Daniela Sanna

131I SPECT/CT in the Follow-up of Differentiated Thyroid Carcinoma: Incremental Value Versus Planar Imaging

Planar 131I scintigraphy is routinely used to detect radioiodine-avid metastases of differentiated thyroid carcinoma (DTC). However, the modality has limitations, such as low sensitivity and lack of anatomic landmarks. We investigated whether SPECT with integrated low-dose CT may have additional value over planar imaging in detecting residue and metastases in DTC patients. Methods: We studied 117 consecutive thyroidectomized DTC patients. On 2 different hybrid dual-head γ-cameras (55 patients on one camera and 62 on the other), 108 patients underwent 131I diagnostic imaging and SPECT/CT, and 9 underwent posttherapeutic 131I planar imaging and SPECT/CT. We assigned an incremental value to SPECT/CT when it provided better identification and interpretation of the foci of radioiodine uptake, more correct anatomic localization and characterization, and precise differentiation between tumor lesions and physiologic uptake. Results: Planar imaging showed 116 foci of uptake in 52 of 117 patients, and SPECT/CT showed 158 foci in 59 of 117 patients, confirming all foci seen on planar imaging but identifying an additional 28 occult foci in 10 of 52 patients. Fourteen occult foci were shown on SPECT/CT in 7 further patients whose planar imaging findings were negative. SPECT/CT correctly characterized 48 foci unclear on planar imaging, also defining location and extent. SPECT/CT was a determinant in classifying as neoplastic those foci for which planar imaging seemed to exclude malignancy, discriminating between residue and lymph node metastases in the neck, some of which were adjacent to salivary glands and had been missed on planar imaging. SPECT/CT also showed occult lesions in the mediastinum, abdomen, and pelvis and identified small bone metastases unsuspected on planar imaging. Globally, SPECT/CT had an incremental value over planar imaging in 67.8% of patients, modified therapeutic management in 35.6% of positive cases, and avoided unnecessary treatment in 20.3% of patients with only single benign lesions or physiologic uptake. Conclusion: 131I SPECT/CT improved planar data interpretation, showing a higher number of DTC lesions, more precisely localizing and characterizing DTC foci, and more correctly differentiating between physiologic uptake and metastases, thus permitting the most appropriate therapeutic approach to be chosen. A wider use of this method is suggested complementary to planar imaging in selected DTC patients.

The role of planar scintimammography with high-resolution dedicated breast camera in the diagnosis of primary breast cancer.

Planar scintimammography (SM) acquired with a conventional γ camera has proved a useful complementary tool to mammography (Mx) in breast cancer (BC) diagnosis, but with unsatisfactory sensitivity in small size carcinomas. In this study we assessed the role of planar SM with a high-resolution dedicated breast camera (DBC) in BC diagnosis, comparing the results with those of Mx. A consecutive series of 145 patients scheduled for biopsy for suspected BC underwent Tc-99m tetrofosmin planar SM using a newly developed DBC. Scintigraphic data were compared with Mx findings and correlated to histology. Histopathologic analysis revealed 165 lesions: 143 malignant and 22 benign. SM detected 139/143 carcinomas (overall sensitivity: 97.2%) and was true negative in 19/22 benign lesions (overall specificity: 86.4%). SM sensitivity was 91% in ≤10-mm carcinomas. SM was more accurate than Mx in 42/145 cases (29%), detecting cancer in 9 patients with Mx indeterminate for dense breasts (8/9 tumors were <10 mm), assessing additional tumor foci (all <10 mm) in 5 points with multifocal disease and correctly classifying 28 patients with inconclusive mammographic findings as affected by cancer or by benign disease. Mx was more accurate than SM in 3 patients, in each detecting 1 subcentimeter BC false negative on SM. DBC planar SM seems a highly sensitive diagnostic tool in the detection of BC, even when small in size, and in the assessment of multifocal disease. A wider employment of this procedure is thus suggested, especially in indeterminate or inconclusive mammographic findings to improve sensitivity and specificity of Mx.

Oct4 expression in in-vitro-produced sheep blastocysts and embryonic-stem-like cells.

