Detection rate, pattern of relapse and influence on therapeutic decision of PSMA PET/CT in patients affected by biochemical recurrence after radical prostatectomy, a retrospective case series.

AIMS: 68Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported. RESULTS: 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003). CONCLUSIONS: PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging.

PET/TC 11C-colina detecta múltiples pequeñas metástasis peritoneales en un paciente con cáncer de próstata / 11C-Choline PET/CT detects multiple small peritoneal metastasis in a prostate cancer patient

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Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

AIM: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. MATERIALS AND METHODS: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). RESULTS: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). CONCLUSION: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

18F-FDG PET/CT scan confirmed by pathology findings in a singular case of squamous cell carcinoma of the epiglottis.

BACKGROUND: Only about 1% of all head and neck lateral or paramedian cancers described in the scientific literature shows, in staging, contralateral cervical adenopathy without ipsilateral pathological involvement of lymph nodes. CASE PRESENTATION: This case is one of them, in which 18F-FDG PET/CT scan is confirmed by pathology findings, and has correctly identified all metastatic disease foci. CONCLUSIONS: To date, PET/CT is not recommended in head and neck cancer staging. However, the use of PET/CT in head and neck cancer staging can define possible metastatic disease foci, clarify c.e. CT suspicious findings and, in some cases, change the TNM stage, with a strong prognostic and therapeutic impact.

Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]tracers, [11C]/[18F]-HTP).

Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate.

Imaging biomarkers in prostate cancer: role of PET/CT and MRI.

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed.

Imaging in resectable colorectal liver metastasis patients with or without preoperative chemotherapy: results of the PROMETEO-01 study.

BACKGROUND: The aim of the PROMETEO-01 Study was to define the diagnostic accuracy of imaging techniques in colorectal cancer liver metastasis (CRCLM) patients. METHODS: Patients referred to Bologna S. Orsola-Malpighi Hospital performed a computed-tomography scan (CT), magnetic resonance (MR), 18F-FDG-PET/CTscan (PET/CT) and liver contrast-enhanced-ultrasound (CEUS); CEUS was also performed intraoperatively (i-CEUS). Every pathological lesion was compared with imaging data. RESULTS: From December 2007 to August 2010, 84 patients were enrolled. A total of 51 (60.71%) resected patients were eligible for analysis. In the lesion-by-lesion analysis 175 resected lesions were evaluated: 67(38.3%) belonged to upfront resected patients (group-A) and 108 (61.7%) to chemotherapy-pretreated patients (group-B). In all patients the sensitivity of MR proved better than CT (91% vs 82%; P=0.002), CEUS (91 vs 81%; P=0.008) and PET/CT (91% vs 60%; P=0.000), whereas PET/CT showed the lowest sensitivity. In group-A the sensitivity of i-CEUS, MR, CT, CEUS and PET/CT was 98%, 94%, 91%, 84% and 78%, respectively. In group-B the i-CEUS proved equivalent in sensitivity to MR (95% and 90%, respectively, P=0.227) and both were significantly more sensitive than other procedures. The CT sensitivity in group-B was lower than in group-A (77% vs 91%, P=0.024). CONCLUSIONS: A thoraco-abdominal CT provides an adequate baseline evaluation and guides judgment as to the resectability of CRCLM patients. In the subset of candidates for induction chemotherapy to increase the chance of liver resection, the most rational approach is to add MR for the staging and restaging of CRCLM.

Estudio de diagnóstico por imagen de recidiva tras el tratamiento radical de cáncer de próstata: ¿cómo distinguir entre la enfermedad local y la enfermedad a distancia? Punto de vista del urólogo / Diagnostic imaging work-up for disease relapse after radical treatment for prostate cancer: How to differentiate local from systemic disease? The urologist point of view

