Joachim Kropp

Prognostic value of positron emission tomography in the evaluation of post‐treatment residual mass in patients with Hodgkin's disease and non‐Hodgkin's lymphoma

The prognostic value of 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post‐treatment residual masses in patients with Hodgkins disease (HD) or non‐Hodgkins lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post‐therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG‐PET was performed separately for HD and NHL. Patients with a PET‐positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62·5% (5/8 patients), whereas patients with PET‐negative residual mass (SUV ≤ 3·0) showed a recurrence rate of 4% (2/50 patients, P = 0·004). A positive FDG‐PET study correlated with a significantly poorer progression‐free survival (P < 0·00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG‐PET is a suitable non‐invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.

High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

PURPOSE Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. CONCLUSION Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.

Ventilation/perfusion lung scintigraphy: what is still needed? A review considering technetium-99m-labeled macro-aggregates of albumin

Lung perfusion scintigraphy (LPS) with technetium-99m-labeled macro-aggregates of albumin (Tc-99m-MAA) is well established in the diagnostic of pulmonary embolism (PE). In the last decade, it was shown that single-photon emission computer tomography (SPECT) acquisition of LPS overcame static scintigraphy. Furthermore, there are rare indications for LPS, such as preoperative quantification of regional lung function prior to lung resection or transplantation, optimization of lung cancer radiation therapy, quantification of right-left shunt, planning of intra-arterial chemotherapy, and several rare indications in pediatrics. Moreover, LPS with Tc-99m-MAA is a safe method with low radiation exposure. PE can also be diagnosed by spiral computer tomography (CT), ultrasound, magnetic resonance angiography, or pulmonary angiography (PA, former gold standard). The present review considers all these methods, especially spiral CT, and compares them with LPS with respect to sensitivity and specificity and gives an overview of established and newer publications. It shows that LPS with Tc-99m-MAA represents a diagnostic method of continuing value for PE. In comparison with spiral CT and/or PA, LPS is not to be defeated as mentioned also by the most actual Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II reports. This applies in particular to chronic or recurring embolisms, whereas currently spiral CT may be of greater value for major or life-threatening embolisms. At present, LPS cannot be replaced by other methods in some applications, such as pediatrics or in the quantification of regional pulmonary function in a preoperative context or prior to radiation therapy. LPS still has a place in the diagnostics of PE and is irreplaceable in several rare indications as described earlier.

Diagnostic Value of 18F-FDG Positron Emission Tomography for Detection and Treatment Control of Malignant Germ Cell Tumors

Introduction: The role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is currently under evaluation in urologic oncology. The aim of the present study was to investigate the use of [18F]FDG positron emission tomography ([18F]FDG-PET) in the detection and treatment control of malignant germ cell tumors compared to computed tomography (CT). Materials and Methods: Thirty-two PET studies and CT scans were carried out in 23 patients with histologically proven germ cell tumors (10 seminomas, 12 non-seminomatous germ cell tumors (NSGCT), 1 unclassified serologic recurrent disease) Lugano stage I–III. The scans were done either after initial diagnosis (n = 21) and/or within 3–45 days after chemotherapy was completed (n = 11). PET and CT were validated either by histology (n = 7) or clinical follow-up of 6–11 months after the last PET study has been performed (n = 16). Sensitivity, specificity, accuracy, positive and negative predictive values were determined for PET and CT. Differences between PET and CT for parameters of diagnostic value were evaluated by χ2 test. Results: Although not statistically significant, the sensitivity, accuracy and negative predictive value were higher for PET than for CT with respect to the detection of metastatic infradiaphragmatic and supradiaphragmatic lesions after initial diagnosis. The specificity and positive predictive value of PET and CT were comparable. After chemotherapy, PET was found to be significantly superior in specificity and accuracy compared to CT with respect to infradiaphragmatic lesions (p < 0.05). False-positive PET findings in supradiaphragmatic lesions after chemotherapy occurred in the case of inflammatory processes and resulted in a loss of specificity and accuracy compared to CT (p < 0.05). Conclusions: These preliminary results demonstrate [18F]FDG-PET to be a useful diagnostic tool for the initial staging and treatment control in patients with germ cell tumors. Possible advantages compared to CT, however, are as yet not clearly defined. The possibility of false-positive PET findings due to reactive supradiaphragmatic inflammatory processes early after chemotherapy have to be considered.

