Jean-Luc Moretti

18F-FDG PET/CT bone/bone marrow findings in Hodgkin’s lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging

PurposeAccurate staging of Hodgkin’s lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. 18F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant 18F-FDG PET/CT.MethodsData from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and 18F-FDG PET/CT. Results of BMB were not available at the time of 18F-FDG PET/CT imaging.ResultsSeven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on 18F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on 18F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy 18F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient.Conclusion18F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging.

Effect of 18F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

PURPOSE To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

18F-FDG PET/CT Imaging for an Early Assessment of Response to Sunitinib in Metastatic Renal Carcinoma: Preliminary Study

PURPOSE Sunitinib is a new standard for the treatment of metastatic renal-cell carcinoma (RCC). We evaluated the accuracy of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in assessing early response to this antiangiogenic drug, which cannot be obtained with conventional CT. PROCEDURES Patients had an FDG-PET/CT at baseline and another one for follow-up at the end of the first cycle (at day 42). For each examination, all lesions were registered and the maximum standardized uptake value (SUV(max)) was measured. The metabolic response on PET at day 42 was assessed, using European Organization for Research and Treatment of Cancer criteria. Morphologic response on CT at day 84 (after two cycles), using Response Evaluation Criteria in Solid Tumors criteria, was used as the reference standard. The long-term outcome was assessed by the progression-free survival. RESULTS Twelve (12) patients who completed at least two cycles of sunitinib were assessed. The SUV(max) for the lesions with the highest uptake ranged between 2.9 and 11.8 for the 12 patients (mean = 6.3). Early PET/CT findings, after one cycle of sunitinib, were consistent with later CT results in 9 patients of 11 assessable patients: 1 patient progressed on PET and CT, 7 patients had stable disease, and 1 had a partial response. The other 2 patients had a metabolic partial response on PET and stable disease on CT. However, 1 patient achieved a partial response later in follow-up, suggesting that metabolic early changes are an indication of sunitinib activity. CONCLUSION FDG-PET/CT seems to be an interesting tool for the early evaluation of response to sunitinib in metastatic RCC. Larger studies are needed to confirm these preliminary results and establish a prognostic value for PET/CT.

Early monitoring of response to neoadjuvant chemotherapy in breast cancer with 18F-FDG PET/CT: defining a clinical aim

In Europe, in 2008, it was estimated that 421,000 new cases of breast cancer were diagnosed; 129,000 women died from breast cancer in the same year [1]. Neoadjuvant chemotherapy (NAC), initially used only for locally advanced breast cancer, is now commonly used in patients with operable but large breast cancer. This strategy allows patients to undergo breast-conserving surgery (BCS) and gives information on the efficacy of chemotherapy [2]. Long-term outcomes are significantly correlated with pathological tumour response rates [3]. In the present paper we here focus on what could be the role of an early evaluation with F-FDG PET/CT of the response to NAC in patients with operable breast cancer.

Primary breast cancer imaging with technetium-99m sestamibi and its relation with P-glycoprotein overexpression

The aim of this preliminary study was to evaluate retrospectively sestamibi scintigraphy in relation to the presence of the 170-kDa P-glycoprotein (Pgp), which represents an expression of multidrug resistance in patients with primary breast cancer. Fifteen women (age range 37–76 years) were referred for technetium-99m sestamibi scintigraphy because of suspicious breast lesions detected by mammography and ultrasonography, and subsequently assessed by fine-needle aspiration. Scintigraphy was performed 30 min following the injection of 500 MBq99mTc-sestamibi. Three planar anterior and oblique images were obtained with the patient in the supine position. Excised tumours were assessed for cytosolic CA 15.3, oestrogen (OR) and progesterone (PR) receptors and c-erb B2neu oncogene. Pathology revealed that only 13 of the 15 patients had malignant tumours. The two benign tumours were sestamibi-negative and Pgp-positive. Sestamibi scintigraphy was positive in 10 of the 13 malignant lesions (including nine of ten infiltrating ductal carcinomas). Two of the three lesions with false-negative scintigraphy were Pgp-negative; in one of these cases histology revealed an invasive lobular carcinoma and in the other, mucinous adenocarcinoma. The third false-negative lesion was a Pgp-positive infiltrating ductal carcinoma which was c-erb B2neu-negative but CA 15.3-, OR- and PR-positive. This preliminary study confirms that the resistance to chemotherapy which may occur in patients with primary breast cancer can be a cause of negative sestamibi scintigraphy.

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of123I-isopropyl-iodoam-phetamine (123I-IMP) and99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with123I-IMP and99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal99mTc-HMPAO SPECT and abnormal123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on99mTc-HMPAO in areas corresponding to defects on the123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with99mTc-HMPAO and was absent for both123I-IMP and99mTc-HMPAO in 3. We suggest that SPECT with99mTc-HMPAO could show transient hyperemia not demonstrated by123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with99mTc-HMPAO than with123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.

Quercetin, Siamois 1 and siamois 2 induce apoptosis in human breast cancer MDA-MB-435 cells xenograft in vivo

We sought to investigate the apoptosis-inducing activities of quercetin, Siamois 1, and Siamois 2 against invasive estrogen-receptor negative MDA-MB 435 cells xenografted in athymic nude mice. This study clearly demonstrated that these compounds exhibited apoptosis-inducing activities in cell culture system. Quercetin (20 μg/mL), Siamois 1 (100 μg/mL), and Siamois 2 (200 μg/mL) can induce apoptotic cell death by 40± 5%, 44 ± 14 %, and 31 ± 13 %, respectively. Two-fold of IC50 of these compounds were clearly found to induce apoptosis in breast tumor tissue which can be determined by 99mTc-annexin V scintigraphy and histological staining. This is the first report that the apoptosis-inducing effects of quercetin, Siamois 1, and Siamois 2 on the MDA-MB 435 cell in vitro were effectively extrapolated to the in vivo situation. These compounds might be considered as a simple dietary supplement and with further clinical investigation for their use as a nutrition-based intervention in breast cancer treatment.

Sequential functional imaging with technetium-99m hexakis-2-methoxyisobutylisonitrile and indium-111 octreotide: can we predict the response to chemotherapy in small cell lung cancer?

A case of small cell lung carcinoma (SCLC) demonstrating uptake on functional indium-111 octreotide scintigraphy is presented. Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy clearly delineated an absence of radionuclide uptake at the tumour site. This suggested the presence of multidrug resistance-mediated P glycoprotein (Pgp) on tumour cells, which recognizes certain chemotherapeutic agents as well as MIBI as a substrate and avoids radionuclide concentration. Following three courses of chemotherapy, the patient failed to improve and eventually died. This case demonstrates the importance of functional images, which have the potential to predict the outcome in response to chemotherapy.

To use MIBI or not to use MIBI? That is the question when assessing tumour cells

Abstract99mTc-sestamibi (MIBI) is a well-known tumour imaging agent. Its retention within tumour cell mitochondria is related to perfusion and to the magnitude of the electrical gradient, reflecting cell viability. Several internal cell factors modulate this uptake; for example, multidrug resistance membrane proteins (Pgp and MRP1) and anti-apoptotic BCl-2 protein of the outer mitochondrial membrane can limit retention of MIBI. At the early stage of cell apoptosis, the electrical driving forces of MIBI uptake are impaired, and influx and accumulation are reduced. It seems clear that MIBI can be used before treatment to detect drug resistance, assess anti-apoptotic status and predict treatment efficacy. Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance.

Cortical perfusion assessment with 123I-isopropyl amphetamine (123I-IAMP) in normal pressure hydrocepha lus (NPH)

NPH can be reversible after cerebrospinal fluid (CSF) diversion. In the past no reliable criteria could be defined to predict the successful outcome of CSF shunting. Several authors demonstrated an increased cerebral blood flow after lumbar puncture in patients with NPH, indicating an underlying impairment of cerebral circulation autoregulation. 123I-AMP brain tomoscintigraphy was applied to 23 individuals with NPH before and after CSF drainage. Of these 23 patients, 10 underwent surgical shunting. The frontal and parietal hypoactive cortical pattern was present in NPH but not pathognomonic. Under stimulation of CSF pressure lowering, seven patients with improved outcome after shunting demonstrated an increase of cerebral perfusion in these areas, whereas a decrease of activity was found in three patients whose clinical status was unchanged after CSF diversion. This tomoscintigraphic test may be an interesting additional criterion for surgical admission.