Einat Even-Sapir

Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake

PURPOSEnTo assess the role of quantitative gallium citrate (Ga 67) single-photon emission computed tomography (SPECT) in differentiating lymphoma from benign hilar uptake, concentrations of Ga 67 in 29 sites of documented lymphoma and in 75 benign lesions were compared.nnnPATIENTS AND METHODSnOne hundred seven thoracic Ga 67 SPECT studies obtained in 101 consecutive lymphoma patients were reviewed. Fifty-nine studies detected Ga 67 uptake in the hilar and or mediastinal regions. Forty-eight studies showed no such abnormality. The concentration of Ga 67 in the thoracic lesions was measured using a quantitative SPECT technique and its nature was determined by correlation with computed tomographic (CT) scans and follow-up evaluation of the sites.nnnRESULTSnIn 20 of 59 abnormal studies (34%), there was lymphoma in the hilar and or mediastinal regions. In the remaining 39 abnormal studies (66%), Ga 67 uptake was benign. There were 29 sites of lymphoma and 75 benign lesions. The concentration of Ga 67 in lymphoma was significantly higher than in benign hilar uptake (13.2 +/- 5.4 %ID/mL x 10(-3) v 5.6 +/- 1.5 % injected dose (ID)/mL x 10(-3); P < .001). A concentration value of 8.3 %ID/mL x 10(-3) was found to best separate lymphoma and benign uptake, with a sensitivity of 90%, a specificity of 93%, a positive predictive value of 84%, and a negative predictive value of 96%.nnnCONCLUSIONnLymphoma and benign hilar uptake differ significantly in their concentration of Ga 67. The present study shows that quantitative Ga-67 SPECT reliably differentiates lymphoma and benign uptake.

Stress fractures and bone pain: are they closely associated?

The relationship between bone pain and stress fractures diagnosed by bone scintigraphy was investigated in military recruits during active training. In three patients pain appeared in the site of abnormal uptake 7-14 days after the bone scan in a previously asymptomatic site. One hundred and twenty-four sites of stress fractures were found in 64 patients; 32 (26 per cent) were asymptomatic. In 38 patients (59 per cent) there were multiple stress fractures; 32 (33 per cent) had asymptomatic stress fractures. Fifty-three per cent of the regions with abnormal uptake in the femur were painless, compared with 17 per cent in the tibia. The necessity for imaging all bones susceptible to stress fractures, even when asymptomatic, is stressed. It is suggested that diagnosis of stress fracture should be made when typical abnormal uptake appears on scintigraphy. Bone pain in such cases may be delayed.

In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors

Concentrations of bleomycin labeled with cobalt 57 (Co‐bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co‐bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient;s tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue.

The concentration of bleomycin labeled with Co‐57 in primary and metastatic tumors

The concentration over time of bleomycin labeled with Co‐57 was measured in 39 primary and metastatic tumor sites in 16 patients using a newly developed and validated single photon emission computed tomography (SPECT) method. There were nine primary tumors, 15 metastatic tumors, and five multifocal lymphomas. Co‐bleomycin concentrations also were measured in primary and metastatic B‐16 melanoma tumors in mice. In humans, metastases to lymph nodes (1.58 ± 0.51 %ID/ml × minutes) showed significantly higher (P < 0.01) tumor cumulative concentrations of Co‐bleomycin than metastases to liver, bone, lung, and brain (0.76 ± 0.20 %ID/ml × minutes). The cumulative concentrations of Co‐bleomycin in human lymphomas (1.1 ± 0.25 %ID/ml × minutes) also were significantly higher (P < 0.01) than the concentrations in human metastases other than lymph nodes. The cumulative concentration in cerebral metastases (0.65 ± 0.18 %ID/ml × minutes) was significantly lower (P < 0.05) than in noncerebral metastases (1.22 ± 0.53 %ID/ml × minutes). Primary tumors in humans showed higher concentrations of Co‐bleomycin than metastases, except for lymph nodes. In contrast with humans, murine metastases showed higher concentrations of Co‐bleomycin (6.20 ± 2.65 %ID/g) than primary tumors (2.94 ± 0.90 %ID/g) (P < 0.001). The concentrations of Co‐bleomycin in murine tumors that were affected by bleomycin were about three orders of magnitude higher than in human tumors. The results of this in vivo study document the differences in drug delivery of Co‐57‐labeled bleomycin to human primary and metastatic tumors and show differences in drug delivery between human and murine tumors.