Alrededor del 40% de los pacientes que se someten a tratamiento radical de cáncer localizado de próstata (CaP) desarrollan una recidiva bioquímica (RB) a lo largo de su vida, aunque únicamente el 10–20% de ellos manifestará recidivas clínicamente detectables. El lecho prostático, los ganglios pélvicos o retroperitoneales y los huesos (principalmente la columna) son los emplazamientos en los que debemos centrar nuestra atención durante la fase inicial de la recidiva del cáncer de próstata. El tiempo transcurrido hasta la recidiva del PSA, la cinética del PSA, la puntuación patológica de Gleason y el estadio patológico son los principales factores relacionados con la probabilidad de una recidiva local frente a una recidiva a distancia. Antes de realizar un estudio diagnóstico amplio en pacientes con RB, es imperativo comprender si existe o no una consecuencia terapéutica para el paciente. Las técnicas actuales de imagen tienen algún potencial, aunque todavía se siguen encontrando muchos límites en el diagnóstico de la recidiva de la enfermedad. La ecografía transrectal (TRUS) y la resonancia magnética multiparamétrica son poco precisas para la detección de la recidiva. Hoy en día, el PET/TAC de Colina puede visualizar el emplazamiento de la recurrencia de forma más temprana, con una mejor precisión que la imagen convencional, en un único paso e incluso en presencia de un bajo nivel de PSA. En los últimos años, se ha propuesto el nuevo radiotrazador 18F-FACBC como una posible alternativa radio-farmacéutica para la detección de la recidiva del CaP. Desde un punto de vista clínico, los primeros estudios clínicos mostraron unos resultados muy prometedores y reproducibles, con una mejora de la sensibilidad de alrededor de un 20–25% con respecto al PET/TAC de Colina, lo que convierte al FACBC en el posible radiotrazador del futuro para el CaP. En conclusión, se han logrado recientemente muchas mejoras en cuanto a técnicas de imagen para la re-estadificación del CaP, principalmente en Medicina Nuclear y RM, aunque persisten los resultados negativos en muchos casos. La baja sensibilidad, los costes, la disponibilidad de las tecnologías y la confirmación de los resultados siguen siendo las principales limitaciones en muchos casos(AU)

About 40% of all patients undergoing radical treatment for localized prostate cancer (PCa) develop biochemical relapse (BCR) during lifetime but only 10–20% of them will show clinically detectable recurrences. Prostatic bed, pelvic or retroperitoneal lymph nodes (LN) and bones (especially the spine) are the sites where we must focus our attention in the early phase of PSA relapse. Time to PSA relapse, PSA kinetics, pathological Gleason score and pathological stage are the main factors related to the likelihood of local vs. distant relapse. Before an extensive diagnostic work-up in patients with BCR, is mandatory to understand if there is a therapeutic consequence or not for the patient. Current imaging techniques have some potential but many limits are yet encountered in the diagnosis of disease relapse. Transrectal ultrasound (TRUS) and Multiparametric Magnetic Resonance Imaging (MRI) have low accuracy in the detection of the recurrence. Today, Choline PET/CT may visualize the site of recurrence earlier, with better accuracy than conventional imaging, in a single step and even in the presence of low PSA level. In recent years, the new radiotracer 18F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. From a clinical point of view, first clinical studies showed very promising and reproducible results with an improvement in sensitivity is about 20–25% with respect to Choline PET/CT, rendering the FACBC the possible radiotracer of the future for PCa. In conclusion, many improvements have been recently achieved in imaging techniques for PCa restaging, essentially in Nuclear Medicine and MRI, but negative results remain in many cases. Low sensitivity, costs, availability of technologies and confirmation of the results remain the major limitations in most cases(AU)

Diagnostic imaging work-up for disease relapse after radical treatment for prostate cancer: how to differentiate local from systemic disease? The urologist point of view.