Transcription factor Oct4 (octamer‐binding transcription factor‐4) is important in early embryonic development and differentiation. It is also required for maintenance of pluripotency of the inner cell mass, and is used as a staminality marker of embryonic stem cells. Changes in Oct4 expression during the different stages of early embryo development have been reported, and therefore we have conducted a quantitative study of Oct4 gene expression of sheep blastocysts in vitro, and of embryonic‐stem‐like cells at the undifferentiated stage and in the course of differentiation. To characterize embryonic‐stem‐like cells, alkaline phosphatase activity, stage‐specific embryonic surface antigens SSEA‐1, SSEA‐3, SSEA‐4 and three specific gene markers Nanog, Sox2 and Stat3 were assayed. cDNA produced by RT (reverse transcriptase)–PCR was synthesized and amplified by PCR; sequencing gave 98, 95 and 98% homology with the bovine sequences of Oct4, Nanog and Stat3 respectively. Using the ovine sequence of 290 bp, quantitative expression of Oct4 in the inner cell mass, trophoblast and embryonic‐stem‐like cells was performed by qRT‐PCR (quantitative real‐time PCR). Oct4 was expressed in the inner cell mass, trophoblast and embryonic‐stem‐like cells. Expression in the inner cell mass was significantly higher than in the trophoblast. This could be useful in defining the quality of embryos produced and makes it possible to use Oct4 to detect pluripotency. In addition, the different levels of Oct4 expression between undifferentiated and differentiating embryonic‐stem‐like cell cultures could be used to detect this gene as a staminality marker.

Good quality sheep embryos produced by superovulation treatment without the use of progesterone devices

Multiple ovulation and embryo transfer (MOET) is a very important tool for the genetic improvement and preservation of endangered livestock. However, the success of a MOET programme highly depends on the number of transferable embryos in response to a superovulation treatment. Thus, the aim of this study was to compare the number and quality of embryos produced during natural oestrus under porcine FSH treatment without the use of progesterone devices to more traditional protocols. Forty Sarda sheep were divided into 2 groups: without sponges (WS) (n = 20) and with sponges (S) containing 40mg FGA for 12 d (n = 20) (control group); 350 I.U. of porcine FSH per sheep was administered in eight decreasing doses twice daily starting four days after estrus was detected (Day 0) in group WS and 48 h before sponge removal in group S. A single i.m. dose of 125 μg of cloprostenol was administered on Day 6 after estrus in group WS to induce luteolysis. Sheep were naturally mated 24 h after cloprostenol injection or sponge removal. Seven days after mating, an inguinal laparotomy was performed and the number of corpora lutea (CL) recorded. Embryos were recovered surgically by flushing each uterine horn. A total of 38 fresh and 22 vitrified embryos were transferred in pairs into 3 groups of recipients seven days after estrus detection: fresh embryos from group S (S-F) (n = 9), fresh embryos from group WS (WS-F) (n = 10) and vitrified embryos from group WS (WS-V) (n = 11). Data on the number of corpora lutea (CL), recovered ova and embryos (OER), and quality 1-2 and 3 embryos (EQ(1-2), EQ(3)) per ewe were analyzed by ANOVA. Recovery (RR), fertility (FR) and quality 1-2 embryo (Q(1-2)R) rates per treatment were analyzed by a Chi Square analysis. A Chi Square analysis was also applied to pregnancy rate (PR), lambing rate (LR) and twinning rate (TR) of fresh and vitrified embryos in order to analyze embryo transfer results. Among all superovulation variables analysed, results show statistically significant differences in mean number of CL/ ewe (9.3 ± 3.9 vs 7 ± 3.2), RR (67% vs 80 %) and FR (100% vs 80%) (P < 0.05) between WS and S groups respectively. There were no significant differences in PR (78%, 70% and 82%), LR (67%, 60% and 59%) and TR (71%, 71% and 44.4%) among S-F, WS-F and WS-V groups respectively. In conclusion, it is possible to produce a good number of transferable embryos during natural oestrus avoiding the use of sponges.

Breast Scintigraphy with Breast-Specific γ-Camera in the Detection of Ductal Carcinoma In Situ: A Correlation with Mammography and Histologic Subtype

Ductal carcinoma in situ (DCIS) is a subtype of breast cancer encountered increasingly in clinical practice because of the widespread use of screening mammography. In the present study, we evaluated the usefulness of breast-specific γ-camera (BSGC) scintigraphy in DCIS identification, describing the scintigraphic findings and their correlation with mammography and histologic subtype. Methods: Thirty-three women, aged 41–81 y, with surgically proven DCIS were retrospectively reviewed. Before surgery, all patients underwent breast scintigraphy using a high-resolution semiconductor-based BSGC, starting 10 min after intravenous injection of 740 MBq of 99mTc-tetrofosmin. All patients had previously undergone mammography. A definitive histologic diagnosis was obtained in all cases after scintigraphy, and the scintigraphic findings were correlated with mammography and histologic subtype. Results: Mammography was positive in 30 of 33 patients (sensitivity, 90.9%), showing calcifications in 22 of 30 (73.3%), masses in 3 of 30 (10%), and masses plus calcifications in the remaining 5 of 30 (16.7%). Scintigraphy was positive in 31 of 33 patients (sensitivity, 93.9%), showing patchy irregular uptake in patients with calcifications and focal uptake in masses; sensitivity was higher in low- to intermediate-grade DCIS than in intermediate/high- and high-grade DCIS (100% vs. 91.3%), but the difference was not statistically significant. Two comedo-type DCIS (one 20-mm intermediate/high-grade and one 15-mm high-grade) with heterogeneously or highly dense breasts at mammography and one papillary low/intermediate-grade DCIS associated with Paget disease were true positive only at scintigraphy. Moreover, scintigraphy better assessed disease extent than did mammography in 5 additional patients. Two comedo-type DCIS (one 6-mm intermediate/high-grade and one 15-mm high-grade) were true positive only at mammography. The difference in sensitivity between scintigraphy and mammography was not statistically significant. The combined use of mammography and scintigraphy achieved 100% sensitivity. Conclusion: BSGC scintigraphy proved to be a highly sensitive diagnostic tool in the detection of DCIS, irrespective of histologic subtype, and with a scintigraphic pattern of uptake that correlated well with mammography findings. In our series, BSGC scintigraphy demonstrated a slightly higher sensitivity than mammography and a better assessment of local disease extent. Thus, BSGC scintigraphy should represent a useful adjunctive tool in breast cancer diagnosis.

Planar scintimammography and SPECT in neoadjuvant chemo or hormonotherapy response evaluation in locally advanced primary breast cancer

Conventional imaging procedures have proved of limited value in assessing tumor response to neoadjuvant chemotherapy in locally advanced primary breast cancer (LAPBC). We evaluated the usefulness of radioisotopic procedures comparing planar scintimammography (SM) to SPECT, monitoring pre-surgery neoadjuvant chemo- or hormonotherapy response in 32 LAPBC patients. In all cases, 99mTc-tetrofosmin conventional planar SM and SPECT were acquired by dual-head gamma camera with HR parallel hole collimators. In 15 cases, planar SM with small field of view high resolution dedicated breast camera (DBC) was also acquired. Scintigraphic data always correlated with histopathological findings. At surgery, 4/32 patients had pathological complete remission (pCR), while 28/32 patients had residual tumors. Both conventional planar SM and SPECT were true negative in 4/4 (100%) pCR patients, as was DBC in the only studied case. Conventional planar SM and SPECT detected residual tumors in 23/28 (82%) and in 25/28 (89.2%) cases, respectively. Both procedures missed 2 multifocal, scattered microscopic residues, only evidenced at DBC. Conventional planar SM also missed 3 further macroscopic residues (15-20 mm), while SPECT only one of these, a mucinous BC, in which DBC was not performed. DBC correctly classified all other 12 patients in whom the procedure was performed. Both conventional planar SM and SPECT proved useful diagnostic tools in monitoring neoadjuvant chemo/hormono therapy response in LAPBC with SPECT appearing more sensitive; however, our data, although in a limited number of cases, suggest that sensitivity can further be increased using high resolution DBC, especially in detecting microscopic residual tumor foci.

The use of embryonic cells in the treatment of osteochondral defects of the knee: an ovine in vivo study.

