percent of wire-guided localization patients, and the difference was significant. CONCLUSIONS: The present study indicated that the ROLL technique is as effective as wire-guided localization for the excision of non-palpable breast lesions. In addition, ROLL improved the outcomes by reducing localization and operation time, preventing healthy tissue excision and achieving clearer margins.

New applications of radioguided surgery in oncology

OBJECTIVE: To report oncological cases (excluding those related to breast cancer) for which radioguided surgery has been used in combination with the Radioguided Occult Lesion Localization technique. INTRODUCTION: Radioguided surgery enables a surgeon to identify lesions or tissues that have been preoperatively marked with radioactive substances. The Radioguided Occult Lesion Localization technique has been widely used to identify the sentinel lymph node and occult lesions in patients with breast cancer. However, few studies have reported the use of this technique for non-breast cancer pathologies. METHODOLOGY: In all cases, injection of Technecium-99m sulfur colloid was performed, directly inside or near by the suspicious lesion, guided by ultrasound or computed tomography, up to 36 hours prior to the surgical procedure. Intraoperative lesion detection was carried out using a gamma-probe. RESULTS: We report five oncology cases in which preoperative markings of the lesions were carried out using the Radioguided Occult Lesion Localization technique. The patients presented with the following: recurrence of renal cell carcinoma, cervical recurrence of papillary carcinoma of the thyroid, recurrence of retroperitoneal sarcoma, lesions of the popliteal fossa, and recurrence of rhabdomyosarcoma of a thigh. In each case, the lesions that were marked preoperatively were ultimately successfully excised. CONCLUSIONS: Radioguided surgery has proven to be a safe and effective alternative for the management of oncology patients. The Radioguided Occult Lesion Localization technique can be useful in selected cases where suspect lesions may be difficult to identify intraoperatively, due to their dimensions or anatomical location. The procedure allows for more conservative excisions and reduces the surgery-related morbidity.

Abordagem simultânea das lesões não palpáveis da mama e do linfonodo sentinela (SNOLL) / Simultaneous management of non-palpable breast lesion and sentinel lymph node (SNOLL)

As técnicas conjuntas da mastologia com auxílio da medicina nuclear representam um importante papel na atualidade. A investigação das lesões não palpáveis da mama por meio das cirurgias radioguiadas (ROLL), e a possibilidade da cirurgia conservadora da axila, por meio da análise do linfonodo sentinela (LS), são avanços tecnológicos disponíveis e cada vez mais utilizados na prática clínica. A utilização dessas duas técnicas conjugadas (SNOLL) procura associar as facilidades de ROLL com os benefícios do linfonodo sentinela, uma vez que o amplo uso dos métodos invasivos para diagnóstico do câncer de mama, tais como PAAF, core biopsy e mamotomia, permite o planejamento cirúrgico definitivo e simultâneo do tumor e da axila.

The multidiciplinary approach plays an important role in the evaluation and treatment of breast cancer. It included nuclear medicine in the last years.The radioguided ocult localization (ROLL) and the conservative surgery of the axilla (sentinel lymph node) are pratice of choice for managemente of many patients with breast cancer. The simultaneous use of both procedures (SNOLL) associates the facilities of the radioguided localization of the breast lesion and sentinel lymph node at the same surgery; it shows some benefits once the widespread use of interventional image techniques provide histologic diagnoses and makes possible the definitive surgical management of malignant lesions of the breast.