Key elements of preparedness for pandemic coronavirus disease 2019 (COVID-19) in nuclear medicine units

European Journal of Nuclear Medicine and Molecular Imaging -     

Uptake of tritiated thymidine, deoxyglucose and methionine in three lung cancer cell lines: deoxyglucose uptake mirrors tritiated thymidine uptake.

[(18)F]-fluorodeoxyglucose and [(11)C]-methionine are tracers which are widely used in oncological positron emission tomography. This study has been designed to assess the deoxyglucose and methionine uptake behaviour in three cell lines from different lung cancer histotypes. Tracer uptake was compared with proliferative activity as determined by growth curves and tritiated thymidine uptake. Deoxyglucose paralleled thymidine in all cell lines, peaking in the lag phase, decreasing throughout the exponential phase, and reaching its minimum in the plateau phase. The correlation was statistically verified and Spearman's rho ranged from 0.79 to 0.99. The absolute methionine uptake was always highest and always peaked on day 2, followed by a quite rapid decrease. However, besides the delay in maximum uptake, methionine incorporation was also related to proliferation, although the statistical correlations were weaker. These results show for the first time a clear correlation between deoxyglucose uptake and cell proliferation in a model comparing tracer uptake in different growth phases. Although delayed, methionine uptake was also related to cell growth and its greater intensity could be of interest for clinical use.     

Laboratory tests for neuroendocrine tumours.

Neuroendocrine tumours (NETs) often have a good prognosis and have peculiar biological characteristics, among which the ability to produce and release biologically active substances. Hypersecretion of hormones, biogenic amines or growth factors often cause severe syndromes that are very debilitating. Now sensitive assays for the measurement of these substances have been developed and this has improved the possibility of patient follow-up by means of in vitro examinations. The decision about which in vitro examination to be utilised for NET management is very difficult because of the NET low incidence, the very large number of measurable hormones, the difficulty or low patient compliance for some diagnostic tests. In this review we describe the most useful laboratory tests for determining the diagnosis of NET, their prognostic significance and the clinical value of specific marker evaluation in the follow-up of the NET patient. Particular consideration has been given to biomarkers for gastroenteropancreatic and sympatho-adrenal system tumours and for prostate and breast cancers with neuroendocrine differentiation.     

Scintigraphic documentation of an improvement in hepatobiliary excretory function after treatment with ursodeoxycholic acid in patients with cystic fibrosis and associated liver disease.

We have previously documented that ursodeoxycholic acid exerts a beneficial effect on liver function and bile acid metabolism in patients with cystic fibrosis. We hypothesized that the mechanism of action may be related in part to the choleretic properties of the administered bile acid. We therefore compared hepatobiliary scintigraphic images obtained before and 1 yr after initiation of ursodeoxycholic acid therapy to document an improvement in bile flow in 13 patients with cystic fibrosis and hepatobiliary involvement. Before therapy, hepatobiliary scintigraphy documented biliary stasis with retention of the isotope in intrahepatic and extrahepatic bile ducts in nine patients; during therapy, duct dilatation decreased substantially in eight patients, with decreased intrahepatic retention and more rapid biliary outflow of the tracer. The time of appearance of isotope in the intestine decreased (from a mean of 36.9 +/- 17.8 min to 18.8 +/- 9.0 min; p less than 0.01) in all patients in whom it had been abnormal, and the half-time of hepatic washout decreased from a mean of 35 +/- 20.7 min to 26 +/- 15.6 min (p less than 0.05). During ursodeoxycholic acid administration enrichment of bile was achieved, with the mean ursodeoxycholic acid percent composition increasing from 5.8% +/- 2.9% to 35.7% +/- 8.5%. Ursodeoxycholic acid became the predominant bile acid in serum. Liver function improved in all 10 of the patients with abnormal values at baseline. We conclude that hepatobiliary scintigraphy is of value in monitoring the therapeutic responses of cystic fibrosis patients with liver disease to ursodeoxycholic acid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

Tissue polypeptide antigen and carcinoembryonic antigen in colon tumors: serum levels and immunohistochemical localization

Patients with malignant and benign colon disease (59 colon cancer and 96 polyps) were studied by means of tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) tests. The evaluation of the circulating levels of the markers showed that the overall sensitivity for the TPA test was 57.6% and for the CEA test was 55.9%. Their specificities were 89.5% and 94.7%, respectively. The analysis of results indicated no considerable difference between CEA and TPA in detecting individuals with malignant diseases. There was only a slight difference in Dukes stages: in stages A and B, TPA sensitivity was higher than CEA sensitivity. On the contrary, in the group of patients with polyps, more false-positive results were obtained with the TPA test than with the CEA test. Immunohistochemical studies on the small group of patients (12 colon cancers) allowed us to evaluate the relationship between the staining positivity for the anti-TPA and anti-CEA antibodies and the circulating levels of the markers. The staining in some cases was not correlated either with the stage of cancer or the circulating TPA or CEA levels. This fact further shows the need to investigate the mechanism that determines the blood levels of many tumor markers. All the specimens examined were positive for TPA and CEA staining, but they were composed of varying proportion of positive and negative tumor cells. The degree of positivity was frequently variable not only between the specimens but also within the same specimen.     