About 40% of all patients undergoing radical treatment for localized prostate cancer (PCa) develop biochemical relapse (BCR) during lifetime but only 10-20% of them will show clinically detectable recurrences. Prostatic bed, pelvic or retroperitoneal lymph nodes (LN) and bones (especially the spine) are the sites where we must focus our attention in the early phase of PSA relapse. Time to PSA relapse, PSA kinetics, pathological Gleason score and pathological stage are the main factors related to the likelihood of local vs. distant relapse. Before an extensive diagnostic work-up in patients with BCR, is mandatory to understand if there is a therapeutic consequence or not for the patient. Current imaging techniques have some potential but many limits are yet encountered in the diagnosis of disease relapse. Transrectal ultrasound (TRUS) and Multiparametric Magnetic Resonance Imaging (MRI) have low accuracy in the detection of the recurrence. Today, Choline PET/CT may visualize the site of recurrence earlier, with better accuracy than conventional imaging, in a single step and even in the presence of low PSA level. In recent years, the new radiotracer (18)F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. From a clinical point of view, first clinical studies showed very promising and reproducible results with an improvement in sensitivity is about 20-25% with respect to Choline PET/CT, rendering the FACBC the possible radiotracer of the future for PCa. In conclusion, many improvements have been recently achieved in imaging techniques for PCa restaging, essentially in Nuclear Medicine and MRI, but negative results remain in many cases. Low sensitivity, costs, availability of technologies and confirmation of the results remain the major limitations in most cases.

The dilemma of localizing disease relapse after radical treatment for prostate cancer: which is the value of the actual imaging techniques?

Only few patients with PSA relapse after radical treatment will show clinically detectable disease. Although the natural history of recurrent prostate cancer is often one of the slowly progressing diseases, in some men it can be rapid and may need a salvage treatment. In general, time to PSA relapse, PSA velocity and PSA doubling time are useful in patient assesment. In patients with PCa disease relapse after primary therapy, salvage treatment for a local recurrence should only be offered to patients with little risk of already having metastases. In these patients a systemic imaging negative for metastases is mandatory, a positive biopsy is not always necessary before radiotherapy, but is mandatory before salvage prostatectomy. In patients with a high risk of distant metastases and suitable for systemic salvage therapy, a positive lesion must be obviously visualized with one of the currently available imaging techniques. Transrectal ultrasound has low accuracy in the detection of the recurrence. Multiparametric Magnetic Resonance Imaging may have a role in the early phase of PSA relapse. Conventional imaging, such as bone scan and CT, are not suggested in the initial phase of BCR. Today, it has been reported that PET/CT allows changing the therapeutic strategy (from palliative to curative treatment and vice-versa) in about 20% of cases. In recent years, the new radiotracer 18F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. The aim of the present paper is to evaluate the management of patients with BCR after radical treatment of PCa from the urologist point of view.

PET/CT in prostate cancer: non-choline radiopharmaceuticals.

In this brief review, the major potential clinical applications of 18F-FDG, 11C-acetate, 18F-FDHT, 18F-FLT, 18F-FMAU, and anti-18F-FACBC in the imaging evaluation of men with prostate cancer are discussed. 18F-FDG has a limited role in primary diagnosis and staging but it may be able to reflect tumour aggressiveness, detect sites of recurrence in some men with high serum PSA after biochemical failure and assess response to chemo- and hormonal treatment in metastatic disease. 11C-acetate has been investigated for intra-prostatic primary tumour detection and staging as well as for re-staging in case of biochemical relapse with results that are overall similar to those with 18F- and 11C-labeled choline. 18F-FDHT targets the androgen receptor and may be particularly useful in the assessment of the pharmacodynamics of the androgen signalling pathway. PET in conjunction with 18F-FLT or 18F-FMAU that track the thymidine salvage pathway of DNA synthesis has also been investigated for imaging cellular proliferation in prostate cancer. Initial experience with the radiolabeled synthetic amino acid, anti-18F-FACBC, which displays slow urinary excretion has been encouraging but further studies will be needed to decipher its exact role in the imaging management of men with prostate cancer.

Prospective study on the FDG-PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer.