PURPOSE the aim of this study was to determine whether local delivery of embryonic stem-like (ESL) cells into osteochondral defects in the femoral condyles of sheep would enhance regeneration of hyaline articular cartilage. METHODS male ESL cells embedded in fibrin glue were engrafted into osteochondral defects in the medial condyles (ESL-M) of the left femur in 22 ewes. An identical defect was created in the medial condyle of the contralateral stifle joint and left untreated as a control (empty defect, ED). The ewes were divided into 5 groups. Four sheep each were euthanized at 1, 2, 6, and 12 months from surgery, and 6 ewes were euthanized 24 months post-implantation. To study the effect of varying loads on the long-term regeneration process, an identical defect was also created and ESL cell engraftment performed in the lateral condyle (ESL-L) of the left stifle joint of the animals in the 12- and 24-month groups. The evaluation of regenerated tissue was performed by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and fluorescent in situ hybridization (FISH) assays. RESULTS no significant differences were found between treated and control sites in the biomechanical assays at any time point. ESL cell grafts showed significantly greater macroscopic evidence of regeneration as compared to controls at 24 months after surgery; significantly better histological evidence of repair in ESL-M samples versus controls was found throughout the considered period. At 24 months from surgery there was significantly improved integration of graft edges with the host tissue in the ESL-M as compared to the ESL-L samples, demonstrating that load bearing positively affects the long-term regeneration process. CONCLUSIONS ESL cells enhanced the regeneration of hyaline cartilage. FISH confirmed that the regenerative tissue originated from ESL cells. CLINICAL RELEVANCE ESL cells are able to self-renew for prolonged periods without differentiation and, most importantly, to differentiate into a large variety of tissues.

The usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of residual tumors and axillary lymph node metastases in breast cancer patients following neoadjuvant therapy.

Single photon emission computed tomography (SPECT)/CT is emerging as a useful diagnostic tool in several oncological fields. In this prospective study, we assessed the usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of both residual breast tumors and axillary lymph node metastases following neoadjuvant therapy. Thirty-seven consecutive breast cancer patients scheduled to surgery following neoadjuvant therapy preoperatively underwent a Tc-99m-tetrofosmin SPECT/CT study, using a dual head gamma camera integrated with a x-ray tube for low-dose CT, including both breasts and axillary regions in the field of view. Within 1 week of SPECT/CT, all 37 patients had breast surgery with associated axillary lymph node dissection in 33/37 cases. At surgery, 31/37 patients had breast residues (microscopic in 4/31 cases and macroscopic in 27/31 cases). Axillary lymph node metastases were ascertained in 19/33 cases (N1mi: 2 cases, N1a: 8 cases, N2a: 6 cases, N2b: 3 cases). SPECT/CT sensitivity, specificity, and accuracy in detecting residual tumors were 87%, 100%, and 89.2%, respectively; the corresponding values in detecting axillary lymph node metastases were 36.8%, 92.8%, and 60.6%. SPECT/CT missed breast cancer residues in 4/31 patients, including 2 cases with microscopic residual disease. Moreover, lymph node metastases were missed in 12/19 patients (10/12 with pN1mi or pN1a metastases), all with lymph nodes with post-therapy fibrotic changes and small deposits of metastases. Tc-99m-tetrofosmin SPECT/CT proved a useful diagnostic tool in the detection and in the localization of residual breast tumors following neoadjuvant therapy. The procedure lacked in sensitivity in identifying axillary lymph node metastases, especially in patients with a limited lymph node involvement. According to our data, SPECT/CT may guide the surgeon to the most appropriate breast surgical treatment and to eventually select the most suitable axillary lymph node sampling (axillary lymph node dissection or sentinel node biopsy).

Cryogenic temperature protects biological material from gamma ray induced effects

1 Department of Human, Environmental and Natural Sciences, University of Urbino “Carlo Bo”, Italy 2 INFN Gran Sasso National Laboratories, Assergi (AQ), Italy 3 Laboratory and Image Diagnostic Department, San Salvatore Hospital, Pesaro, Italy 4 Agris-Sardegna, DIRPA (Agricultural Research Agency of Sardinia, Department of Animal Science) Reproduction Division, Sassari, Italy 5 ASLEM (Associazione Sammarinese Leucemie ed Emopatie Maligne), San Marino 6 Experimental Zooprophylactic Institute of Sardinia, Sassari, Italy 7 Health Physics Department, San Salvatore Hospital, Pesaro, Italy