Pathological diagnosis and tumor markers

Pulmonary and digestive neuroendocrine tumors (NETs) are a group of neoplasms whose incidence and prevalence has been constantly increasing over the last years thanks to the significant improvements in instrumental diagnostic techniques. Because NETs are extremely heterogeneous a correct histopathological diagnosis is essential for appropriate treatment. More specifically, the histopathological diagnosis of NETs can be regarded as a multistep: identification of the neuroendocrine nature of the neoplasm, determination of tumor grading; identification of unknown primary. Laboratory biomarkers for the study of gastroenteropancreatic neuroendocrine tumors include both specific markers and non-specific or general markers. At the moment, chromogranin A is the best available and most frequently used biomarker for the diagnosis of NETs, offering the highest overall sensitivity. CgA has also demonstrated some utility in the assessment of response to treatment and as indicator of tumor recurrence.     

Recombinant human thyrotropin (rhTSH) in the follow-up and treatment of patients with thyroid cancer

The follow-up of thyroid cancer is based on the detection of residual and recurrent thyroid carcinoma. This is traditionally done by means of measurements of serum thyroglobulin (Tg) combined with various imaging techniques (131I-whole body scan, ultrasound and other modalities). Tg serum levels and the uptake of 131I on a whole body scan (WBS) depend on TSH stimulation, which in thyroidectomized patients can be obtained either by withdrawal of thyroid hormone treatment (thyroxine) or by administration of exogenous TSH. At present exogenous human TSH is obtained by means of recombinant DNA technology, (recombinant human TSH (rhTSH), Thyrogen). Even if the administration of rhTSH and withdrawal of thyroid hormone are not completely equivalent, the use of rhTSH has already entered the clinical routine (rhTSH Tg test and rhTSH WBS) because with rhTSH the morbidity and discomfort associated with the withdrawal of thyroid hormone can be avoided. At a recent International Consensus Conference on the follow-up of differentiated thyroid carcinoma it was proposed to carry out only Tg measurement after rhTSH stimulation; moreover, it was stated that 131I whole body scan has to be discouraged in patients submitted to radical surgery and radioiodine ablation with no clinical evidence of residual tumor and with undetectable levels of Tg during hormonal suppression of TSH. Similar strategies in this respect tend to eliminate the 131I WBS and propose only the rhTSH Tg test combined with head and neck ultrasound (US). This is still a matter of debate, also because it is not valid for all risk groups and not all patients undergo the same clinical management (radical surgery or not, thyroid ablation with 131I or not). However, the availability of rhTSH will definitely change the management of papillary and follicular thyroid carcinoma, also with regard to iodine treatment. In fact, rhTSH can be used during radioiodine treatment to enhance the 131I uptake by the cancer cells in particular groups of patients. Patients who could benefit from this approach can be divided into three subgroups: 1) patients in whom thyroxine withdrawal may be dangerous because of the effects of long-term TSH stimulation on the tumor mass (brain metastases, vertebral metastases, presence of neurological signs, heart diseases); 2) patients affected by tumors with marked biological aggressiveness and a low iodine uptake (variants of follicular carcinoma, insular carcinoma, tall and columnar cell variants of papillary thyroid carcinoma, Hürthle cell carcinoma); 3) patients with hypothalamic-pituitary alterations. The potential efficiency of rhTSH in radiometabolic treatment is an important issue that has been studied in a limited number of patients, but is worthy of further investigations in large perspective. A recent clinical prospective trial has been proposed by the Thyroid Cancer Study Group of the Istituto Nazionale Tumori and is now ongoing.     

TSH suppression as a possible means of protection against hypothyroidism after irradiation for childhood Hodgkins lymphoma

Hypothyroidism remains a common late effect after irradiation of the neck/mediastinum for Hodgkins lymphoma (HL). We evaluated the protective effect of TSH suppression during neck/mediastinum irradiation. From 1998 to 2001, 14 consecutive euthyroid children were given, before and until the end of their radiotherapy on neck/mediastinum, L-thyroxine at TSH-suppressive doses. The 14 patients had adequate TSH suppression during irradiation in 8, inadequate in 6. The 8-year hypothyroidism-free-survival after irradiation was 75 ± 15% for the former group, 0% for the latter (P = 0.009). TSH suppression could have a protective effect on thyroid function as shown in a small group of patients with HL.