BACKGROUND: 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was carried out before and after neoadjuvant chemoradiotherapy (NCRT) followed by radical surgery for locally advanced rectal cancer (LARC). The aim of this study was to define its predictive and prognostic values. PATIENTS AND METHODS: Patients with cT3-T4 N-/+ carcinoma of medium/low rectum received daily 5-fluorouracil-based chemotherapy infusion and radiation therapy on 6-week period followed by surgery 7-8 weeks later. Tumour metabolic activity, expressed as maximum standardised uptake value (SUV-1 = at baseline and SUV-2 = pre-surgery), was calculated in the most active tumour site. Predictive and prognostic values of SUV-1, SUV-2 and Δ-SUV (percentage change of SUV-1 - SUV-2) were analysed towards pathological response (pR) in the surgical specimen and disease recurrence, respectively. RESULTS: Eighty consecutive patients entered the study. SUV-1, SUV-2 and Δ-SUV appeared singly correlated with pR, but not one of them resulted an independent predictive factor at multivariate analysis. After a median follow-up of 44 months, 13 patients (16.2%) presented local and/or distant recurrence. SUV-2 ≤5 was associated with lower incidence of disease recurrence and resulted prognostic factor at multivariate analysis. CONCLUSIONS: Dual-time FDG-PET/CT in patients with LARC treated with NCRT and radical surgery supplies limited predictive information. However, an optimal metabolic response appears associated with a favourable patient outcome.

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

FDG PET and 90Y ibritumomab tiuxetan in patients with follicular lymphoma.

AIM: Despite its established utility in non-Hodgkin's lymphoma, not much is reported on FDG positron emission tomography (PET) with respect to radioimmunotherapy (RIT). In this paper we investigate its value in patients affected by follicular lymphoma (FL) before and after treatment with [90Y]Ibritumomab Tiuxetan (Zevalin(R)). METHODS: We evaluated 38 relapsed or refractory FL patients. All had a PET scan performed before and 3 months after radioimmunotherapy. Final assessment was done 9 months post-RIT, including clinical evaluation, other imaging techniques and/or biopsy, when necessary. RESULTS: At the first PET scan 20 patients out of 38 had a limited disease (nodal involvement on one side of the diaphragm: 7 above and 13 below), 11 patients had nodal findings on both sides of the diaphragm and the remaining 7 patients had both nodal and extra-nodal findings. At three months post-RIT, 21 patients (55%) were in complete remission, 13 patients (34%) had a partial response (PR) and four patients (11%) had a progression disease (PD). The corresponding rates at final assessment were all consistent with the 3-month evaluation: 55% CR, 13% PR and 32% PD. FDG PET scan revealed maximal predictive values. When comparing the disease extent at relapse and the response to treatment, we could testify a higher rate of CR (75%) in patients with limited disease, while in patients with diffused nodal and/or extra-nodal findings, it was more frequent a PR or PD (66%). CONCLUSION: Our data are concordant with the expected results on RIT, and FDG PET is confirmed to be useful in assessing treatment response. Potential correlation can also be picked out between the disease extent at relapse and the CR rate, with reasonable PET predictivity for the final outcome.

MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis: experience on seven patients.

BACKGROUND: Adult Langerhans cell histiocytosis (LCH) is a rare disease. The combination of vinblastine and prednisone, given in a 6-month course, is the standard of care but prospective randomized trials are lacking. PATIENTS AND METHODS: We report our monocentric experience in the treatment of seven adult patients with multisystem (MS) LCH (n = 3) or single-system multifocal (SS-m) LCH (n = 4) with the short-course intensive chemotherapy regimen methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomicin (MACOP-B). RESULTS: The overall response rate was 100% [five complete response (CR), two partial response (PR)]. After a median follow-up of 6.5 years, four patients are in first continuous CR and three patients relapsed after 5, 8 and 62 months, respectively. Four patients were evaluated with positron emission tomography (PET) scan: all three PET-negative patients at the end of treatment had a long-lasting response with only one patient relapsing after 5 years. PET scan detected additional bone lesions at diagnosis in two of four patients, changing the treatment program in one of them. CONCLUSIONS: MACOP-B regimen seems to be very active in the treatment of adult MS or SS-m LCH, with long-lasting responses in five of seven patients. PET scan merits further evaluation in the initial staging and in the evaluation of the response to chemotherapy.

Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model.

The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

Positron-emission tomography in imaging and staging prostate cancer.

With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment.