SPECT-CT Imaging with [99mTc]PSMA-T4 in patients with Recurrent Prostate Cancer.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein with a large extracellular domain with overexpression of the prostatic tumour cells. Several small molecules of PSMA ligands of inhibitors binding to the active site of PSMA were developed. [99mTc]Tc-PSMA-T4 is a new radiopharmaceutical (Polatom) for imaging loco-regional metastases and/or local relapse in patients with prostate cancer. The purpose of this work was to evaluate the clinical application of SPECT-CT imaging with [99mTc]Tc-PSMA-T4 in patients with recurrent prostate cancer. MATERIAL AND METHODS: Thirty-six patients with prostate cancer, aged 60-80 years with biochemical relapse of PSA (ranged from 0.1 to 73 ng/mL) were included. Three patients were studied after tru-cut biopsy, hormonal and cytoreductive radiotherapy and 33 patients out of 36 - after radical treatment (total prostatectomy or definitive radiotherapy of the tumour). All of them underwent whole-body imaging examinations with subsequent target SPECT-CT studies of the pelvis, abdomen and/or chest, 1-3 hrs post i.v. administration of [99mTc]Tc-PSMA-T4. The average activity dose was 6.3 MBq/kg in a man of 70 kg. A Dual-head SPECT-CT gamma camera with a low dose CT scan (Symbia T2, Siemens) was used. The images were interpreted based on all other clinical and radiological data. Follow-up could be conducted in 11/36 patients during that period. RESULTS: Normal biodistribution of the radiopharmaceutical with high activity background was observed in the liver, spleen, kidneys, lacrimal and salivary glands, bowels and urinary bladder. Positive imaging for local relapse in the prostate bad was imaged in 21 patients, lymph node metastases - in 16 cases, bone lesions - in 10 cases, pulmonary metastases - in 2 cases, hepatic lesions were visualised in one of them and in another - adrenal suprarenal metastasis with intensive tracer uptake significant for overexpression of PSMA. There was a suspicion for local recurrences in 4 patients with negative MRT studies who were followed up. In 3 cases, previously treated bone metastases were partially negative without tracer uptake, only some progressive bone lesions were positive. Five patients were with negative results. Sensitivity was 84.37% (27/32), specificity - 100% (4/4) and accuracy - 86.11% (31/36). CONCLUSIONS: In conclusion SPECT-CT imaging with [99mTc]Tc-PSMA-T4 could be applied in patients with prostate cancer for the diagnosis of recurrent disease to determine personalized treatment for each patient. Specific uptake of this tracer, depicted by SPECT-CT images has clinical importance of identifying and assessing PSMA expression before consideration of Radio Ligand Therapy (RLT) with [¹77Lu]Lu-PSMA. SPECT-CT imaging with [99mTc]PSMA is promising and reliable nuclear medicine approach to monitoring therapeutic effect after treatment and for restaging of the disease.

Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

Ipsilateral in-breast tumor recurrence after breast conserving therapy: true recurrence versus new primary tumor.

PURPOSE: To classify ipsilateral in-breast cancer recurrences (IBCR) in patients treated with conservative surgery and radiation therapy, either as new primary tumor (NP) or true recurrence (TR) and to assess the prognostic and therapeutic importance of this classification. METHODS: The records of 107 patients treated for local tu- mor recurrence after breast-conserving therapy (BCT) at the National Cancer Center, Sofia, between March 1999 and May 2011 were retrospectively analysed. The patients'primary tumors were up to 2 cm in size. For their primary tumors all patients underwent quadrantectomy, axillary lymph node dissection and postoperative radiotherapy (RT) up to 50 Gy. In cases with nodal metastasis additional RT has been used. Adjuvant chemotherapy and hormonotherapy have been used according to the clinical indications and depending of the patient's condition. Every attempt was made to define a tumor as a TR or NP, based on the changes in location and histology. (99m)Tc-MIBI SPECT-CT was used to localize the site of recurrence. RESULTS: Forty-four (41.1%) of the relapses were TR and 63 (58.9%) NPs. Out of 63 relapses defined as NPs, 54 (85.7%) changed the location and 49 (68.3%) had a different histology. The age of patients with TR and with NP did not differ significantly at the time of diagnosis of the primary tumor (TR 48.8±10.45 years vs NP 50.8±10.56; p<0.330), but those who developed TR were significantly younger than those with NP at the time of recurrence (TR 53 years, 66±11.1 vs NP 58.15+10.6; p<0.05). Recurrences defined as NPs, developed after a significantly longer period of time in comparison to the TRs (7.4±2.6 years vs 4.8±2.2 years; p<0.0001). Five-year overall survival of patients with TR was significantly lower compared to patients with NP (31.8% vs 96.7% p=0.0001). CONCLUSIONS: Recurrences developing after BCT represent different clinical events, having different origin, prognosis and, therefore, requiring different type of treatment. It seems that a significant part of the recurrences that develop in the residual parenchyma, following BCT, are new carcinomas.

Results of a Prospective Multicenter International Atomic Energy Agency Sentinel Node Trial on the Value of SPECT/CT Over Planar Imaging in Various Malignancies.

UNLABELLED: We aimed to assess the additional value of SPECT/CT over planar lymphoscintigraphy (PI) in sentinel node (SN) detection in malignancies with different lymphatic drainage such as breast cancer, melanoma, and pelvic tumors. METHODS: From 2010 to 2013, 1,508 patients were recruited in a multicenter study: 1,182 breast cancer, 262 melanoma, and 64 pelvic malignancies (prostate, cervix, penis, vulva). PI was followed by SPECT/CT 1-3 h after injection of (99m)Tc-colloid particles. Surgery was performed the same or next day. RESULTS: Significantly more SNs were detected by SPECT/CT for breast cancer (2,165 vs. 1,892), melanoma (602 vs. 532), and pelvic cancer (195 vs. 138), all P < 0.001. The drainage basin mismatch between PI and SPECT/CT was 16.5% for breast cancer, 11.1% for melanoma, and 51.6% for pelvic cancers. Surgical adjustment was 17% for breast cancer, 37% for melanoma, and 65.6% for pelvic cancer. CONCLUSION: SPECT/CT detected more SNs and changed the drainage territory, leading to surgical adjustments in a considerable number of patients in all malignancies studied but especially in the pelvic cancer group because of this group's deep lymphatic drainage. We recommend SPECT/CT in all breast cancer patients with no SN visualized on PI, all patients with melanoma of the head and neck or trunk, all patients with pelvic malignancies, and those breast cancer and melanoma patients with unexpected drainage on PI.

SPECT-CT in Radiotherapy Planning, with Main Reference to Patients with Breast Cancer.

The aim of modern intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) is to define the target areas including the smallest non-invaded margins, thus reducing the radiation dose to radiosensitive organs. To reach this goal, these methods require a more precise target delineation by imaging to better define the viable part of the tumor. Image-guided selection and demarcation of Gross Tumor Volume (GTV), Clinical Target Volume (CTV) and Organs at Risk (OAR) are the main steps to reach a satisfactory radiation treatment plan. Hybrid machines, such as PET-CT, SPECT-CT and, more recently, PET-MRI, may significantly increase diagnostic accuracy improving either sensitivity and specificity achievable alone by the single constituents of the hybrid tools. While the implementation contribution of PET-CT in radiotherapy, with respect to CT stand alone, has been extensively and successfully investigated, few papers have been at present written on the possible role of SPECT-CT for the same purpose. With an identical contribution to CT, SPECT may give similar information with respect to PET, when suitable radiopharmaceuticals are available. In particular, SPECT may provide additional information to CT, better defining the viable tumor mass; as a consequence, a more effective delineation of the GTV, saving the maximum normal tissue as possible, may be allowed. In this paper, we review some of the most important applications of SPECT-CT in oncology, as a premise to its possible utilization in tumor target definition in radiotherapy. In particular, we discuss sentinel lymph node (SLN) detection, tumor imaging with cationic lipophilic radiotracers, as (99m)Tc-methoxyisobutylisonitrile (MIBI) and (99m)Tc-tetrofosmin (TF) in breast cancer, thymoma, and lung cancer, (99m)Tcmethylene diphosphonate (MDP) for bone scan, (131)Iodine and (123)Iodine in differentiated thyroid cancer (DTC), as useful methods to optimize GTV and CTV definition. A reflection on the possible role in radiotherapy of other radiotracers labeled with gamma emitters, such as In-111 pentreotide has also been included.