Rhenium-188-HEDP in the Palliative Treatment of Bone Metastases

INTRODUCTION Rhenium-188-HEDP (188Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of bone pain due to metastases. As a product of a 188W/188Re generator it is convenient for clinical use. With a short physical half life of 16.9 hours and a maximal beta-energy of 2.1 MeV, it is suitable for therapy. METHODS We investigated the influence of 188Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 15 patients. All patients were interviewed using standardized questions before, and 1, 2, 3, 4, 8, and 12 weeks after therapy. Blood samples were drawn weekly for 12 weeks, and a blood count was performed. Patients underwent gamma camera imaging to determine the radionuclide accumulation 4, 20, and 28 hours after therapy. The patients were treated with 1600 to 3459 MBq of 188Re-HEDP. RESULTS Patients showed an improvement of the Karnofsky performance index from 74 +/- 8% to 84 +/- 11% 12 weeks after therapy. This improvement was statistically significant (p = 0.001). Eighty percent of the patients described pain relief and reduction of analgesics. Twenty percent of the patients could discontinue their analgesics. Mean platelet count decreased from (284 +/- 84)*10(3)/microliter to (205 +/- 62)*10(3)/microliter, and mean leukocyte count from (7.5 +/- 1.5)*10(3)/microliter to (5.9 +/- 2.1)*10(3)/microliter after therapy. The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p = 0.021 and p = 0.094). Prostate specific antigen decreased from 95 +/- 83 ng/ml to 41 +/- 21 ng/ml, the difference was not statistically significant (p = 0.443). The bone accumulation 4, 20, and 28 hours after therapy was 1.3 +/- 0.5%, 0.6 +/- 0.3%, and 0.45 +/- 0.2% of the injected dose of a single metastasis, and 57 +/- 17%, 15.5 +/- 2% and 11 +/- 3% in the whole body, respectively. The effective half-life of 188Re-HEDP was 15.3 +/- 3.0 hours in the bone metastases, and 11.4 +/- 2.8 hours in the whole body. This corresponds to a residence time of 0.22 +/- 0.25 hours in the bone metastases, and of 10.54 +/- 2.59 hours in the whole body. CONCLUSION In a small patient population, 188Re-HEDP therapy for bone pain palliation was effective and was associated with minimal toxicity.

Incorporation of radioiodinated IPPA and BMIPP fatty acid analogues into complex lipids from isolated rat hearts

Heart lipids were extracted by the Folch technique from Langendorff-perfused rat hearts after administration of 15-(p-[131I]iodophenyl)pentadecanoic acid and 15-(p-[125I]iodophenyl)-3-R,S-methylpentadecanoic acid. Techniques utilizing successive high performance liquid chromatographic (HPLC) analyses have been developed for the evaluation of the uptake of the tracers into neutral lipids and phospholipids of the rat hearts. Phospholipids were separated on a SiO2 column eluted with a gradient of acetonitrile/water (97.5/2.5) and acetonitrile/water (85/15) followed by separation of the neutral lipids on a C-18 reversed phase column with a gradient consisting of acetonitrile and 2-propanol/hexane (60/40) containing 1 N H2SO4 (5 microL/100 mL). Both tracers show the incorporation into the expected major lipid classes.

Single photon emission tomography imaging of myocardial oxidative metabolism with 15-(p-[123I]iodophenyl) pentadecanoic acid in patients with coronary artery disease and aorto-coronary bypass graft surgery

A total of 29 patients with coronary artery disease (CAD) were investigated with 15-(p-[123I] iodophenyl)pentadecanoic acid (123I-IPPA) and sequential single photon emission tomography (SPET). Of these, 19 were studied after aorto-coronary bypass graft surgery. Some 13 patients without evidence of CAD served as a control group. Two SPET studies (early and late) were carried out within 45 min after intravenous administration of 200 MBq 123I-IPPA at peak sub-maximal exercise. Semi-quantification of uptake (related to perfusion) and turnover (linked to metabolism) was obtained by segmental comparison of oblique slices. Taking coronary arteriography as the “gold standard”, 123I-IPPA scintigraphy had the following figures of merit for sensitivity and specificity in the diagnosis of CAD: for the left anterior descending artery territory 93% and 95%, for the left circumflex artery region 96% and 92%, and for the right coronary artery territory 77% and 92%, respectively. In all, 90% of the reperfused myocardial segments showed an improvement of uptake. Of these, 61% exhibited increased turnover after revascularization and 39% had pathologic turnover and thus a dissociation of improvement of perfusion and oxidative metabolism after surgery.

Tc-99m labeled monoclonal antibodies against granulocytes (BW 250/183) in the detection of appendicitis.

Scintigraphy with Tc-99m labeled antigranulocyte antibodies (BW 250/183 MoABs) was performed in 32 patients with suspected appendicitis. Abdominal imaging (planar/SPECT) was performed 2 hours after injection of the tracer. All patients also had surgery and a histologic examination of the resected tissue. Of the patients, 17 suffered from “acute appendicitis” and 12 had right positive scans (sensitivity = 70.6%). In 15 patients, acute appendicitis could have been ruled out, and in 11 of these cases the scan was true negative (specificity = 73.3%). The overall accuracy was 71.8% (23/32 cases). The use of Tc-99m antigranulocyte MoABs may overcome the problems associated with the Tc-99m HMPAO granulocyte and ln-111 oxine approaches, which include nonspecific intestinal activity or the lack of timeliness. The use of Tc-99m labeled antigranulocyte antibodies is suitable as an emergency procedure and may play a role in the management of patients with suspected appendicitis.

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.

Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues.

PurposeIn an effort to develop 99mTc-labelled fatty acids (FAs) for myocardial metabolism and flow imaging, several 99mTc analogues according to the ‘3+1’ and the ‘4+1’ mixed-ligand approach were synthesized and myocardial extraction was evaluated in non-working isolated guinea pig hearts. An example of biodistribution patterns in guinea pigs was determined by using one FA analogue. MethodsThe coordination moieties contain a +5, respectively +3, oxidation state metal core attached to the end position of a FA chain. FA complexes of the ‘3+1’ and the ‘4+1’ mixed-ligand type were prepared and investigated using the isolated heart model. To estimate the diagnostic value of the analogue 99mTc-FAs, the biodistribution of one well-extracted FA was evaluated. ResultsThe ‘4+1’ FA compounds achieved the highest uptake rates of all the technetium FAs investigated. In particular, the ‘4+1’ 99mTc-C11-FA achieved at least a 2-fold higher ventricular extraction of the applied activity than the established control tracers including ω-(p-[123I]iodophenyl)pentadecanoic FAs (BMIPP and IPPA) and 99mTc-MIBI. Furthermore, the ‘4+1’ dodecanoic FA derivative and the thiadodecanoic FA derivative showed an extraction comparable to established 123I-labelled tracers. Biodistribution experiments performed for the thiadodecanoic FA derivative indicated a good heart/blood and heart/lung ratio and also a high uptake in the liver. In contrast, ‘3+1’ 99mTc complexes showed a low myocardial extraction rate. Nevertheless, the differentiation in the extraction profile, which depends on the FA chain length and structure, indicates a specific heart uptake of these 99mTc-labelled FA derivatives as well. ConclusionsThe excellent extraction rates found for ‘4+1’ 99mTc-FAs indicate possibly promising structures for innovative myocardial tracers.