Role of SPECT-CT in radiotherapy.

PURPOSE: The role of fusion imaging methods SPECT-CT and PET-CT is currently being investigated in radiotherapy (RT) treatment planning. SPECT and PET provide extra information for gross tumor volume (GTV) delineation. The purpose of this study was to evaluate the role of SPECT-CT in RT. METHODS: SPECT-CT studies were performed in 55 patients with (99m)Tc-MIBI/Tetrofosmin (TF), with 99mTc-Nanoco, with 99mTc-MDP and with 185 MBq (131)I scan. All studies were performed with SPECT-CT camera, using low dose CT (130KeV, 30 mA, 3-5 mm step). Corresponding slices on SPECT-CT were compared to the diagnostic CT projections from the simulator. Diagnostic CT scans were performed using 3-5 mm slices both to aid volume definition and to create high quality digitally reconstructed radiographs (DRRs) to aid verification. The volumetric CT data were sent to the treatment planning system. RESULTS: Application of SPECT-CT with (99m)Tc-MIBI/TF allowed to diagnose residual malignant mass or a recurrent tumor after combined (surgery and chemotherapy/ hormonotherapy/ therapy in studied patients with breast cancer, thymomas and lung cancer. SPECT-CT (99m)Tc-MIBI/ TF contributed to the definition of clinical target volume (CTV). SPECT-CT imaging of sentinel lymph nodes (SLNs) in medially located breast cancer was important for correct topography of intercostal space in cases with parasternal drainage. Irradiation of this subgroup of patients in conjunction with the chest wall and the supraclavicular region should be considered electively for each patient. The combined application of baseline whole body bone scintigraphy, followed by SPECT-CT fusion gave the possibility for correct radiotherapy planning of the GTV in tumor-induced bone disease. SPECT-CT is useful for diagnosis of recently discovered non-responsive to (131)I treatment patients with differentiated thyroid cancer. SPECT-CT data are important to avoid prescribed (131)I therapy and to define CTV for external beam RT (EBRT). CONCLUSION: SPECT-CT images could be applicable in RT planning to precisely delinate tumor volume.

Radiation-induced breast cancer in women with Hodgkin's disease.

AIM AND BACKGROUND: The aim of this study is to analyze the main clinical and pathologic characteristics of radiation-induced breast carcinomas (BC) following treatment for Hodgkin's disease (HD) and to identify the risk factors for their induction. To create a mathematical model for the prediction of expected age at which a BC might develop based on the age at treatment for HD. MATERIALS AND METHODS: Thirty-nine cases of women with BC that developed after treatment for HD in puberty or adolescence were analyzed retrospectively. The median age at initiation of treatment for HD was 12.9 years (9-21). The median age at diagnosis of the second malignancy - breast carcinoma was 32.4 years (22.9-39). RESULTS: THE DISTRIBUTION OF PATIENTS ACCORDING TO THE CLINICAL T STAGE OF BREAST CANCER WAS AS FOLLOWS: 11 patients with T1 stage BC (28%), 22 with T2 stage (56%) and 6 with stage T3 (16%). Prevalent were tumors localized in the lateral breast quadrants. The observed 5 year survival was 95%. CONCLUSION: The risk of solid tumors, especially breast cancer, is high among women with HD disease who were treated with radiotherapy in their childhood. In this article, we propose a specific mathematical age formula which could be used as predictive equation when the age of the treatment for HD is in the range between 9 and 21 years. Systematic screening for breast cancer in these patients would be significantly important for their health and could improve their survival.

Primary angiosarcoma of the breast complicated by the syndrome of disseminated intravascular coagulation (DIC): Case report and literature review.

Primary angiosarcoma of the breast (PAB) accounts for 0.04% of all breast malignant tumors. It affects young women usually at third or fourth decades of life. PAB clinically manifests as a painless, movable mass with sharp limits. A bluish red discoloration of the overlying skin is often observed. Enlargement of axillary lymph nodes generally does not occur. Angiosarcoma of the breast has a very poor prognosis due to the tendency to metastasize haematogenously and high frequency of local recurrence. Mastectomy and chemotherapy are preferable treatment choices. This paper presents a case of primary angiosarcoma of the breast with a syndrome of disseminated intravascular coagulation (DIC).